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Sonika Sethi Department of Chemistry, School of Engineering and Sciences, GD Goenka University, Gurgaon, 122103, Haryana, India

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Jürgen Martens Institut für Chemie, Carl von Ossietzky Universität Oldenburg, D-26129, Oldenburg, Germany

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Ravi Bhushan Institut für Chemie, Carl von Ossietzky Universität Oldenburg, D-26129, Oldenburg, Germany
Department of Chemistry, Indian Institute of Technology Roorkee, Roorkee, 247667, India

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Abstract

Indapamide (Indp) and certain other diuretics have been abused in sports, therefore, having sensitive methods for its detection and assay in biological fluids (whole blood, plasma, serum, and urine) is of significant importance. The racemic mixture of Indp is being used as an active pharmaceutical ingredient among other commonly prescribed diuretics. The regulatory authorities and pharmaceutical industries demand analytical methods for successful enantioseparation of such molecules. The paper presents a critical overview of the scientific issues of the application of contemporary techniques involving various chromatographic approaches (with liquid or supercritical fluid as mobile phases) and capillary electrophoresis and method development, for drug screening, assay, bioequivalence studies and enantioseparation of indapamide with their results. It also covers the historical developments that led to significant breakthroughs in research and concise evaluations of research in the area.

Different types of chromatographic methods (HPLC, CEC, SFC etc) discussed herein provide an insight and a choice to select a method to (i) screen Indp for drug abuse, (ii) separate, isolate and quantify the enantiomers of Indp and (iii) investigate their pharmacokinetics as markedly different species and not as a total drug. The article evaluates the field's status with a broad base and practical oriented approach so that the underlying principles are easily understood to help chemists and non-specialists gain useful insights into the field outside their specialization and provide experts with summaries of key developments. To the best of authors' knowledge there has been no attempt to review such methods for analysis of Indp and this is the first report of its kind.

Abstract

Indapamide (Indp) and certain other diuretics have been abused in sports, therefore, having sensitive methods for its detection and assay in biological fluids (whole blood, plasma, serum, and urine) is of significant importance. The racemic mixture of Indp is being used as an active pharmaceutical ingredient among other commonly prescribed diuretics. The regulatory authorities and pharmaceutical industries demand analytical methods for successful enantioseparation of such molecules. The paper presents a critical overview of the scientific issues of the application of contemporary techniques involving various chromatographic approaches (with liquid or supercritical fluid as mobile phases) and capillary electrophoresis and method development, for drug screening, assay, bioequivalence studies and enantioseparation of indapamide with their results. It also covers the historical developments that led to significant breakthroughs in research and concise evaluations of research in the area.

Different types of chromatographic methods (HPLC, CEC, SFC etc) discussed herein provide an insight and a choice to select a method to (i) screen Indp for drug abuse, (ii) separate, isolate and quantify the enantiomers of Indp and (iii) investigate their pharmacokinetics as markedly different species and not as a total drug. The article evaluates the field's status with a broad base and practical oriented approach so that the underlying principles are easily understood to help chemists and non-specialists gain useful insights into the field outside their specialization and provide experts with summaries of key developments. To the best of authors' knowledge there has been no attempt to review such methods for analysis of Indp and this is the first report of its kind.

1 Introduction

Indapamide (Indp, Fig. 1) is a medium efficiency diuretic drug. From among the different groups of diuretics based on their pharmacological properties, Indp is a thiazide-related diuretic. Indp is excreted unchanged to the extent of 7% or due to the hydrolysis of its >C=O or when glucuronic acid or sulphate are colligated in the living system [1]. Indp is known (i) to drastically reduce the weight, (ii) to reduce the concentration of other doping reagents in urine so that these are not detected (because either the urine volume is increased or the urinary pH is altered). For these reasons Indp becomes a drug of abuse in international athletics events (e.g., to qualify for a lower Olympic lifting category by the participants). Therefore, the use of diuretics, including Indp, was declared illegal by the International Olympic Committee (IOC) with effect from the Olympics of 1988. So, for the scientific community it is a challenge to develop analytical methods for assay and detection of different individual diuretic agents in the biological fluids for bioequivalence studies and drug screening purposes which is highly desirable.

Fig. 1.
Fig. 1.

Structures of (R)- and(S)-Indp

Citation: Acta Chromatographica 36, 2; 10.1556/1326.2023.01123

By the same token, and in view of the mandatory policies of the regulatory authorities worldwide (in the U.S., in European Union, Canada, and Japan) the pharmaceutical industry demands analytical methods and data for successful enantioseparation (and control of enantiomeric purity) of non-polar or volatile racemates and enantiomeric mixtures of all kinds of active pharmaceutical ingredients (APIs) since it has been established that the human/animal body is chirally selective and the two enantiomers of a chiral drug may show different pharmacological behaviour and toxicity [2, 3]. Indp is a thiazide like diuretic, yet there are few studies/reports on the methods used or developed for enantioseparation, determination and bioassay of Indp and its two enantiomers.

This review, thus, discusses such aspects of Indp. To the best of authors' knowledge there has been no attempt to review such methods for analysis of Indp. The methods discussed herein include, direct chiral separation by high performance liquid chromatography (HPLC), capillary electrochromatography (CEC) and supercritical fluid chromatography (SFC). This is the first report wherein authors have tried to compile and compare the results of the three methods of enantioseparation of Indp. The overall literature reports on enantioseparation of Indp are scanty. It cannot be claimed that it has included all the references on detection, assay, and bioequivalence studies and drug screening; however, it serves a good source to know the literature on the subject with a briefing of methods and critical commentary.

2 Indapamide

Indp (Fig. 1) is chemically 3-(amino sulfamoyl)-4-chloro-N-(2, 3-dihydro-2-methyl-1H-indol-1-yl) benzamide (with Mol. Wt = 365.8 g mol−1). The structural features of the molecule include the presence of a lipid-soluble methylindoline moiety, and only one sulfonamide group as a polar sulfamoyl chlorobenzamide moiety. The absence of thiazide ring system makes it different from the thiazide group of diuretics. Indp has antihypertensive properties, and is also used in the treatment of oedema, heart attack and other heart related issues. In vitro and in vivo data established that Indp reduces blood pressure in acute and chronic conditions of various forms of hypertension [1] which may be genetic or non-genetic in nature. It is white odourless crystalline powder which can be dissolved in ethanol, MeOH, acetic acid and other organic solvents. It is marketed in single pharmaceutical dosage (in the form of immediate release or sustained release tablets) as well as combination drug form [4]. Indp inhibits the passage of Ca2+(Na+ and K+) ions across membranes leading to widening of arteries thereby causing enhanced blood flow to the areas lacking oxygen and thus reduction in blood pressure via peripheral and arteriolar resistance [5]. There occurs a synergistic effect of Indp in combination with ACE inhibitors or other antihypertensive drugs [6]. It was observed that high Indp concentrations enhance the overall effect in species-dependent manner [7] and it was considered as one of the beneficial properties of Indp. Indp was patented in 1968 and during 2013–2019 it was among the top 325 drugs of prescription.

3 Bioequivalence study and drug screening

Literature search reveals separation and determination of Indp in biological fluids by chromatographic methods, supplemented with other advanced techniques (like MS). This is briefly discussed below in order to present a sketch (and not an all-encompassing literature) of the applications of contemporary techniques used to develop the methods for analysis and assay of Indp indicating historical development, as well, in the area.

As early as in 1982, Choi et al. [8] reported an HPLC method for analysis of Indp in human blood and urine because in in vitro studies Indp was found to be absorbed by the red cells within 5 min. There was adopted an internal standard approach (with sulphanilamide) and a RP column having dimethyl-octadecylsilane groups bonded to Zorbax 5 μm silica particles followed by an end-capping reaction with trimethylsilane was used for plasma samples and a LiChrosorb C18 column (10 μm particle size) was used for blood and urine samples with detection at 241 nm in both cases, the LOD values were 50 ng mL−1 for blood and urine, and 25 ng mL−1 for plasma. The authors claimed that this method was being successfully used in different laboratories for the assay of human clinical samples. Brent Miller et al. [9] used a method involving single-step liquid-liquid extraction (LLE) at pH 6.6 with diethyl ether, and glipizide (a sulphonyl urea with pKa of 5.9) as the internal standard, and C18 column (L × i.d., 150 × 4.6 mm, in-house prepared) for analysis of Indp specifically in human blood; it provided LOQ of 10.0 ng mL−1 and required overall run time of fourteen minutes [9]. This method was five times more sensitive than that reported by Choi et al. [8] and was applied to ascertain the pharmacokinetics of a single 2.5 mg dose of Indp in humans (ten healthy donors) over a 48 h period.

Amperometric detection was applied for quantitative determination of Indp in urine (of some healthy volunteers and patients of hypertension) by HPLC [10] and pharmaceutical tablets (using Ultrasphere ODS column, L × i.d., 75 × 4.6 mm, and 3 μm). The clean-up of urine sample was done by solid-liquid extraction approach which was compared with LLE procedure. MeCN-H2O (45:55, v/v) with 5 mM phosphate buffer (pH of 4.0) at 1.0 mL min−1 was used as the mobile phase (MP) and the supporting electrolyte was the same phosphate buffer. The maximum sensitivity for Indp was achieved at 1200 mV of the oxidative potential. The LOD was 01 ng mL−1 which was lower than the earlier reports (showing 25 ng mL−1 by UV detection and LLE) of Pietta et al. [11] and Choi et al. [8]. The solid-liquid extraction involving cartridge conditioning, sample purification by removing interferences [10] and elution of Indp followed by LLE as the clean-up step was very cumbersome and time taking though the percentage recovery was 88.3 ± 5.6.

One step LLE was found successful for RP-HPLC/UV assay of Indp in samples of whole blood by Hang et al. [12]. The method was applied for pharmacokinetic and bio-equivalence in-vivo investigations of two formulations of Indp by taking blood from Chinese male and healthy volunteers. Indp was extracted with diethyl ether with glipizide as internal standard. Phosphate buffer (prepared by dissolving 3.5 mL Et3N, 2 g potassium dihydrogen phosphate and 3 mL phosphoric acid in one litre water)-MeCN (aq 40%)-MeOH (55:45:5, v/v) was the MP in isocratic mode using a column with C18 stationary phase for separation of Indp.

In 1996, Ventura and Segura [13] presented a review of screening methods used for detecting the presence of diuretics in urine for meeting the objective of doping control requirements. It included 116 references reported during 1980–1995 to cover sample preparation for LC analysis with particular attention on derivatization for GC, for screening and confirmation of specific compounds. LC approaches used C18 type stationary phases, phosphate or acetate buffers as MPs and MeOH or MeCN were used as organic modifier. Detection was generally made in UV range (at 220, 273, or 328 nm) with diode-array or fluorescence detectors were selected depending upon the structure of the drug. For several years, GC-MS was used by the anti-doping laboratory, Rome, accredited by IOC, to perform the tests for different diuretics as their methyl derivatives; when the sports authority required the test report of the urine of athletes the GC method via derivatization could not compete with other rapid methods because it required at least 3 h of incubation period at 70 °C. The methylation (using methyl iodide) of several polar diuretic drugs remained the most common procedure [14] with the use of GC-MS simply as a screening method. Extractive alkylation was applied as the simplest process with extraction and derivatization completed in one step [15]; the method could provide results for nearly 3,000 samples in less than thirty days during the Olympic Games of Sydney in 2000.

In 2003, Amendola et al. [16] applied microwave irradiation (MWI) for preparing corresponding methyl derivatives, instead of by direct thermal heating; it took overall 10 min instead of 3 h for the derivatization step and there was observed significant improvement in the yields, for about 19 diuretics under study including Indp, and LOD values analysed by GC-MS in selected ion monitoring (SIM) mode. The method comprised of pretreatment steps (extraction, pre-concentration and derivatization of urine samples with CH3I in presence of K2CO3) before chromatography. With this process the LOD for Indp was 40 μg L−1 while the yield was 2.5 times more due to MWI in comparison to the normal heating approach. The authors claimed [16] that the assay results obtained at the anti-doping laboratory, Rome in the period January–June 2002 for the derivatives prepared by MWI or by normal heating method were unambiguously in agreement using phenyl-methyl silicone column (L × i.d. 18 m × 0.2  mm, 0.33 μm film).

In the same year 2003, Zendelovska et al. [17] used HPLC with C8 column and MeCN-TEA (0.1%) in water (37:63, v/v) as the MP. The pH of TEA solution was adjusted to 3.5 using a small amount of conc-o-phosphoric acid. A manual solid-phase extraction (SPE) vacuum manifold was employed for preparation of sample from biological fluids (that required two step clean-up and pre-treatment with diazepam as the internal standard). There was no interference for the Indp and internal standard peak positions for detection of Indp at 240 nm. The recovery was nearly 80% though the method required large amount of whole blood and repeated elution with different volumes of MeOH. Thus, the whole procedure was extensive. The LOD values were 4.0 ng mL−1 and 20.0 ng mL−1 for human serum and blood samples, respectively.

The methylation method was considered to have difficulties in derivatization of certain diuretics besides the toxic nature of CH3I. To avoid such derivatization, LC/MS were used for the separation and identification, for example, (i) in 2002, Deventer et al. [18] presented a method for the screening of 18 diuretics including Indp in human urine using HPLC coupled with MS (LC/MS/MS) without a preliminary derivatization step; it required two liquid-liquid extractions with ethyl acetate and separation occurred in a few minutes using Nucleosil C18 column and acetic acid (1%) and MeCN in gradient mode (of 30 min run time) with an LOD of 50 ng mL−1. The method was simpler in comparison to the previous reports [19, 20] using HPLC/UV which required an additional step of clean up (i.e., extraction with acid followed by treatment with lead acetate). Besides, it was found very selective as there was no interference with the presence of other doping agents like β-adrenolytics, corticosteroids etc. Mefruside (a benzene disulfonamide derivative of the thiazide diuretics) was selected as internal standard because more than 99% of it remained as unchanged drug after its administration to humans [21], and (ii) Goebel et al. [22] in 2004, collected urine samples from athletes and reported a method for routine detection of 35 diuretics including Indp. Samples were prepared by automated SPE and the recovery was greater than 80%; analysis was performed using HPLC-electrospray ionisation tandem MS. The LOD of 100 ng mL−1 was much below the limit set by the IOC. It replaced the earlier method based on extractive alkylation [23, 24] and GC-MS and the other method in which methylation was assisted by MWI after extraction [25]. Besides, the method was successful for investigating over 6,000 samples of urine in 12 months with only one HPLC column while the GC-MS method required four machines to achieve higher throughput.

In 2005, Albu et al. [23] performed bioequivalence studies to assay Indp, in plasma, based on single and multiple doses of controlled release tablets. Indp and internal standard were isolated from plasma by LLE in t-butyl methyl ether in one step. The recovery yield was more than 80%. The isolation of Indp from plasma was not adversely affected by matrix effect. Indp is a weak acid (having pKa 8.8), therefore, addition of phosphate buffers in the aq phase to modify pH to 3, 7, or 10 did not alter the recovery to a noticeable change. The column was RP-C18 and MeOH-aq. 0.1% HCOOH (42.5:57.5, v/v) was the MP flowing at 0.8 mL min−1 in isocratic conditions, it was followed by application of atmospheric pressure electrospray interface (AP-ESI) in SRM mode for transfer to an ion trap analyzer. The LOQ was 01 ng mL−1. It was observed that retention and resolution were not affected by a change in concentration of HCOOH in the aq part of MP while the detection sensitivity was reduced ten times by the addition of TFA. The overall procedure was lengthy in terms of sample preparation (by extraction with organic solvent and evaporation), followed by loading onto the HPLC column and detection by tandem mass spectrometry. However, the method demonstrated a high throughput characteristic for complimentary application of HPLC with mass spectrometry, particularly because UV detection was not found to be sufficiently selective and sensitive to assay Indp in biological fluids. Serum is the liquid that remains after the clotting of blood while plasma is the liquid that contains anticoagulant agents added to prevent clotting.

Quantification of Indp in human whole blood was achieved [24] using methyl tert-butyl ether for LLE (along with carbamazepine as internal standard) and C18 column and MeCN–propan-2-ol–0.1% TEA in water (35:5:60, v/v) for separation. TEA was adjusted to pH 3.75 by adding 85% phosphoric acid. Detection was in UV at 245 nm. The method was successful to ascertain pharmacokinetics of a single 2.5 mg dose of Indp in 20 Chinese healthy volunteers in a balanced open random, two-period crossover (over 60 h) study using only 500 μL sample aliquots [24]. The HPLC method for assay of Indp in human whole blood reported by Brent Miller et al. [9] showed 10 ng mL−1 as the quantitation limit and a lower extraction efficiency (37%) using LLE because the presence of glipizide did not provide a good linearity, while the application of SPE reported by Zendelovska et al. [17] also showed 10 ng mL−1 as the quantitation limit but it used expensive RP cartridge and 2.5 mL of the blood sample. Thus, the method reported by Gao et al. [24] was relatively better for studying bioavailability and bioequivalence in human beings.

Considering the high value of ratio of blood to plasma (6:1), Jain et al. [25] in Mar 2006 considered advantageous to estimate a low dose Indp in whole blood from 1.5 mg controlled-release tablets; RBCs were ruptured at −70 °C and using a hypertonic solution of zinc sulphate further haemolysis of RBC was done to precipitate out; LLE was carried out with EtOAc along with glimepiride (a sulfonylurea) as internal standard. The overall mean recovery for Indp was >81%. The sample containing both Indp and the internal standard was analysed in total run time of 2.5 min with MeCN-ammonium acetate buffer of 10 mM and pH 3.5 (90:10, v/v) by RPLC using LC-MS-MS (C18 column) for ionization of Indp and glimepiride and the analysis was performed via MRM acquisition and quantitation limit of 0.5 ng mL−1 was achieved for Indp. The advantages of the method include (i) higher selectivity, (ii) no need to separate Indp and internal standard, and (iii) it required only 0.5 mL of blood [25].

In the same year, in Jun 2006, Ding et al. [26] extracted Indp and glibenclamide (a second-generation sulfonylurea antidiabetic agent, as the internal standard) from human plasma by LLE using EtOAc with a recovery of 90.5–93.9%. Indp was separated with MeOH-ammonium acetate buffer of 10 mM (78:22, v/v) by RPLC using LC-MS-MS (C18 column). LC–ESI-MS was performed in the selected ion monitoring (SIM) mode in a single quadrupole mass spectrometer. The LOQ was 0.1 ng mL−1, as against the previous report of 01ng mL−1 [23]. Though, the method reported by Jain et al. [25] was claimed to be useful to monitor the total pre-clinical and clinical pharmacokinetic ADE (absorption, distribution and elimination) profile of single or multiple dose. Since the concentration of Indp in human plasma is much lower than that in human whole blood and the methods reported earlier [24–26] for bioassay of Indp provided LLOQ of the order of 5–50 ng mL−1 the method described by Ding et al. [26] showed successfully a very low quantitation limit of 0.1 ng mL−1 in plasma of male healthy Chinese volunteers.

In an approach to study the Pharmacokinetic (PK) and bioequivalence of Indp tablets in the drug-free human plasma (obtained from healthy male volunteers of Ibni-Sina hospital, Ankara, Turkey) within a 96 h period, Ateş et al. [27] extracted Indp and sulfamethazine (internal standard) by LLE with Et2O from plasma. UPLC system equipped with Tunable UV (TUV) detector and C18 column (L × i.d., 100 × 2.1, 1.7 μm) using MeCN-phosphate buffer flowing at 0.5 mL min−1 with gradient composition in 07 min was successful for separation and detection in UV at 241 nm. The phosphate buffer was brought to pH 3.33 by adding 85% o-phosphoric acid. The pH of extraction medium was brought to pH 6.66 by the addition of phosphate buffer which enhanced the drugs' dissociation from the plasma. The method did not offer any improvement over any of the previously reported methods, e.g. [27]. However, the TUV detector is considered to have better sensitivity than PDA detector. Optimal resolution and sensitivity for UPLC was provided by the use of TUV detector because it has a larger slit width (≤5 nm) and allows more light into the flow cell in comparison to the fixed slit width of PDA detector to establish 1.2 nm resolutions across the diodes.

Indp concentrations in plasma were assayed by LC-ESI-MS method [28] in the samples of plasma obtained from 20 healthy Chinese male volunteers with 2-way crossover study in random, open single-blind manner. Prednisone was used as the internal standard and LLE was adopted for extraction of both Indp and the internal standard. Zorbax Eclipse XDB-phenyl column and MeOH-ammonium acetate buffer of 10 mM and pH 5.0 (50:50, v/v) were used for separation and analysis supplemented with a single quadrupole mass spectrometer that took overall 13 min. The MS was applied in negative ion and SIM mode. The method of HPLC-MS/MS reported by Jain et al. [25] was much more sensitive and reliable though they adopted a superior and more expensive instrument.

Nakov et al. in 2013 [29] used automated SPE for sample extraction of Indp from human whole blood. Kinetex C18 core shell column and MeCN-2 mM ammonium formate (90:10, v/v) were used for separation in conjunction with MS in a total time of 2.5 min. The application of MS using positive electrospray ionization in MRM mode was able to characterize both Indp and the internal standard (i.e., zolpidem tartarate, an imidazo [1,2-a]pyridine compound). SPE provided recovery >90% for Indp from the whole blood (using 0.5 mL only) and thus the method was applicable for studies related to bioavailability and pharmacokinetic of Indp.

In 2013, Ramkumar et al. [30] determined Indp urine samples of humans considering it as the maladaptive drug. Undecan-1-ol was used for extraction of Indp as the low-density solvent which is immiscible with water, has a density (0.83 g mL−1) lower than water, and high extraction capability for Indp. It has lower toxicity in comparison to chlorobenzene or other chlorinated solvents that were used earlier [31]. They developed microextraction method (and used only a few microliters of the solvent) based on emulsification caused by ultrasound. It was termed as ‘low-density solvent (LDS) based ultrasound assisted emulsification microextraction (USAEME) method’. Separation was successful using a C18 HTec column with HPLC-variable wavelength detection (HPLC-VWD) system and MeCN-phosphate buffer (60:40, v/v) flowing at 01 mL min−1. The phosphate buffer was brought to pH 3 by adding o-phosphoric acid. Detecting at 240 nm in the UV range, the LOD was 0.3 ng mL−1 [30]. Figure 2 shows chromatogram of Indp using LDS based USAEME method combined with HPLC-VWD. Undecan-1-ol was used as extraction solvent (with ultrasonication for 2 min) and the emulsion so formed was centrifuged. The supernatant was used for HPLC-VWD analysis after (1:1) dilution with the MP. With the decrease in the size of the droplet of the solvent and with the usage of ultrasound energy the contact surface between the extracting solvent and the other immiscible liquid present in the system is enhanced, it results into easy mass-transfer of Indp and hence effective extraction with a very low amount of organic solvent compared to LLE and SPE [30]. Thus, the combined application of the said extraction method with HPLC-VWD was free from effects of matrix and required less time for analysis.

Fig. 2.
Fig. 2.

Chromatogram of Indp in urine sample, spiked with 50 ng mL−1 of target analyte, using ‘LDS based USAEME’ method combined with HPLC-VWD, adapted from [30]

Citation: Acta Chromatographica 36, 2; 10.1556/1326.2023.01123

Assay of Indp in whole blood was made by Pinto et al. [32], in 2014.Two controlled release forms of Indp (containing1.5 mg) were fed to fifty-two volunteers of healthy Brazilians. Indapamide-d3, as the internal standard, was first added to whole blood and, after vortex mixing, extraction was carried out with Et2O followed by experimental work up involving centrifugation, and evaporation to dryness. LLE provided a recovery of nearly 83%. The sample was finally reconstituted in a mixture of 7.5 mM aq ammonium acetate and MeOH (30:70); it was loaded onto Synergi Polar RP-column for separation using 5 mM aq ammonium acetate (containing 1mM HCOOH)-MeOH (40:60, v/v) for a 3.0 min run. Detection was made by MS with electrospray ion source in a mode of negative ionization with the lowest limit of 0.25 ng mL−1. Deuterated internal standard did not cause interference in the detection process since its characteristics were similar to Indp. Previous reports on the assay of Indp in biological fluid samples [12, 16, 23, 28, 33, 34] required 8–15 min as the time for chromatographic run, and the quantitation was of the order of 2 [12] and 10 ng mL−1 [35]. Thus, the method reported by Pinto et al. [32] can be considered an improvement with advantages in comparison to the previous reports, as cited herein.

In 2018, Hang and associates [36] described assay of Indp and perindopril simultaneously after the European Hypertension Guidelines [37] suggested an update for combination of these two APIs as one of priority combinations of antihypertensive drugs. They reported a comparative pharmacokinetic study for the two in whole blood and plasma obtained from ten volunteers of good health in China. Method of extraction was appropriate for both plasma and whole blood. Protein precipitation by MeCN or 14% perchloric acid provided the best recovery for Indp and perindopril, respectively, as pre-treatment of the bio samples. The protein precipitation method was simpler and faster for high-throughput analysis, in comparison to LLE and SPE methods. Hyphenated UPLC-MS-MS was used with Hypersil C18 column. Quantitation was done with positive electrospray ionization and MRM mode. Since Indp and perindopril have different physiological properties the conditions for chromatographic separation worked out were different. MP consisting of mixtures of 0.05% ammonium acetate and 0.2% formic acid with MeOH-H2O or only MeOH were used in linear gradient elution at 0.65 mL min−1. Since Indp is known to have high binding to the red blood cells its concentration was found to be higher in whole blood than that in plasma in terms of Cmax and AUC0–t values. Method [36] does not present any novelty over the existing methods and has neither been suggested nor used for drug abuse studies. Moreover, application of perchloric acid during sample preparation is not considered a good approach and authors have not suggested/worked removing it. Hang et al. [12] had earlier used HPLC-UV approach for determination of only Indp from human blood only.

It was observed that (i) there was poor recovery of Indp from plasma samples so it could be quantified only in blood samples in high concentrations [25, 32, 36] and not in plasma, and (ii) the new formulation containing three APIs (namely, amlodipine, Indp and perindopril) was being used for treatment of high blood pressure due to arterial hypertension [38]. Considering this literature, Rezk and Badr in 2020 [39] described quantitation of Indp in plasma collected from six batches of 26 Egyptian individual adult volunteers. Methyl t-butyl ether-dichloromethane-ethyl acetate (40:40:20, v/v) was used to extract the APIs by LLE approach in one step (with a recovery of >91%). As per earlier reports [32], Indp-d3 was the internal standard. Quantitation was done with positive EIS modeusing UPLC-MS-MS. C18 column (L × i.d., 100 × 2.1 mm, 1.7 μm) and 10 mM ammonium acetate (containing 0.2% formic acid)-MeOH (60:40, v/v) flowing at 0.3 mL min−1, in isocratic mode, were used for separation. The LOQ was 0.5 ng mL−1. Method was successful for bioequivalence, pharmacokinetic and clinical investigations of three APIs together.

LLE (for extraction of Indp from different types of biological fluids) followed by LC-MS/MS [25] or HPLC/UV method [9, 12, 18] has been used by several workers. LLE is cumbersome and unsatisfactory (in comparison to SPE approach) because it (i) involved endogenous interferences due to multiple steps of extraction, (ii) provided poor recovery of Indp, (iii) required nearly 1 h, and different pH values to extract basic, acidic and neutral analytes, and (iv) evaporation of the extracted solvent to obtain matrix or impurity free extracts and to increase recovery. A summary of different methods used for estimation of Indp with respective columns, MP and LOD have been compiled in Table 1.

Table 1.

Summary of different methods used for estimation of Indp

MethodColumnMobile PhaseLOD/LOQReference
HPLCC18 column (L × i.d., 250 × 4.6 mm, having dimethyl-octadecylsilanegroups to Zorbax 5 μm silica particle for plasma and LiChrosorb C18 column for blood and urineacetonitrile -0.1 M sodium acetate pH 3.6 (43:57, v/v) for plasma; acetonitrile-0.1 M sodium acetate pH 3.6 (36:65, v/v) for blood and urine50 ng mL−1 for blood and urine, and 25 ng mL−1 for plasma (LOD)[8]
HPLCC18 column80 mM ammonium acetate, pH 3.5 (adjusted with conc HCl)- acetonitrile-2-propanol (65:30:5, v/v)10.0 ng mL−1 (LOQ)[9]
HPLCUltrasphere ODS column, L × i.d., 75 × 4.6-mm, 3 μmacetonitrile–water (45:55, v/v) containing 5 mM KH2PO4–K2HPO4 (pH 4.0)01 ng mL−1 (LOD)[10]
HPLCC18acetonitrile-water (pH 2.8) (35:65, v/v)25  ng L−1 (LOD)[11]
HPLCInertsil ODS-3 analytical columnphosphate buffer (a solution of 2 g of KH2PO4, 3 mL of H2SO4, and 3.5 mL of TEA in 1 L of water)–acetonitrile (aq 40%)–methanol (55:45:5, v/v) in isocratic mode10 ng mL−1 (LOQ)[12]
GC–MSphenyl-methylsilicone columnCarrier gas He40 μg L−1 (LOD)[16]
HPLCC8 columnTEA in water (0.1%, v/v, pH 3.5 adjusted with conc-phosphoric acid)-acetonitrile (63:37, v/v)4.0 ng mL−1 for human serum & 20.0 ng mL−1 for blood samples (LOD)[17]
LC/MS/MSNucleosil C18 column1% acetic acid and acetonitrile50 ng mL−1 (LOD)[18]
HPLC and ESI tandem MSC18 guard columnSolvent A (2% aq formic acid), solvent B (water), and solvent C (acetonitrile)–constant 10% A throughout the run, 0% C (0–1 min), 0–80% C (1–6.5 min), 80% C (6.5–7.5 min), 80-0% C (7.5–8 min), and 0% C (8–11 min)100 ng mL−1 (LOD)[22]
HPLC, AP-ESI)C18methanol-aq. 0.1% formic acid (42.5:57.5, v/v)1 ng mL−1 (LOD)[23]
HPLCC18acetonitrile–propan-2-ol–0.1 TEA in water (adjusted to pH 3.75 with 85% phosphoric acid) (35:5:60, v/v) and UV detection at 240 nm5.0 ng mL−1 (LOQ)[24]
RPLCC1810 mM Ammonium acetate pH 3.5)-acetonitrile (10:90, v/v)0.5 ng mL−1 (LOQ)[25]
LC-ESI-MSC1810 mM ammonium acetate–methanol (22:78, v/v)0.1 ng mL−1 (LOQ)[26]
UPLCC18acetonitrile-sodium dihydrogenphosphate buffer (adjusted to pH 3.33 with 85% o-phosphoric acid)1 ng mL−1 (LOQ)[27]
LC-ESI-MSZorbaxEclipse XDB-phenyl columnammonium acetate buffer (10 mM, pH 5.0)–methanol (50:50, v/v)0.2 ng ml−1 (LOD)[28]
SPE-LC-MS/MSKinetex C18 core shell columnacetonitrile and 2 mM ammonium formate (90:10, v/v)1 ng mL−1 (LOQ)[29]
HPLC-variable wavelength detectionC18H Tec columnphosphate buffer (adjusted to pH 3 with o-phosphoric acid)–acetonitrile (40:60, v/v)0.3 ngmL−1 (LOD)[30]
LC-MS/MSSynergi Polar RP-columnmethanol-5mM aq ammonium acetate containing 1 mM formic acid (60:40, v/v)0.5 ng L−1 (LOD)[32]
UPLC–MS/MSC18methanol-10 mM ammonium acetate with 0.2% formic acid (60:40, v/v)0.5 ng L−1 (LOD)[39]

Nevertheless, there remains a prime concern to have a single analytical method with the capability of efficient extraction procedure and throughput with good sensitivity to investigate the pharmacokinetic in terms of ADE. GC-MS or LC-MS-MS, allowing high selectivity and high-resolution remain among the preferred approaches. High speed GC (generally with hydrogen as carrier gas) and UHPLC minimise the analysis time. Certain impurities or the undesirable components going into the extract from the matrix (i) may not be observed in chromatograms, (ii) may cause ion suppression, and thus adversely affect the overall analysis [40].

4 Enantioseparation of Indp

Literature search on the enantioseparation studies of Indp showed that most of the papers published in this area focused on the evaluation of the performance of available CSPs rather than individually focusing on enantioseparation of Indp. There are just a few reports on the pharmacokinetics and pharmacological properties of individual enantiomers of Indp. The methods available so far, for enantioseparation are scare and, therefore, it is all the more important to study and evaluate the available methods of enantioseparation of Indp so a review presentation of these methods will help the scientists find suitable methods for separating the enantiomers.

Bataillard et al. [6] presented a summary of certain experiments, performed on animals, that demonstrated the pharmacological effects of Indp related to antihypertensive action, diuretic effects, effects on calcium channels, and interaction with endothelial factors; it covered thirty-three references published during 1975–1978. In 2018, Patil et al. [4] summarised application of certain analytical methods for assay of Indp in biological fluids, and formulations of APIs in the market or in bulk covering 56 references for the period 1995 to 2014 largely drawn from less known journals and without commenting on the merits/limitations. These two papers and the references cited therein did not address PK and Pharmacodynamics differences of the two enantiomers. It is evident from the discussion and the references cited in the previous section of this paper focused on bioassay, bioequivalence and drug screening studies of Indp in biological fluids that no concluding studies could be noted that could show or establish the different physiological or pharmacological behaviour of Indp enantiomers [41, 42] and there was no attention to the selective behaviour and separation of the two enantiomers of Indp.

Enantioseparation using CSPs or chiral derivatizing reagents (CDRs) are termed as direct and indirect approaches, respectively. There are known advantages and limitations of both the approaches. The application of CDRs in the indirect approach provides its structural characteristics to the pair of diastereomeric derivatives so synthesized which are helpful in spectrophotometric detection on achiral columns in economical manner as compared to the CSPs used for direct approach (generally using HPLC, CEC, and SFC). The chemical nature of the commercial CSPs including particle size, column length etc along with application protocols are mostly described by the manufacturers/suppliers of such CSPs.

4.1 HPLC enantioseparation of Indp

4.1.1 Polysaccharide based CSPs

The fundamentals of mechanistic aspects of separation on polysaccharide based CSPs, having phenylcarbamate moieties were described much earlier [43, 44] and the same holds good at present too. The Chiralcel OD-R column could be operated using 100% MeCN or 100% MeOH and 20–100% water in the pH range of 2–7 for maximum column life as per the manufacturer (Chiral Technologies, Inc., Exton, PA, USA). It allowed the use of aq organic modified MPs (without the use of buffers). It was successful for RP-HPLC enantioseparation of Indp (and a few other pharmaceuticals) using water-MeCN (60:40, v/v) in isocratic mode flowing at 0.5 mL min−1 and detection at 210 nm with directly coupled ESI-MS [45]. The method was useful as MP used was readily compatible with the ESI without the need for post-column addition of an organic solvent which otherwise is generally required to overcome the miscibility problem and to improve the electrospray ionization process. Though the retention times of the two enantiomers were 24.57 and 37.20 min with Rs = 7.51 the method was not able to provide elution order of the enantiomers and thus unable to recognize the enantiospecificity.

The stereospecific, NP HPLC method for the separation of enantiomers of Indp in whole blood along with its pharmacokinetics study in rats up to 24 h after single oral dosing was one of the earliest methods in this direction [46], taking into account references [41, 42]. Whole blood of rat was selected considering preferential binding of Indp to red blood cells. Using Chiralpak IC analytical column containing cellulose tris (3,5-dichlorophenylcarbamate) with isopropanol-hexane (30:70, v/v) as the MP and UV detection at 240 nm Indp enantiomers were well resolved with Rs = 2.0 and the LOQ was 0.05 μg mL−1 for each isomer. The elution order was determined by using an automatic polarimeter. The retention times of (+)-, (−)-Indp and internal standard (hydrocortisone acetate) were 19.2, 23.3 and 12.9 min, respectively. The mean extraction efficiency was >86% for each enantiomer. An oral administration of 12 mg kg−1 of racemic Indp to the rats, showed that enantiomers were very fast absorbed from tablets resulting in maximum concentration (Cmax) 20.11 ± 3.47 g mL−1 and 20.50 ± 3.48 g mL−1 for (+)- and (−)-Indp, respectively, and these were obtained at almost same time for both the enantiomers, viz, Tmax (0.70 ± 0.07 h for (+)-isomer and 0.69 ± 0.04 h for (−)-isomer. The two pharmacokinetic parameters Cmax and Tmax were not significantly different between the two enantiomers. The concentration of (−)-Indp in blood was slightly higher than (+)-Indp at the first five points, and then it was a little lower than that of (+)-Indp during drug elimination in every rat. The elimination half-life was in the range 4.9–5.5 h for (−)-isomer and 4.8–5.3 h for (+)-isomer; it could be explained by the fact that Indp enantiomers undergo a very limited (+)- to (−)-inversion. Differences between pharmacokinetic parameters of the two enantiomers were evaluated by samples paired T-test using IBM SPSS Statistics 19 (SPSS, Inc., Chicago, IL, USA). Since the differences between the pharmacokinetic parameters t1/2, AUC0−24, AUC0−∞ and CL/F (i.e., the ratio of apparent clearance to bioavailability) were significant (P < 0.05), the disposition of the two enantiomers was concluded to be different. However, further investigation is still needed. Figure 3 shows typical chromatograms of whole blood samples obtained at 10 min after a single dose rac-Indp [46].

Fig. 3.
Fig. 3.

Typical chromatograms on a cellulose tris(3,5-dichlorophenylcarbamate) column (Chiralpak IC) of whole blood sample obtained at 10 min after an oral administration of 12 mg kg−1 of rac-Indp to the rats; the retention times of 1, (+)-Indp, and 2, (−)-Indp were 19.2, 23.3 min, respectively, and 12.9 min for internal standard (hydrocortisone acetate), adapted from [46]

Citation: Acta Chromatographica 36, 2; 10.1556/1326.2023.01123

4.1.2 Whelk-O 1 CSP

The Whelk-O 1 CSP is available under the categories of Pirkle-type, chiral HPLC and SFC columns. The broad versatility observed on the Whelk-O 1 column compares favourably with polysaccharide-derived CSP. These columns are designed in such a way that diffusion only occurs in the porous, outer layer of the particle, rather than the entire particle providing faster and efficient separations. The CSP was originally developed in 1992 for enantioseparation of naproxen [47, 48]. Indp was found to be optimally resolved with MP consisting of IPA: hexane (1:1, v/v) flowing at 1.0 mL min−1 with UV detection at 254 nm [49]. The chromatographic data is shown in Table 1 [49]. The polar sulphonamide moiety causes strong retention and makes the resolution difficult, it was overcome by using a higher concentration of IPA or using a ternary MP by adding dichloromethane or MeCN to hexane-IPA.

4.1.3 Protein based CSPs (Ovomucoid or α1-acid glycoprotein (AGP))

An ovomucoid protein-based column was successful [50] for enantioseparation of racemic Indp under isocratic MP composition of phosphate buffer (Na2HPO4, 10 mM, pH 3.1 adjusted with MeCN and a solution of 10% o-phosphoric acid (10:90, v/v) at 1 mL min−1 and detection at 242 nm. The results showed good separation (tR1 and tR2 5.50 and 7.09, respectively, Rs = 3.83; α = 1.28). Using the same ovomucoid protein-based column, the same group of workers, reported simultaneous enantioseparation of perindropil tert-butylamine (Ptba, an ACE inhibitor) and Indp (in the combination drug used as racemic mixtures in therapy) with the MP consisting of (Na2HPO4, 20 mM, pH 3.75 adjusted with a solution of 10% o-H3PO4) and MeCN (93:7, v/v) at 1 mL min−1 under an isocratic elution [50], in less than 15 min. Optimal pH could not be established for a simultaneous enantioseparation because of the different pKa values of the two analytes and pI of the ovomucoid. The Rs values were 2.32 and 1.76 for Ptba and Indp, respectively. However, the authors could neither differentiate the peaks for the two enantiomers nor establish the elution order, in both the papers.

4.1.4 β-CD CSPs

CD bonded stationary phases first commercialized as RP CSPs for LC were subsequently, used for direct enantioseparation in CE, GC, and SFC [51]. In 1990, Armstrong et al. [52] synthesized several different derivatized b-CDs with acetic anhydride, (R)- and (S)-1-(1-naphthyl)ethyl isocyanate, etc. and used them as CSPs in normal-phase LC. The enantiomeric separation mechanism on these phases was not thought to be dependent on inclusion complexation in contrast to chiral separations on the native CD stationary phase. These CSPs resembled closely the functionalized cellulosic stationary phases (developed by Okamoto et al. in Japan) [53, 54] than the original native CD bonded-phase packings. Armstrong et al. developed naphhylethylcarbamate (NEC)-functionalized β-CD stationary phase [55]. The configuration of (R)- or (S)-NEC-β-CD bonded phases and the pH were found to play an important role in the enantiomeric separation process in RP-mode (which could provide π-π stacking sites in contrast to the inclusion complex formation mechanism of native β-CD CSPs). Enantioseparation of Indp was achieved using MeCN-1% triethylammonium acetate buffer (20:80, v/v) at a flow-rate of 1.0 mL min−1, pH 4.5 was successful for both (R)-, and (S)-configurations while the configuration (S)- also provided enantioseparation at pH 7.1, the values of (α) were 1.04 and 1.15 at pH 4.5 while (α) was 1.18 at pH 7.1 in RP-HPLC.

In 2006, Zhong et al. [56] reported the first synthesis of dinitrophenyl (DNP) substituted β-CD derivatives (with π-acidic moieties). The bonded sorbents were prepared through carbamate linkage or ether linkage and the degree of substitution of the DNP group on β-CD was in the range from 3 to 5. The CSPs bonded through ether linkage were successful in enantioseparation of Indp with Rs = 2.90 when there was an additional trifluoromethyl group on the phenyl ring of CSP (that made the CSPs even more π-electron deficient) using TEAA buffer (composed of 0.1% (v/v) TEAA in water, pH 4.1)-MeCN-water (0.1:15:85, v/v), while the Rs was 1.10 when the CSP had randomly arranged DNP groups on the CD rims and TEAA buffer-MeCN-water (0.1:25:75, v/v) [56]. The CSPs were slurry packed into stainless steel columns and more than 200 racemic aromatics were subjected to enantioseparation using reversed-, polar organic-, and normal modes of MP while we have taken data for Indp.

Two covalently bonded cationic β-CD CSPs were prepared by graft polymerization of “6A-(3-vinylimidazolium)-6-deoxyperphenylcarbamate-β-cyclodextrin chloride” (VIMPCCD) or “6A-(N,N-allylmethylammonium)-6-deoxyperphenylcarbamoyl-β-cyclodextrin chloride” (VAMPCCD) onto silica gel. VIMPCCD and VAMPCCD were chemically bonded onto vinylized silica gel through co-polymerization with 2,3-dimethylbutadiene (DMBD) under the free radical initiation by 2,2′-azo-bis-isobutyronitrile (AIBN); the CSPs were designated as IMPC and AMPC, respectively. These were successfully applied for HPLC enantioseparation of Indp along with a few more racemic pharmaceuticals [57]. Enantioseparation of Indp using NP-HPLC on IMPC with IPA-n-hexane (30:70, v/v) showed Rs = 1.10 while Rs was 0.87 using AMPC. The results showed that the cationic imidazolium-containing β-CD CSP (IMPC) afforded better enantioseparation than that containing ammonium moiety under NP-HPLC; stronger Hydrogen bonding with analytes in NP-HPLC enhances the retention and enantioseparation of HPLC.

4.1.5 Crown ethers

Crown ethers form host-guest complexes with a variety of organic compounds and metal ions [57–59]. Berkecz et al. [60] reviewed role of CSPs based on crown ethers in LC enantioseparation. Thamarai Chelvi et al. [61] in 2014, reported synthesis of 4-isopropylcalix[4]arene-capped “(3-(2-O-β-cyclodextrin)-2-hydroxypropoxy)propylsilyl” appended silica particles (IPC4CD-HPS). The synthetic IPC4CD-HPS particles were packed into a stainless-steel column (L × i.d., 150 × 2.1 mm), and was used for HPLC enantioseparation of certain chiral drug compounds. Indp was enantioseparated using CH3OH-water (20:80, v/v) as the MP and the values of Rs and (α) were 6.54 and 3.57, respectively. The cooperative functioning of the two anchored functional moieties, and multiple interactions with the components of the analyte enhanced chiral recognition and provided base line separation of the two enantiomers. The native calix[4]arene-capped β-CD-bonded phase C4CD-HPS [62] provided Rs 5.14 and (α) 3.14, respectively, using MeCN-water (60:40, v/v) as the MP for enantioseparation of Indp which were lower than those obtained by using the CSP, IPC4CD-HPS [62]; Fig. 4a shows typical chromatogram for enantioseparation of Indp on C4CD-HPS-packed column.

Fig. 4.
Fig. 4.

a) Enantioseparation of Indp on C4CD-HPS-packed column, MP: MeCN-water (60:40, v/v), adapted from [62]; b) Enantioseparation of Indp on column packed with crown ether (BAMCR-HPS), MP: MeOH-water (10:90, v/v), detection at 254 nm UV, adapted from [64]

Citation: Acta Chromatographica 36, 2; 10.1556/1326.2023.01123

Ma et al. [63] in 2017 reported the synthesis of crown-ether-based CSP, i.e., “aza-15-crown-5-capped (3-(C-methylcalix[4]resorcinarene)-2-hydroxypropoxy)-propylsilyl” (MCR-HP)-appended silica particles (15C5-MCR-HPS). The CSP, (15C5-MCR-HPS) was packed into a stainless-steel column which was used for HPLC enantioseparation of Indp using water-MeCN (90:10, v/v) in NP mode at a flowing at 0.2 mL min−1. The values for Rs and (α) were 2.30 and 1.83, respectively. Earlier, Tan et al. [64] prepared “methylcalix[4]” bonded stationary phases, “(3-(Cmethylcalix[4]resorcinarene)-2-hydroxypropoxy)-propylsilyl”-appended silica particles (MCR-HPS) and bromoacetate-substituted MCR-HPS particles (BAMCR-HPS) shown in Fig. 5a) and the latter was used as CSP for enantioseparation of Indp (and some other racemates) on column packed with it using MeOH-water (10:90, v/v) as the MP when Rs and (α) were 2.09 and 1.45, respectively. The BAMCR-HPS phase had the limitation that it could partially resolve Indp and certain other simple racemates, as shown in a typical chromatogram for Indp (Fig. 4b).

Fig. 5.
Fig. 5.

The structures for (a) bromoacetate-substituted MCR-HPS particles (BAMCR-HPS), adapted from [64]; basic units of the CSPs (b) polyacrylamide type, prepared by radical copolymerization of N-acryloyl-l-phenylalanine ethylester with silica gel previously modified by covalent attachment of methacryloyl groups, and (c) cellulose tris(3,5-dimethylphenylcarbamate)coated on silica gel (5 μm) silanized with (3-aminopropyl)-triethoxysilane, adapted from [67]

Citation: Acta Chromatographica 36, 2; 10.1556/1326.2023.01123

The 15C5-MCR-HPS-packed column [63] exhibited better enantioseparation compared to the single-type chiral selector BAMCR-HPS-packed column [64]. The synthesis of 15C5-MCR-HPS [63] involved preparation of BAMCRHPS [64] and the latter was prepared by first anchoring C-methylcalix[4]resorcinarene (MCR) onto silica gel particles followed by treatment with bromoacetyl chloride in the presence of AlCl3 and the BAMCRHPS so prepared was reacted with excess aza-15-crown-5 in anhydrous MeCN in the presence of K2CO3 by refluxing for 24 h under the protection of dry N2 gas; it further involved several washings, Soxhlet extraction and drying for 6 h under vacuum, followed by a procedure of packing [62]. Thus, the overall procedure using different crown ether type CSPs have been highly cumbersome and time consuming. Table 2 shows, resolution of Indp enantiomers observed with different types of columns and MP.

Table 2.

Chromatographic conditions and data for enantioseparation of Indp

ColumnMobile PhaseRsReference
Chiralcel OD-Rwater-acetonitrile (60:40, v/v)7.51[45]
Chiralpak IChexane-isopropanol (70:30, v/v)2.0[46]
Whelk O1hexane-isopropyl alcohol (1:1, v/v)1.68 (α)[49]
Ovomucoidphosphate buffer (Na2HPO4, 10 mM, pH 3.1, adjusted with a solution of 10% o-phosphoric acid) and acetonitrile (90:10, v/v)3.83[50]
NEC-β-CDacetonitrile-1% TEA acetate buffer (20:80, v/v)1.04 (α)[55]
DNP-β-CDTEAA buffer (composed of 0.1% (v/v) triethylammonium acetate in water, pH 4.1)-acetonitrile-water (0.1:15:85, v/v)2.90[56]
IMPCn-hexane-isopropyl alcohol (70:30, v/v)1.10[57]
AMPC.n-hexane-isopropyl alcohol (70:30, v/v)0.87[57]
IPC4CD-HPS (crown ether)methanol-water (20:80, v/v)6.54[61]
C4CD-HPSacetonitrile-water (60:40, v/v)5.14[62]
15C5-MCR-HPSwater -acetonitrile (90:10, v/v)2.30[63]
BAMCR-HPSMeOH-H2O (10:90, v/v)2.09[64]

4.2 Capillary electrochromatography (CEC)

CEC is a hybrid technique of capillary electrophoresis (CE) and HPLC. CEC shows good separation efficiency because the MP is moved through the chromatographic bed by an electric field (electroosmosis flow, EOF) rather than by enforced pressure and it can separate both charged and uncharged compounds; capillaries in EC, packed with HPLC stationary phase are subjected to a high voltage and separation is achieved by differential partitioning between the liquid and solid phases when the electrophoretic migration of solutes occurs [65, 66]. CE in comparison to HPLC, shows narrower peaks and better resolution. Also, CE has a greater peak capacity in comparison to HPLC in analytical chemistry for chiral separations. CE has the advantages of use small amounts of sample, chiral selector as well as the solvents. Chiral separartions of uncharged compounds, unlike in HPLC cannot be done through CEC. However, CEC was used for enantioseparation of Indp as an alternative to HPLC methods. The following section describes enantioseparation of Indp using different chiral selectors.

4.2.1 Cyclodextrin (CD)

Keeping in view the capability of derivatized CDs in enenatioseparation, Vescan et al. [5] used CE for enantioseparation of Indp. Sulfobuthyl ether-β-CD (anionic substituted derivative), was found to be successful using a buffer solution of 25 mM Na2HPO4–25 mM NaH2PO4 (pH 7) and 5 mM sulfobuthyl ether-β-CD as chiral selector (added to the background electrolyte) at voltage of +25 kV, temperature 15 °C and diode array UV detection at 242 nm in 6 min, with Rs of 4.30 and a separation factor (α) of 1.08. Separations were performed on uncoated fused silica-capillaries (L × i.d., 48 cm × 50 μm). The method was recommended for laboratories performing routine analysis of Indp. The authors didn't have pure enantiomers of Indpto establish the migration order, therefore, the migration order was reported as enantiomer 1 and enantiomer 2. Other CDs or their derivatives such as native neutral CDs (α-, β-, γ-CD), hydroxypropyl-β-CD, and randomly methylated β-CD were not successful under the varying conditions of pH and buffer types. Separation conditions and results of enantioseparation of Indp by CE reported by various workers are summarised in Table 3.

Table 3.

Data obtained for enantioseparation of Indp using CEC

Chiral selectorRsSeparation factor (α)BufferRef
SBE-β-CD4.301.0825 mM Na2HPO4–NaH2PO4, pH 7[5]
cellulose tris(3,5-dimethylphenylcarbamate)1.741.380.5 M NaClO4-acetonitrile (60:40, v/v)[67]
cellulose tris(3,5-dimethylphenylcarbamatewith 5 or 7 μm particle size2.66 (CEC) 1.17 (nano-LC)1.33(CEC)

1.35 (nano-LC)
phosphate buffer (5 mM, pH 7)–acetonitrile (1:1)[70]
OD type (5 μm).-1.3310 mM Na2HPO4-acetonitrile (30:70, v/v)[71]
OD type (3 μm).2.641.4110 mM phosphate buffer (pH 8.2)[72]
Chiralel OD1.592.1310 mM Ammonium acetate in methanol (pH* 7.7 (without acetic acid)).[73]

4.2.2 Polysaccharide derivatives

In 1999, fused-silica capillaries (100 μm, i.d.) modified by covalent attachment of (a) poly-N-acryloyl-L-phenylalanine ethyl ester (Chiraspher®) or (b) by coating with cellulose tris(3,5-dimethylphenylcarbamate) were used for enantioseparation of Indp [67]; the structures for basic units of the two CSPs are shown in Fig. 5b and 5c, respectively. Different separation modes were applied using essentially the same experimental set-up. Enantioseparation of Indp was successful in RP nano-HPLC using capillary columns packed (in house) with (b) type CSP and 0.5 M NaClO4-MeCN (60:40, v/v) as the MP, showing Rs = 1.74 & (α) = 1.39; the enantioseparation of Indp was enhanced by application of a voltage of 10–15 kV and pressure of 44 bar within shorter analysis time than HPLC. RP-nano-HPLC enantioseparation was performed in the same capillaries that were used for NP mode. However, nano-HPLC separations in the NP mode gave relatively high peak efficiency compared to HPLC in regular size columns while no significant gain in separation efficiency could be obtained by changing from pressure-driven to electrically-driven migration of the analytes.

Based on the information [68, 69] that cellulose derivatives could be coated onto silica gel for chiral recognition power in analytical and preparative HPLC, Mayer et al., in 2000 [70], immobilized cellulose tris(3,5-dimethylphenylcarbamate) on microporous silica gel (with 5 or 7 μm particle size and 0.4 μm pore size) and Indp was used as a test racemate to compare the performance of this CSP in the packed CEC (capillaries, L × i.d., 27/19 cm × 100 μm) and nano-LC modes. MP consisting of phosphate buffer (5 mM, pH 7)–MeCN (1:1) was used in both modes with detection at 230 nm; in nano-LC the flow-rate was below 1 mL/min under isocratic conditions and in CEC 20 kV was applied. Velocity of the MPs was adjusted in order to have approximately the same values for the CEC and nano-LC modes. Chiral separation factor (α) had practically identical values in CEC and HPLC. Under the nano-LC conditions the enantiomers exhibited slightly shorter retention time, however, separation efficiency and resolution were higher in CEC, i.e., resolution (Rs) was 2.66 in CEC and 1.17 in nano-LC. Figure 6 shows enantioseparation of Indp in nano-LC modes and the packed CEC.

Fig. 6.
Fig. 6.

Comparison of performance of immobilized cellulose tris (3, 5-dimethylphenylcarbamate) packing material in the CEC and nano-LC mode on enantiomeric separation of racemic Indp. Capillary (L × i.d., 19/27 cm × 100 μm) with cellulose derivative immobilized on silica (7 μm particle size), MP: phosphate buffer (5 mM, pH 7)–MeCN (1:1), voltage: 20 kV, UV detection at 230 nm. Nano-LC: Flow-rate: 200 nL min-1. UV detection at 230 nm. Adapted from [70]

Citation: Acta Chromatographica 36, 2; 10.1556/1326.2023.01123

Krause et al. [67] showed a comparison of applicability of polyacrylamide and polysaccharide based CSPs in CEC while Otsuka et al. [71] used cellulose tris(3,5-dimethylphenylcarbamate as CSP coated on silica-gel based 5 and 3 μm particles, that were originally meant for enantioseparation by HPLC, to establish the applicability of the CSPs in CEC. Enantioseparation of Indp was achieved using a fused-silica tubing (L × i.d., 24 cm × 100 μm) as the separation capillary, packed by a pressurized method, and 10 mM Na2HPO4-MeCN (30:70, v/v) as the MPs howing (α) = 1.33; the performance of 3 μm particle material was inferior to that obtained with 5 μm particle material. The separation efficiency in the chiral CEC system using the 5 μm type packing was found to be superior to that obtained in HPLC with the same chiral packing. An year later, Kawamura et al. [72] in 2001, reported that separation efficiency of the fused-silica capillary (L × i.d., 24 cm × 100 μm) packed by a pressurized method with 3 μm particles, coated with cellulose tris(3,5-dimethylphenylcarbamate) was superior, to the one reported previously in chiral CEC system using 5 μm particles [71]. The MP was, 10 mM phosphate buffer (pH 8.2) containing 80% (v/v) MeCN and the values of Rs and (α) were 2.64 and 1.41, respectively for enantioseparation of Indp (Fig. 7a) [72].

Fig. 7.
Fig. 7.

a) Enantioseparation of racemic Indp by CEC using cellulose tris(3,5-dimethylphenylcarbamateas CSP coated on silica-gel based 3 μm particles; Sample injection, electrokinetic, 3 s at 0.2 kV, capillary 33 cm (length of the packed portion 24 cm) × 100 μm i.d., MP: 10 mM phosphate buffer (pH 8.2) containing 80% (v/v) MeCN; adapted from [72]; b) Non-aqueous CEC enantioseparation of Indp using fused-silica capillary (L × i.d., 22/32 cm × 100μm) packed with aminopropylsilanized silica gel coated with cellulose tris (dimethylphenylcarbamate) (20.0%, w/w), MP: 10 mM ammonium acetate in MeOH (pH 6.0, without acetic acid), applied voltage 10 kV, 6 bar on inlet and outlet vial, peak of thiourea as the internal standard caused no interference and appeared much before, adpated from [73]

Citation: Acta Chromatographica 36, 2; 10.1556/1326.2023.01123

Enantioseparation of Indp (and a few other chiral compounds) was investigated in non-aqueous CEC by Girod et al. [73] using three different polysaccharide derivatives as CSPs. Figure 7b shows enantioseparation of Indp using fused-silica capillary (L × i.d., 22/32 cm × 100 μm) packed with aminopropyl silanized silica gel coated with (b) type CSP (20.0% (w/w)) and 10 mM ammonium acetate in MeOH (pH 6, without acetic acid) as the MP, at an applied voltage of 10 kV [73] showing Rs = 1.59 and (α) = 2.13. Both the CSP and the analyte were neutral and most likely their effective charge did not change in the pH range 3–7.4, therefore, the capacity factors for both enantiomers remained almost constant. It was concluded that pH together with ionic strength significantly affected the selector-selectand interactions. In general, CEC in non-aqueous solvents seems to be a promising approach for analytical enantioseparation [73].

CEC offers advantages compared to HPLC in common-size columns. The investigations [67, 71, 72] could not work out the elution order and enantioselectivity, for the two enantiomers, and are thus still considered preliminary though chiral CEC stands to be a useful technique for enantioseparation. The data on enantioseparation of Indp in non-aqueous CEC in the capillaries packed with derivatized cellulose and amylose coated in different amounts on aminopropyl silanized silica gel are summarized in Table 3.

4.3 Supercritical fluid chromatography (SFC)

Polysaccharide based stationary phases are used for the majority of chiral separations in SFC, though most columns meant for HPLC applications can be used directly. SFC is considered as a technique to use columns with sub-2 μm particles since it generates much lower pressure drops. Though for achiral SFC applications columns (both for analytical and preparative scale) are available ranging from 1.7 to 5 µm particle sizes, yet no chiral columns have been commercialized with particle sizes below 2 μm, and pH is not investigated in the CO2-based MP and the polarity of CO2 has often been equated with that of hexane. We believe that HPLC still remains the choice for development processes and chiral separations in drug discovery for its ease and less cost.

The two cationic β-CD CSPs namely, VIMPCCD and VAMPCCD covalently bonded onto vinylized silica gel through under the free radical initiation by 2,2′-azobis-isobutyronitrile (AIBN), which were applied for HPLC enantioseparation of Indp along with a few more racemic pharmaceuticals [57], were designated as VIMPCCD-poly and VAMPCCD-poly by the same group of Wang et al. in the same year 2012 [74]. These CSPs were applied in SFC conditions with high contents of polar modifiers in MPs for enantioseparation of Indp and a few other racemates; these cationic β-CD derivatives contained appropriate function groups and accordingly provided more prominent enantioseparation of Indp (α = 1.19) in SFC (flowing at 1.0 mL min−1, oven temp 40 °C, 10 vol% MeOH as the modifier in CO2) in comparison to the LC column (5 μm particle size) with (R)- and (S)-naphthylethylcarbamate-β-CD CSPs with (α) = 1.04 for Indp [55, 75]. Comparison between SFC and LC showed that selectivity was sometimes lower in SFC than in LC, and the higher resolution in SFC than in LC was due to improved efficiency in SFC.

To evaluate the CSP performance in SFC and LC, a Standard Reference Material (SRM) consisting of five C2H5OH solutions, each containing one racemic or enantiomerically enriched (non-racemic) compound was developed. The five test compounds chosen were Indp, N-carbobenzyloxy-phenylalanine, ketoprofen, propranolol, and warfarin. An overview of macrocyclic glycopeptide-based chiral selectors for SFC was presented by Folprechtová and Kalíková [76]. Potential applications of this SRM included its use in comparing the column performance having similar chiral selectors and also, in quality control for column manufacturing. For testing column performance in terms of enantioselectivity in SFC and LC, eight commercial CSPs were assessed by Phinney and Sander [77]. The results showed that enantiomers of Indp were not separated on the Chirobiotic T CSP in LC, a partial separation was observed in SFC. Table 4 shows the comparison of chromatographic data obtained on different CSPs using LC and SFC.

Table 4.

Chromatographic data obtained on different CSPs using LC and SFC

LCSFC
CSPMobile phasek(α)RsMobile phasek(α)Rs
Chiralcel ODHexane-ethanol (50:50, v/v)1.151.883.66CO2-methanol (70:30) with 0.5% IPA3.161.355.55
Chiralpak ADHexane-ethanol (50:50, v/v)0.641.150.44CO2-methanol (85:15) with 0.5% IPA12.141.0000
Chirex 3,005Hexane-1,2-dichloroethane-ethanol-TFA (60:35:5, v/v)8.661.0000CO2:methanol (85:15) with 0.5% IPA14.151.0000
Chirex 3,022Hexane-1,2-dichloroethane-ethanol-TFA (60:35:5, v/v)9.171.101.15CO2-methanol (80:20) with 0.5% IPA11.561.051.40
ChirobioticT1% tri-ethylammonium acetate, pH 4.1-methanol (80:20, v/v)3.381.0000CO2-methanol (85:15) with 0.5% IPA19.161.031.08
ChirobioticV1% tri-ethylammonium acetate, pH 7.0-acetonitrile (90:10, v/v)2.581.050.21CO2-methanol (85:15) with 0.5% IPA22.591.041.12
CyclobondI 20001% tri-ethylammonium acetate, pH 4.1-acetonitrile(90:10, v/v)0.761.0000CO2-methanol (85:15) with 0.5% IPA9.311.0000
CyclobondI 2000 RSP1% tri-ethylammonium acetate, pH 4.1-acetonitrile(90:10, v/v)5.431.0000CO2-methanol (85:15) with 0.5% IPA18.081.0000

k’, retention factor; α, separation factor; Rs, Resolution.

Table 4 shows that higher resolution was observed in SFC using Chiralcel OD, Chirex 3,022, Chirobiotic T and Chirobiotic V. However, no resolution was observed in case of Chiralpak AD using SFC, whereas Rs = 0.44 was observed with LC. Chirex 3,005, Cyclobond I 2000 RSP and Cyclobond I 2000 could not resolve the Indp enantiomers by either LC or SFC. The data in Table 4 can be used as a guide for the selection of CSP. It was observed that the polar additive concentration affects the results in SFC. These effects were studied on CSPs having either derivatized polysaccharide or a macrocyclic glycopeptide as the chiral selector. To monitor the effects on retention, selectivity, and resolution, two basic additives, isopropylamine and TEA, were incorporated into the MeOH modifier at various. The presence and increasing concentration of additive had a significant effect on resolution. The macrocyclic glycopeptide stationary phase failed to elute many analytes in the absence of an additive. On the derivatized polysaccharide stationary phase the additives had little effect on retention, but there were significant improvements in peak shape and resolution [78].

5 Conclusion

The current requirement and direction for the methods for the extraction of Indp from various biological matrices is to have decreased quantities of organic solvents, along with simplification and miniaturization of the steps involved in sample-preparation, to make it fast, inexpensive and compatible with varied analytical instruments. The most appropriate analytical combination which involves expensive devices and specially trained staff, must be utilized.

β-CD-based and crown ether-based silica particles as CSPs in LC have been successful due to the cavity structure of β-CDs and crown ethers which form host-guest complex. Calixarenes based silica particles (as CSP), similar to crown ethers and β-CDs, also exhibited excellent inclusion abilities. Application of β-CDs has been associated with the low binding constants as a drawback. The crown ether-capped β-CDs exhibited relatively higher binding constants. In packed particle-CEC preparation of retaining frits is generally difficult requiring more skilled working and it may cause bubble formation and generate band-broadening, in monolithic material-CEC there are problems of reproducibility, loading capacity, and efficiency, and in open tubular-CEC load capacity, selectivity, and sensitivity are limited due to the presence of a low amount of the stationary phase (only onto the capillary wall). SFC cannot analyze polar solutes due to relatively nonpolar MP, CO2 and the supercritical fluid should be of high density, high diffusion coefficient, and low viscosity. Mass spectrometry in different modes is arguably the most popular “informative” detector for chromatographic separations. Moreover, CEC and SFC are much more expensive in running and equipment costs and are inconvenient in establishing the successful separation conditions in comparison to HPLC.

Different types of chromatographic methods (HPLC, CEC, SFC etc) discussed herein provide discernment and an option to select a method to (i) screen Indp for drug abuse, (ii) separate, isolate and quantify the enantiomers of Indp and (iii) investigate their pharmacokinetics as markedly different species and not as a “total drug”. The article evaluates the field's status with a broad base and practical approach so that the underlying principles are easily understood and applied by non-specialists too. Thus, there continues the importance and need to develop and execute methods for enantioselective drug screening and quantification along with pharmacokinetic and toxicological assays. Enantioselective chromatography is required to obtain both enantiomers with high enantiopurity for comparative pharmacological, toxicological, or biological evaluations.

List of abbreviations

APIs

Active Pharmaceutical Ingredients

AP-ESI

Atmospheric Pressure Electrospray Interface

BGE

Background Electrolyte

CE

Capillary Electrochromatography

CEC

Capillary Electrochromatography

CE

Capillary Electrophoresis

CDRs

Chiral Derivatizing Reagents

CSP

Chiral Stationary Phase

CD

Cyclodextrins

DNP

Dinitrophenyl

EOF

Electroosmosis Flow

HPLC

High Performance Liquid Chromatography

HPLC-VWD

HPLC-Variable Wavelength Detection

IPA

Isopropylyamine

LLE

Liquid-Liquid Extraction

LDS

Low Density Solvent

MWI

Microwave Irradiation

MP

Mobile phase

MRM

Multiple Reaction Monitoring

NEC

Naphhylethylcarbamate

NP

Normal Phase

Ptba

Perindopril Tert-Butylamine

PK

Pharmacokinetic

SIM

Selected Ion Monitoring

RP

Reversed Phase

SRM

Standard Reference Material

SFC

Superfluid Chromatography

TEA

Triethylamine

TUV

Tunable UV

USFDA

United States Food and Drug Administration

USAEME

Ultrasound Assisted Emulsification Micro Extraction

AIBN

2,2′-Azobis-Isobutyronitrile

VIMPCCD

6A-(3-vinylimidazolium)-6-deoxyperphenylcarbamate-cyclodextrin chloride

VAMPCCD

6A-(N,N-allylmethylammonium)-6-deoxyperphenylcarbamoylcyclodextrin chloride

Acknowledgement

The authors are thankful to the Alexander von-Humboldt Stiftung, Bonn, Germany, for the financial assistance provided as the stipendium (to R.B.).

References

  • 1.

    Chaffman, M.; Heel, R. C.; Brodgen, R. N.; Speight, T. M.; Avery, G. S. Indapamide: a review of its pharmacodynamic properties and therapeutic efficacy in hypertension. Drugs 1984, 28, 189235. https://doi.org/10.2165/00003495-198428030-00001.

    • Search Google Scholar
    • Export Citation
  • 2.

    FDA’s policy statement for the development of new stereoisomeric drugs, Chirality 1992, 4, 338340. https://doi.org/10.1002/chir.530040513.

    • Search Google Scholar
    • Export Citation
  • 3.

    EMA Investigation of chiral active substances (human) European Medicines Agency, 2018. [cited 2022 Jul 25]. Available from: https://www.ema.europa.eu/en/investigation-chiral-active-substances.

    • Search Google Scholar
    • Export Citation
  • 4.

    Patil, N. B.; Patil, K. B.; Wagh, M. N.; Patil, A. A. A review on analytical method for determination of indapamide in marketed pharmaceutical preparation. Pharma Tutor 2018, 6, 7988. https://doi.org/10.29161/PT.v6.i12.2018.79.

    • Search Google Scholar
    • Export Citation
  • 5.

    Tero-Vescan, A.; Hancu, G.; Oroian, M.; Cârje, A. Chiral separation of indapamide enantiomers by capillary electrophoresis. Adv. Pharm. Bull. 2014, 4, 267272. https://doi.org/10.5681/apb.2014.039.

    • Search Google Scholar
    • Export Citation
  • 6.

    Bataillard, A.; Schiavi, P.; Sassard, J. Pharmacological properties of indapamide: rationale for use in hypertension. Clin. Pharmacokinet. 1999, 37(Supplement 1), 712. https://doi.org/10.2165/00003088-199937001-00002.

    • Search Google Scholar
    • Export Citation
  • 7.

    Uehara, Y.; Shirahase, H.; Nagata, T.; Ishimitsu, T.; Morishita, S.; Osumi, S.; Matsuoka, H.; Sugimoto, T. Radical scavengers of indapamide in prostacyclin synthesis in rat smooth muscle cell. Hypertension 1990, 15, 216224. https://doi.org/10.1161/01.HYP.15.2.216.

    • Search Google Scholar
    • Export Citation
  • 8.

    Choi, R. L.; Rosenberg, M. E.; Grebow, P.; Huntley, T. E. High-performance liquid chromatographic analysis of indapamide (RHC 2555) in urine, plasma and blood. J. Chromatogr. 1982, 230, 181187. https://doi.org/10.1016/s0378-4347(00)81447-4.

    • Search Google Scholar
    • Export Citation
  • 9.

    Brent Miller, R.; Dadgar, D.; Lalande, M. High-performance liquid chromatographic method for the determination of indapamide in human whole blood. J. Chromatogr. 1993, 614, 293298. https://doi.org/10.1016/0378-4347(93)80321-T.

    • Search Google Scholar
    • Export Citation
  • 10.

    Legorburu, M. J.; Alonso, R. M.; Jimenez, R. M.; Ortiz, E. Quantitative determination of indapamide in pharmaceuticals and urine by high-performance liquid chromatography with amperometric detection. J. Chromatogr. Sci. 1999, 37, 283287. https://doi.org/10.1093/chromsci/37.8.283.

    • Search Google Scholar
    • Export Citation
  • 11.

    Pietta, P.; Calatroni, A.; Rava, A. High-performance liquid chromatographic assay for monitoring indapamide and its major metabolite in urine. J. Chromatogr. B. 1982, 228, 377381. https://doi.org/10.1016/S0378-4347(00)80458-2.

    • Search Google Scholar
    • Export Citation
  • 12.

    Hang, T.-J.; Zhao, W.; Liu, J.; Song, M.; Xie, Y.; Zhang, Z.; Shen, J.; Zhang, Y. A selective HPLC method for the determination of indapamide in human whole blood: application to a bioequivalence study in Chinese volunteers. J. Pharm. Biomed. Anal. 2006, 40, 202205. https://doi.org/10.1016/j.jpba.2005.06.035.

    • Search Google Scholar
    • Export Citation
  • 13.

    Ventura, R.; Segura, J. Detection of diuretic agents in doping control. J. Chromatogr. B 1996, 687, 127144. https://doi.org/10.1016/S0378-4347(96)00279-4.

    • Search Google Scholar
    • Export Citation
  • 14.

    Ja Park, S.; Pyo, H.-S.; Kim, Y.-J.; Kim, M.-S.; Park, J. Systematic analysis of diuretic doping agents by HPLC screening and GC/MS confirmation. J. Anal. Toxicol. 1990, 14, 8490. https://doi.org/10.1093/jat/14.2.84.

    • Search Google Scholar
    • Export Citation
  • 15.

    Lisi, A. M.; Kazlauskas, R.; Trout, G. J. Diuretic screening in human urine by gas chromatography-mass spectrometry: use of a macroreticular acrylic copolymer for the efficient removal of the coextracted phase-transfer reagent after derivatization by direct extractive alkylation. J. Chromatogr. B. 1992, 581, 5763. https://doi.org/10.1016/0378-4347(92)80447-X.

    • Search Google Scholar
    • Export Citation
  • 16.

    Amendola, L.; Colamonici, C.; Mazzarino, M.; Botre, F. Rapid determination of diuretics in human urine by gas chromatography–mass spectrometry following microwave assisted derivatization. Anal. Chim. Acta 2003, 475, 125136. https://doi.org/10.1016/S0003-2670(02)01223-0.

    • Search Google Scholar
    • Export Citation
  • 17.

    Zendelovska, D.; Stafilov, T.; Stefova, M. Optimization of a solid-phase extraction method for determination of indapamide in biological fluids using high-performance liquid chromatography. J. Chromatogr. B. 2003, 788, 199206. https://doi.org/10.1016/S1570-0232(02)01017-6.

    • Search Google Scholar
    • Export Citation
  • 18.

    Deventer, K.; Delbeke, F. T.; Roels, K.; Eenoo, P. V. Screening for 18 diuretics and probenecid in doping analysis by liquid chromatography–tandem mass spectrometry. Biomed. Chromatogr. 2002, 16, 529535. https://doi.org/10.1002/bmc.201.

    • Search Google Scholar
    • Export Citation
  • 19.

    Cooper, S. F.; Massé, R.; Dugal, R. Comprehensive screening procedure for diuretics in urine by high-performance liquid chromatography. J. Chromatogr. B. 1989, 489, 6588. https://doi.org/10.1016/S0378-4347(00)82884-4.

    • Search Google Scholar
    • Export Citation
  • 20.

    Tsai, F. Y.; Lui, L. F.; Chang, B. Analysis of diuretic doping agents by HPLC screening and GC-MSD confirmation. J. Pharm. Biomed. Anal. 1991, 9, 10691076. https://doi.org/10.1016/0731-7085(91)80046-C.

    • Search Google Scholar
    • Export Citation
  • 21.

    Carreras, D.; Imaz, C.; Navajas, R.; Garcia, M. A.; Rodriguez, C.; Rodriguez, A. F.; Cortes, R. Comparison of derivatization procedures for the determination of diuretics in urine by gas chromatography-mass spectrometry. J. Chromatogr. A. 1994, 683, 195202. https://doi.org/10.1016/S0021-9673(94)89116-8.

    • Search Google Scholar
    • Export Citation
  • 22.

    Goebel, C.; Trout, G.; Kazlauskas, R. Rapid screening method for diuretics in doping control using auto-mated solid phase extraction and liqud chromatography-electrospray tandem mass spectrometry. Analytica Chim. Acta 2004, 502, 6574. https://doi.org/10.1016/j.aca.2003.09.062.

    • Search Google Scholar
    • Export Citation
  • 23.

    Albu, F.; Georgita, C.; David, V.; Medvedovici, A. Liquid chromatography-electrospray tandem mass spectrometry method for determination of indapamide in serum for single/multiple dose bioequivalence studies of sustained release formulations. J. Chromatogr. B. 2005, 816, 3540. https://doi.org/10.1016/j.jchromb.2004.11.002.

    • Search Google Scholar
    • Export Citation
  • 24.

    Gao, X. L.; Chen, J.; Mei, N.; Tao, W. X.; Jiang, W. M.; Jiang, X. G. HPLC determination and pharmacokinetic study of indapamide in human whole blood. Chromatographia 2005, 61, 581585. https://doi.org/10.1365/S10337-005-0548-1.

    • Search Google Scholar
    • Export Citation
  • 25.

    Jain, D. S.; Subbaiah, G.; Sanyal, M.; Pande, U. C.; Shrivastav, P. Liquid chromatography–tandem mass spectrometry validated method for the estimation of indapamide in human whole blood. J. Chromatogr. B. 2006, 834, 149154. https://doi.org/10.1016/j.jchromb.2006.02.040.

    • Search Google Scholar
    • Export Citation
  • 26.

    Ding, L.; Yang, L.; Liu, F.; Ju, W.; Xiong, N. A sensitive LC-ESI-MS method for the determination of indapamide in human plasma: method and clinical applications. J. Pharm. Biomed. Anal. 2006, 42, 213217. https://doi.org/10.1016/j.jpba.2006.03.039.

    • Search Google Scholar
    • Export Citation
  • 27.

    Ateş, Z.; Özden, T.; Özilhan, S.; Eren, S. Improved ultra-performance LC determination of indapamide in human plasma. Chromatographia 2007, 66, 119122. https://doi.org/10.1365/s10337-007-0300-0.

    • Search Google Scholar
    • Export Citation
  • 28.

    Li, G.; Zhang, X.; Tian, Y.; Zhang, Z.; Rui, J.; Chu, X. Pharmacokinetics and bioequivalence study of two indapamide formulations after single dose administration in healthy Chinese male volunteers. Drug Res. 2013, 63, 1318. https://doi.org/10.1055/s-0032-1331181.

    • Search Google Scholar
    • Export Citation
  • 29.

    Nakov, N.; Mladenovska, K.; Labacevski, N.; Dimovski, A.; Petkovska, R.; Dimitrovska, A.; Kavrakovski, Z. Development and validation of automated SPE-LC-MS/MS method for determination of indapamide in human whole blood and its application to real study samples. Biomed. Chromatogr. 2013, 27, 15401546. https://doi.org/10.1002/bmc.2957.

    • Search Google Scholar
    • Export Citation
  • 30.

    Ramkumar, A.; Ponnusamy, V. K.; Jen-Fon, J. Rapid determination of indapamide in human urine using novel low-density solvent based ultrasound assisted emulsification microextraction coupled with high performance liquid chromatography-variable wavelength detection. Anal. Methods 2013, 5, 2572. https://doi.org/10.1039/c3ay40187a.

    • Search Google Scholar
    • Export Citation
  • 31.

    Regueiro, J.; Llompart, M.; Garcia-Jares, C.; Garcia-Monteagudo, J. C.; Cela, R. Ultrasound-assisted emulsification-microextraction of emergent contaminants and pesticides in environmental waters. J. Chromatogr. A. 2008, 1190, 2738. https://doi.org/10.1016/j.chroma.2008.02.091.

    • Search Google Scholar
    • Export Citation
  • 32.

    Pinto, G. A.; Pastre, K. I. F.; Bellorio, K. B.; deSouza Teixeira, L.; Carlo deSouza, W.; deAbreu, F. C.; Cardoso, F. F. deS. e S.; Pianetti, G. A.; César, I. C. An improved LC-MS/MS method for quantitation of indapamide in whole blood: application for a bioequivalence study. Biomed. Chromatogr. 2014, 28, 12121218. https://doi.org/10.1002/bmc.3148.

    • Search Google Scholar
    • Export Citation
  • 33.

    Chen, W.; Liang, Y.; Zhang, H.; Xiong, H. Y.; Xie, W. G. Simple, sensitive and rapid LC-MS method for the indapamide in human plasma- application to pharmacokinetic. J. Chromatogr. B. 2006, 842, 5863. https://doi.org/10.1016/j.jchromb.2006.03.024.

    • Search Google Scholar
    • Export Citation
  • 34.

    Morihisa, H.; Fukata, F.; Muro, H.; Nishimura, K.-I.; Makino, T. Determination of indapamide in human serum using 96-well solid-phase extraction and high-performance liquid chromatography-tandem mass spectrometry (LC-MS/MS). J. Chromatogr. B. 2008, 870, 126130. https://doi.org/10.1016/j.jchromb.2008.05.042.

    • Search Google Scholar
    • Export Citation
  • 35.

    Tang, J.; Li, J.; Sun, J.; Yin, J.; He, Z. Rapid and sensitive determination of indapamide in human blood by liquid chromatography with electrospray ionization mass spectrometric detection: application to a bioequivalence study. Pharmazie 2005, 60, 819822.

    • Search Google Scholar
    • Export Citation
  • 36.

    Tao, Y.; Wang, S.; Wang, L.; Song, M.; Hanga, T. Simultaneous determination of indapamide, perindopril and perindoprilat in human plasma or whole blood by UPLC-MS/MS and its pharmacokinetic application. J. Pharm. Anal 2018, 8, 333340. https://doi.org/10.1016/j.jpha.2018.05.004.

    • Search Google Scholar
    • Export Citation
  • 37.

    Mancia, G.; Laurent, S.; Agabiti-Rosei, E.; Ambrosioni, E.; Burnier, M.; Caulfield, M. J.; Cifkova, R.; Cle´ment, D.; Coca, A.; Dominiczak, A.; Erdine, S.; Fagard, R.; Farsang, C.; Grassi, G.; Haller, H.; Heagerty, A.; Kjeldsen, S. E.; Kiowski, W.; Mallion, J. M.; Manolis, A.; Narkiewicz, K.; Nilsson, P.; Olsen, M. H.; Rahn, K. H.; Redon, J.; Rodicio, J.; RuilopeaL.; Schmieder, R. E.; Struijker-Boudier, H. A. J.; van Zwieten, P. A.; Viigimaa, M.; Zanchetti, A. Reappraisal of European guidelines on hypertension management: a European Society of hypertension task force document. J. Hypertens. 2009, 27, 21212158. https://doi.org/10.1097/HJH.0b013e328333146d.

    • Search Google Scholar
    • Export Citation
  • 38.

    Nedogoda, S. V.; Stojanov, V. J. Single-pill combination of perindopril/indapamide/amlodipine in patients with uncontrolled hypertension: a randomized controlled trial. Cardiol. Ther. 2017, 6, 91104. https://doi.org/10.1007/s40119-017-0085-7.

    • Search Google Scholar
    • Export Citation
  • 39.

    Rezk, M.; Badr, K. A. Determination of amlodipine, indapamide and perindopril in human plasma by a novel LC-MS/MS method; Application to a bioequivalence study. Biomed. Chromatogr. 2020, 35, e5048. https://doi.org/10.1002/bmc.5048.

    • Search Google Scholar
    • Export Citation
  • 40.

    van Eeckhaut, A.; Lanckmans, K.; Sarre, S.; Smolders, I.; Michotte, Y. Validation of bioanalytical LC-MS/MS assays: evaluation of matrix effects. J. Chromatogr. B. 2009, 877, 21982207. https://doi.org/10.1016/j.jchromb.2009.01.003.

    • Search Google Scholar
    • Export Citation
  • 41.

    Macfadyen, R. J.; Lees, K. R.; Reid, J. L. Perindopril. A review of its pharmacokinetics and clinical pharmacology. Drugs 1990, 39 (Suppl 1), 4963. https://doi.org/10.2165/00003495-199000391-00009.

    • Search Google Scholar
    • Export Citation
  • 42.

    Vincent, M.; Marchand, B.; Rémond, G.; Jaguelin-Guinamant, S.; Damien, G.; Portevin, B.; Baumal, J. Y.; Volland, J. P.; Bouchet, J. P.; Lambert, P. H. Synthesis and ACE inhibitory activity of the stereoisomers of perindopril (S 9490) and perindoprilate (S 9780). Drug Des. Discov. 1992, 9, 1128.

    • Search Google Scholar
    • Export Citation
  • 43.

    Okamoto, Y.; Yashima, E. Polysaccharide derivatives for chromatographic separation of enantiomers. Angew. Chem. Int. Ed. Engl. 1998, 37, 10201043. https://doi.org/10.1002/(SICI)1521-3773(19980504)37:8<1020::AID-ANIE1020>3.0.CO;2-5.

    • Search Google Scholar
    • Export Citation
  • 44.

    Yashima, E. Polysaccharide-based chiral stationary phases for high performance liquid chromatographic enantioseparation. J. Chromatogr. A. 2001, 906, 105125. https://doi.org/10.1016/S0021-9673(00)00501-X.

    • Search Google Scholar
    • Export Citation
  • 45.

    Penmetsa, K. V.; Reddick, C. D.; Fink, S. W.; Kleintop, B. L.; DiDonato, G. C.; Volk, K. J.; Klohr, S. E. Development of reversed-phase chiral HPLC methods using mass spectrometry compatible mobile phases. J. Liq. Chrom. & Rel. Technol. 2000, 23, 831839. https://doi.org/10.1081/JLC-100101492.

    • Search Google Scholar
    • Export Citation
  • 46.

    Du, B.; Pang, L.; Li, H.; Ma, S.; Li, Y.; Jia, X.; Zhang, Z. Chiral liquid chromatography resolution and stereoselective pharmacokinetic study of indapamide enantiomers in rats. J. Chromatogr. B 2013, 932, 8891. https://doi.org/10.1016/j.jchromb.2013.06.007.

    • Search Google Scholar
    • Export Citation
  • 47.

    Pirkle, W. H.; Welch, C. J. An improved chiral stationary phase for the chromatographic separation of underivatized naproxen enantiomers. J. Liq. Chromatogr. 1992, 15, 19471955. https://doi.org/10.1080/10826079208020869; (W.H. Pirkle, C.J. Welch, B Lamm, Design, synthesis, and evaluation of an improved enantioselective naproxen selector, J. Org. Chem. 57 (1992) 3854-3860.https://doi.org/10.1021/jo00040a026).

    • Search Google Scholar
    • Export Citation
  • 48.

    Pirkle, W. H.; Welch, C. J. Use of simultaneous face to face and face to edge π-π interactions to facilitate chiral recognition. Tetrahedron Asymmetry 1994, 5, 777780. https://doi.org/10.1016/S0957-4166(00)86225-4.

    • Search Google Scholar
    • Export Citation
  • 49.

    Welch, C. J.; Szczerba, T.; Perrin, S. R. Some recent high-performance liquid chromatography separations of the enantiomers of pharmaceuticals and other compounds using the Whelk-O 1 chiral stationary phase. J. Chromatogr. 1997, 758, 9398. https://doi.org/10.1016/s0021-9673(96)00569-9.

    • Search Google Scholar
    • Export Citation
  • 50.

    Cârje, A. G., Ion, V., Muntean, D.-L., Hancu, G., Balint, A., Imre, S., Enantioseparation of indapamide by high performance liquid chromatography using ovomucoid glycoprotein as chiral selector. Farmacia 64 (2016) 181186 (A. G. Cârje, V. Ion, D.-L. Muntean, G. Hancu, A. Balint, V. Ion, S. Imre; Simultaneous chiral separation of perindopril erbumine and indapamide enantiomers by high performance liquid chromatography, Farmacia. 2017, Vol. 65 (2007) 900-907).

    • Search Google Scholar
    • Export Citation
  • 51.

    Cyclobond Handbook: A Guide to Using Cyclodextrin Bonded Phases for Chiral LC Separations, Advanced Separation Technologies, seventh ed., Whippany, NJ, 2005. Available from: https://www.sigmaaldrich.com/deepweb/assets/sigmaaldrich/marketing/global/documents/169/815/cyclobond_handbook.pdf.

    • Search Google Scholar
    • Export Citation
  • 52.

    Armstrong, D. W.; Stalcup, A. M.; Hilton, M. L.; Duncan, J. D.; Faulkner, J. R. Jr.; Chang, S.-C. Derivatized cyclodextrins for normal-phase liquid chromatographic separation of enantiomers. Anal. Chem. 1990, 62, 16101615. https://doi.org/10.1021/ac00214a014.

    • Search Google Scholar
    • Export Citation
  • 53.

    Okamoto, Y.; Aburatani, R.; Hatada, K. Chromatographic chiral resolution: XIV. Cellulose tribenzoate derivatives as chiral stationary phases for high-performance liquid chromatography. J. Chromatogr. 1987, 389, 95102. https://doi.org/10.1016/S0021-9673(01)94414-0.

    • Search Google Scholar
    • Export Citation
  • 54.

    Okamoto, Y.; Aburatani, R.; Hatada, K. Direct chromatographic separation of 2-arylpropionic acid enantiomers using tris(3,5-dimethylphenylcarbamate)s of cellulose and amylose as chiral stationary phases. Chirality 1989, 1, 239242. https://doi.org/10.1002/chir.530010310.

    • Search Google Scholar
    • Export Citation
  • 55.

    Armstrong, D. W.; Chang, C.-D.; Lee, S. H. (R)-and (S)-Naphthylethylcarbamate-substituted β-cyclodextrin bonded stationary phases for the reversed-phase liquid chromatographic separation of enantiomers. J. Chromatogr. 1991, 539, 8390. https://doi.org/10.1016/S0021-9673(01)95362-2.

    • Search Google Scholar
    • Export Citation
  • 56.

    Zhong, Q.; He, L.; Beesley, T. E.; Trahanovsky, W. S.; Sun, P.; Wang, C.; Armstrong, D. W. Development of dinitrophenylated cyclodextrin derivatives for enhanced enantiomeric separations by high-performance liquid chromatography. J. Chromatogr. A. 2006, 1115, 1945. https://doi.org/10.1016/j.chroma.2006.02.065.

    • Search Google Scholar
    • Export Citation
  • 57.

    Qi Wang, R.; Ong, T.-T.; Tang, W.; Ng, S.-C. Cationic cyclodextrins chemically-bonded chiral stationary phases for high-performance liquid chromatography. Anal. Chim. Acta 2012, 718, 121129. https://doi.org/10.1016/j.aca.2011.12.063.

    • Search Google Scholar
    • Export Citation
  • 58.

    Liu, T.; Han, L.; Yu, Z.; Zhang, D.; Liu, C. Theoretical and experimental study on the molecular recognition of adrenaline by supramolecular complexation with crown ethers. Comput. Biol. Med. 2012, 42, 480484. https://doi.org/10.1016/j.compbiomed.2011.12.017.

    • Search Google Scholar
    • Export Citation
  • 59.

    Gong, Y.; Xiang, Y.; Yue, B. Application of diaza-18-crown-6-capped beta-cyclodextrin bonded silica particles as chiral stationary phases for ultrahigh pressure capillary liquid chromatography. J. Chromatogr. A. 2003, 1002, 6370. https://doi.org/10.1016/S0021-9673(03)00732-5.

    • Search Google Scholar
    • Export Citation
  • 60.

    Berkecz, R.; Németi, G.; Péter, A.; Ilisz, I. Liquid chromatographic enantioseparations utilizing chiral stationary phases based on crown ethers and cyclofructans. Molecules 2021, 26, 4648. https://doi.org/10.3390/molecules26154648.

    • Search Google Scholar
    • Export Citation
  • 61.

    Thamarai Chelvi, S. K.; Zhaoa, J.; Chen, L.; Yan, S.; Yin, X.; Sun, J.; Yong, E. L.; Wei, Q.; Gong, Y. Preparation and characterization of 4-isopropylcalix[4]arene-capped (3-(2-O-β-cyclodextrin)-2-hydroxypropoxy)-propylsilyl-appended silica particles as chiral stationary phase for high-performance liquid chromatography. J. Chromatogr. A. 2014, 1324, 104108. https://doi.org/10.1016/j.chroma.2013.11.025.

    • Search Google Scholar
    • Export Citation
  • 62.

    Thamarai Chelvi, S. K.; Yong, E. L.; Gong, Y. H. Preparation and evaluation of calix[4]arene-capped β-cyclodextrin-bonded silica particles as chiral stationary phase for high-performance liquid chromatography. J. Chromatogr. A. 2008, 1203, 5458. https://doi.org/10.1016/j.chroma.2008.07.021.

    • Search Google Scholar
    • Export Citation
  • 63.

    Ma, M.; Wei, Q.; Meng, M.; Yin, J.; Shan, Y.; Du, L.; Zhu, X.; SohS. F.; Min, M.; Zhou, X.; Yin, X.; Gong, Y. Preparation and application of aza-15-crown-5-capped aethylcalix[4]resorcinarene-bonded silica particles for use as chiral stationary phase in HPLC. Chromatographia 2017, 80, 10071014. https://doi.org/10.1007/s10337-017-3312-4.

    • Search Google Scholar
    • Export Citation
  • 64.

    Tan, H. M.; Soh, S. F.; Zhao, J.; Yong, E. L.; Gong, Y. Preparation and application of methylcalix[4]resorcinarene-bonded silica particles as chiral stationary phase in high-performance liquid chromatography. Chirality 2011, 23(Suppl 1(1E)), E91E97. https://doi.org/10.1002/chir.20983.

    • Search Google Scholar
    • Export Citation
  • 65.

    Dittmann, M. M.; Rozing, G. P. Capillary electrochromatography -a high-efficiency micro-separation technique. J. Chromatogr. A. 1996, 744, 6374. https://doi.org/10.1016/0021-9673(96)00382-2.

    • Search Google Scholar
    • Export Citation
  • 66.

    Cikalo, M. G.; Bartle, K. D.; Robson, M. M.; Myers, P.; Euerby, M. R. Capillary electrochromatography. Analyst 1998, 123, 87102. https://doi.org/10.1039/a801148f.

    • Search Google Scholar
    • Export Citation
  • 67.

    Krause, K.; Girod, M.; Chankvetadze, B.; Blaschke, G. Enantioseparations in normal- and reversed-phase nano-high-performance liquid chromatography and capillary electrochromatography using polyacrylamide and polysaccharide derivatives as chiral stationary phases. J. Chromatogr. A. 1999, 837, 5163. https://doi.org/10.1016/S0021-9673(99)00075-8.

    • Search Google Scholar
    • Export Citation
  • 68.

    Francotte, E. Contribution of preparative chromatographic resolution to the investigation of chiral phenomena. J. Chromatogr. A. 1994, 666, 565601. https://doi.org/10.1016/0021-9673(94)80419-2.

    • Search Google Scholar
    • Export Citation
  • 69.

    Francotte, E.; Jung, M. Enantiomer separation by open-tubular liquid chromatography and electrochromatography in cellulose-coated capillaries. Chromatographia 1996, 42, 521527. https://doi.org/10.1007/BF02290286.

    • Search Google Scholar
    • Export Citation
  • 70.

    Mayer, S.; Briand, X.; Francotte, E. Separation of enantiomers by packed capillary electrochromatography on a cellulose-based stationary phase. J. Chromatogr. A. 2000, 875, 331339. https://doi.org/10.1016/s0021-9673(99)01335-7.

    • Search Google Scholar
    • Export Citation
  • 71.

    Otsuka, K.; Mikami, C.; Terabe, S. Enantiomer separations by capillary electrochromatography using chiral stationary phases. J. Chromatogr. A. 2000, 887, 457463. https://doi.org/10.1016/S0021-9673(99)01205-4.

    • Search Google Scholar
    • Export Citation
  • 72.

    Kawamura, K.; Otsuka, K.; Terabe, S. Capillary electrochromatographic enantioseparations using a packed capillary with a 3 μm OD-type chiral packing. J. Chromatogr. A. 2001, 924, 251257. https://doi.org/10.1016/s0021-9673(01)00902-5.

    • Search Google Scholar
    • Export Citation
  • 73.

    Girod, M.; Chankvetadze, B.; Blaschke, G. Enantioseparations in non-aqueous capillary electrochromatography using polysaccharide type chiral stationary phases. J. Chromatogr. A. 2000, 887, 439455. https://doi.org/10.1016/S0021-9673(99)01204-2.

    • Search Google Scholar
    • Export Citation
  • 74.

    Wang, R.-Q.; Ong, T.-T.; Ng, S.-C. Chemically bonded cationic β-cyclodextrin derivatives and their applications in supercritical fluid chromatography. J. Chromatogr. A. 2012, 1224, 97103. https://doi.org/10.1016/j.chroma.2011.12.053.

    • Search Google Scholar
    • Export Citation
  • 75.

    Williams, K. L.; Sander, L. C.; Wise, S. A. Comparison of liquid and supercritical fluid chromatography using naphthylethylcarbamoylated-β-cyclodextrin chiral stationary phases. J. Chromatogr. A. 1996, 746, 91101. https://doi.org/10.1016/0021-9673(96)00291-9.

    • Search Google Scholar
    • Export Citation
  • 76.

    Folprechtová, D.; Kalíková, K. Macrocyclic glycopeptide-based chiral selectors for enantioseparation in sub/supercritical fluid chromatography. Anal. Sci. Adv. 2020, 2, 1532. https://doi.org/10.1002/ansa.202000099.

    • Search Google Scholar
    • Export Citation
  • 77.

    Phinney, K. W.; Sander, L. C. Preliminary evaluation of a standard reference material for chiral stationary phases used in liquid and supercritical fluid chromatography. Anal. Bioanal. Chem. 2002, 372, 101108. https://doi.org/10.1007/s00216-001-1198-2.

    • Search Google Scholar
    • Export Citation
  • 78.

    Phinney, K. W.; Sander, L. C. Additive concentration effects on enantioselective separations in supercritical fluid chromatography. Chirality 2003, 15, 287294. https://doi.org/10.1002/chir.10196.

    • Search Google Scholar
    • Export Citation
  • 1.

    Chaffman, M.; Heel, R. C.; Brodgen, R. N.; Speight, T. M.; Avery, G. S. Indapamide: a review of its pharmacodynamic properties and therapeutic efficacy in hypertension. Drugs 1984, 28, 189235. https://doi.org/10.2165/00003495-198428030-00001.

    • Search Google Scholar
    • Export Citation
  • 2.

    FDA’s policy statement for the development of new stereoisomeric drugs, Chirality 1992, 4, 338340. https://doi.org/10.1002/chir.530040513.

    • Search Google Scholar
    • Export Citation
  • 3.

    EMA Investigation of chiral active substances (human) European Medicines Agency, 2018. [cited 2022 Jul 25]. Available from: https://www.ema.europa.eu/en/investigation-chiral-active-substances.

    • Search Google Scholar
    • Export Citation
  • 4.

    Patil, N. B.; Patil, K. B.; Wagh, M. N.; Patil, A. A. A review on analytical method for determination of indapamide in marketed pharmaceutical preparation. Pharma Tutor 2018, 6, 7988. https://doi.org/10.29161/PT.v6.i12.2018.79.

    • Search Google Scholar
    • Export Citation
  • 5.

    Tero-Vescan, A.; Hancu, G.; Oroian, M.; Cârje, A. Chiral separation of indapamide enantiomers by capillary electrophoresis. Adv. Pharm. Bull. 2014, 4, 267272. https://doi.org/10.5681/apb.2014.039.

    • Search Google Scholar
    • Export Citation
  • 6.

    Bataillard, A.; Schiavi, P.; Sassard, J. Pharmacological properties of indapamide: rationale for use in hypertension. Clin. Pharmacokinet. 1999, 37(Supplement 1), 712. https://doi.org/10.2165/00003088-199937001-00002.

    • Search Google Scholar
    • Export Citation
  • 7.

    Uehara, Y.; Shirahase, H.; Nagata, T.; Ishimitsu, T.; Morishita, S.; Osumi, S.; Matsuoka, H.; Sugimoto, T. Radical scavengers of indapamide in prostacyclin synthesis in rat smooth muscle cell. Hypertension 1990, 15, 216224. https://doi.org/10.1161/01.HYP.15.2.216.

    • Search Google Scholar
    • Export Citation
  • 8.

    Choi, R. L.; Rosenberg, M. E.; Grebow, P.; Huntley, T. E. High-performance liquid chromatographic analysis of indapamide (RHC 2555) in urine, plasma and blood. J. Chromatogr. 1982, 230, 181187. https://doi.org/10.1016/s0378-4347(00)81447-4.

    • Search Google Scholar
    • Export Citation
  • 9.

    Brent Miller, R.; Dadgar, D.; Lalande, M. High-performance liquid chromatographic method for the determination of indapamide in human whole blood. J. Chromatogr. 1993, 614, 293298. https://doi.org/10.1016/0378-4347(93)80321-T.

    • Search Google Scholar
    • Export Citation
  • 10.

    Legorburu, M. J.; Alonso, R. M.; Jimenez, R. M.; Ortiz, E. Quantitative determination of indapamide in pharmaceuticals and urine by high-performance liquid chromatography with amperometric detection. J. Chromatogr. Sci. 1999, 37, 283287. https://doi.org/10.1093/chromsci/37.8.283.

    • Search Google Scholar
    • Export Citation
  • 11.

    Pietta, P.; Calatroni, A.; Rava, A. High-performance liquid chromatographic assay for monitoring indapamide and its major metabolite in urine. J. Chromatogr. B. 1982, 228, 377381. https://doi.org/10.1016/S0378-4347(00)80458-2.

    • Search Google Scholar
    • Export Citation
  • 12.

    Hang, T.-J.; Zhao, W.; Liu, J.; Song, M.; Xie, Y.; Zhang, Z.; Shen, J.; Zhang, Y. A selective HPLC method for the determination of indapamide in human whole blood: application to a bioequivalence study in Chinese volunteers. J. Pharm. Biomed. Anal. 2006, 40, 202205. https://doi.org/10.1016/j.jpba.2005.06.035.

    • Search Google Scholar
    • Export Citation
  • 13.

    Ventura, R.; Segura, J. Detection of diuretic agents in doping control. J. Chromatogr. B 1996, 687, 127144. https://doi.org/10.1016/S0378-4347(96)00279-4.

    • Search Google Scholar
    • Export Citation
  • 14.

    Ja Park, S.; Pyo, H.-S.; Kim, Y.-J.; Kim, M.-S.; Park, J. Systematic analysis of diuretic doping agents by HPLC screening and GC/MS confirmation. J. Anal. Toxicol. 1990, 14, 8490. https://doi.org/10.1093/jat/14.2.84.

    • Search Google Scholar
    • Export Citation
  • 15.

    Lisi, A. M.; Kazlauskas, R.; Trout, G. J. Diuretic screening in human urine by gas chromatography-mass spectrometry: use of a macroreticular acrylic copolymer for the efficient removal of the coextracted phase-transfer reagent after derivatization by direct extractive alkylation. J. Chromatogr. B. 1992, 581, 5763. https://doi.org/10.1016/0378-4347(92)80447-X.

    • Search Google Scholar
    • Export Citation
  • 16.

    Amendola, L.; Colamonici, C.; Mazzarino, M.; Botre, F. Rapid determination of diuretics in human urine by gas chromatography–mass spectrometry following microwave assisted derivatization. Anal. Chim. Acta 2003, 475, 125136. https://doi.org/10.1016/S0003-2670(02)01223-0.

    • Search Google Scholar
    • Export Citation
  • 17.

    Zendelovska, D.; Stafilov, T.; Stefova, M. Optimization of a solid-phase extraction method for determination of indapamide in biological fluids using high-performance liquid chromatography. J. Chromatogr. B. 2003, 788, 199206. https://doi.org/10.1016/S1570-0232(02)01017-6.

    • Search Google Scholar
    • Export Citation
  • 18.

    Deventer, K.; Delbeke, F. T.; Roels, K.; Eenoo, P. V. Screening for 18 diuretics and probenecid in doping analysis by liquid chromatography–tandem mass spectrometry. Biomed. Chromatogr. 2002, 16, 529535. https://doi.org/10.1002/bmc.201.

    • Search Google Scholar
    • Export Citation
  • 19.

    Cooper, S. F.; Massé, R.; Dugal, R. Comprehensive screening procedure for diuretics in urine by high-performance liquid chromatography. J. Chromatogr. B. 1989, 489, 6588. https://doi.org/10.1016/S0378-4347(00)82884-4.

    • Search Google Scholar
    • Export Citation
  • 20.

    Tsai, F. Y.; Lui, L. F.; Chang, B. Analysis of diuretic doping agents by HPLC screening and GC-MSD confirmation. J. Pharm. Biomed. Anal. 1991, 9, 10691076. https://doi.org/10.1016/0731-7085(91)80046-C.

    • Search Google Scholar
    • Export Citation
  • 21.

    Carreras, D.; Imaz, C.; Navajas, R.; Garcia, M. A.; Rodriguez, C.; Rodriguez, A. F.; Cortes, R. Comparison of derivatization procedures for the determination of diuretics in urine by gas chromatography-mass spectrometry. J. Chromatogr. A. 1994, 683, 195202. https://doi.org/10.1016/S0021-9673(94)89116-8.

    • Search Google Scholar
    • Export Citation
  • 22.

    Goebel, C.; Trout, G.; Kazlauskas, R. Rapid screening method for diuretics in doping control using auto-mated solid phase extraction and liqud chromatography-electrospray tandem mass spectrometry. Analytica Chim. Acta 2004, 502, 6574. https://doi.org/10.1016/j.aca.2003.09.062.

    • Search Google Scholar
    • Export Citation
  • 23.

    Albu, F.; Georgita, C.; David, V.; Medvedovici, A. Liquid chromatography-electrospray tandem mass spectrometry method for determination of indapamide in serum for single/multiple dose bioequivalence studies of sustained release formulations. J. Chromatogr. B. 2005, 816, 3540. https://doi.org/10.1016/j.jchromb.2004.11.002.

    • Search Google Scholar
    • Export Citation
  • 24.

    Gao, X. L.; Chen, J.; Mei, N.; Tao, W. X.; Jiang, W. M.; Jiang, X. G. HPLC determination and pharmacokinetic study of indapamide in human whole blood. Chromatographia 2005, 61, 581585. https://doi.org/10.1365/S10337-005-0548-1.

    • Search Google Scholar
    • Export Citation
  • 25.

    Jain, D. S.; Subbaiah, G.; Sanyal, M.; Pande, U. C.; Shrivastav, P. Liquid chromatography–tandem mass spectrometry validated method for the estimation of indapamide in human whole blood. J. Chromatogr. B. 2006, 834, 149154. https://doi.org/10.1016/j.jchromb.2006.02.040.

    • Search Google Scholar
    • Export Citation
  • 26.

    Ding, L.; Yang, L.; Liu, F.; Ju, W.; Xiong, N. A sensitive LC-ESI-MS method for the determination of indapamide in human plasma: method and clinical applications. J. Pharm. Biomed. Anal. 2006, 42, 213217. https://doi.org/10.1016/j.jpba.2006.03.039.

    • Search Google Scholar
    • Export Citation
  • 27.

    Ateş, Z.; Özden, T.; Özilhan, S.; Eren, S. Improved ultra-performance LC determination of indapamide in human plasma. Chromatographia 2007, 66, 119122. https://doi.org/10.1365/s10337-007-0300-0.

    • Search Google Scholar
    • Export Citation
  • 28.

    Li, G.; Zhang, X.; Tian, Y.; Zhang, Z.; Rui, J.; Chu, X. Pharmacokinetics and bioequivalence study of two indapamide formulations after single dose administration in healthy Chinese male volunteers. Drug Res. 2013, 63, 1318. https://doi.org/10.1055/s-0032-1331181.

    • Search Google Scholar
    • Export Citation
  • 29.

    Nakov, N.; Mladenovska, K.; Labacevski, N.; Dimovski, A.; Petkovska, R.; Dimitrovska, A.; Kavrakovski, Z. Development and validation of automated SPE-LC-MS/MS method for determination of indapamide in human whole blood and its application to real study samples. Biomed. Chromatogr. 2013, 27, 15401546. https://doi.org/10.1002/bmc.2957.

    • Search Google Scholar
    • Export Citation
  • 30.

    Ramkumar, A.; Ponnusamy, V. K.; Jen-Fon, J. Rapid determination of indapamide in human urine using novel low-density solvent based ultrasound assisted emulsification microextraction coupled with high performance liquid chromatography-variable wavelength detection. Anal. Methods 2013, 5, 2572. https://doi.org/10.1039/c3ay40187a.

    • Search Google Scholar
    • Export Citation
  • 31.

    Regueiro, J.; Llompart, M.; Garcia-Jares, C.; Garcia-Monteagudo, J. C.; Cela, R. Ultrasound-assisted emulsification-microextraction of emergent contaminants and pesticides in environmental waters. J. Chromatogr. A. 2008, 1190, 2738. https://doi.org/10.1016/j.chroma.2008.02.091.

    • Search Google Scholar
    • Export Citation
  • 32.

    Pinto, G. A.; Pastre, K. I. F.; Bellorio, K. B.; deSouza Teixeira, L.; Carlo deSouza, W.; deAbreu, F. C.; Cardoso, F. F. deS. e S.; Pianetti, G. A.; César, I. C. An improved LC-MS/MS method for quantitation of indapamide in whole blood: application for a bioequivalence study. Biomed. Chromatogr. 2014, 28, 12121218. https://doi.org/10.1002/bmc.3148.

    • Search Google Scholar
    • Export Citation
  • 33.

    Chen, W.; Liang, Y.; Zhang, H.; Xiong, H. Y.; Xie, W. G. Simple, sensitive and rapid LC-MS method for the indapamide in human plasma- application to pharmacokinetic. J. Chromatogr. B. 2006, 842, 5863. https://doi.org/10.1016/j.jchromb.2006.03.024.

    • Search Google Scholar
    • Export Citation
  • 34.

    Morihisa, H.; Fukata, F.; Muro, H.; Nishimura, K.-I.; Makino, T. Determination of indapamide in human serum using 96-well solid-phase extraction and high-performance liquid chromatography-tandem mass spectrometry (LC-MS/MS). J. Chromatogr. B. 2008, 870, 126130. https://doi.org/10.1016/j.jchromb.2008.05.042.

    • Search Google Scholar
    • Export Citation
  • 35.

    Tang, J.; Li, J.; Sun, J.; Yin, J.; He, Z. Rapid and sensitive determination of indapamide in human blood by liquid chromatography with electrospray ionization mass spectrometric detection: application to a bioequivalence study. Pharmazie 2005, 60, 819822.

    • Search Google Scholar
    • Export Citation
  • 36.

    Tao, Y.; Wang, S.; Wang, L.; Song, M.; Hanga, T. Simultaneous determination of indapamide, perindopril and perindoprilat in human plasma or whole blood by UPLC-MS/MS and its pharmacokinetic application. J. Pharm. Anal 2018, 8, 333340. https://doi.org/10.1016/j.jpha.2018.05.004.

    • Search Google Scholar
    • Export Citation
  • 37.

    Mancia, G.; Laurent, S.; Agabiti-Rosei, E.; Ambrosioni, E.; Burnier, M.; Caulfield, M. J.; Cifkova, R.; Cle´ment, D.; Coca, A.; Dominiczak, A.; Erdine, S.; Fagard, R.; Farsang, C.; Grassi, G.; Haller, H.; Heagerty, A.; Kjeldsen, S. E.; Kiowski, W.; Mallion, J. M.; Manolis, A.; Narkiewicz, K.; Nilsson, P.; Olsen, M. H.; Rahn, K. H.; Redon, J.; Rodicio, J.; RuilopeaL.; Schmieder, R. E.; Struijker-Boudier, H. A. J.; van Zwieten, P. A.; Viigimaa, M.; Zanchetti, A. Reappraisal of European guidelines on hypertension management: a European Society of hypertension task force document. J. Hypertens. 2009, 27, 21212158. https://doi.org/10.1097/HJH.0b013e328333146d.

    • Search Google Scholar
    • Export Citation
  • 38.

    Nedogoda, S. V.; Stojanov, V. J. Single-pill combination of perindopril/indapamide/amlodipine in patients with uncontrolled hypertension: a randomized controlled trial. Cardiol. Ther. 2017, 6, 91104. https://doi.org/10.1007/s40119-017-0085-7.

    • Search Google Scholar
    • Export Citation
  • 39.

    Rezk, M.; Badr, K. A. Determination of amlodipine, indapamide and perindopril in human plasma by a novel LC-MS/MS method; Application to a bioequivalence study. Biomed. Chromatogr. 2020, 35, e5048. https://doi.org/10.1002/bmc.5048.

    • Search Google Scholar
    • Export Citation
  • 40.

    van Eeckhaut, A.; Lanckmans, K.; Sarre, S.; Smolders, I.; Michotte, Y. Validation of bioanalytical LC-MS/MS assays: evaluation of matrix effects. J. Chromatogr. B. 2009, 877, 21982207. https://doi.org/10.1016/j.jchromb.2009.01.003.

    • Search Google Scholar
    • Export Citation
  • 41.

    Macfadyen, R. J.; Lees, K. R.; Reid, J. L. Perindopril. A review of its pharmacokinetics and clinical pharmacology. Drugs 1990, 39 (Suppl 1), 4963. https://doi.org/10.2165/00003495-199000391-00009.

    • Search Google Scholar
    • Export Citation
  • 42.

    Vincent, M.; Marchand, B.; Rémond, G.; Jaguelin-Guinamant, S.; Damien, G.; Portevin, B.; Baumal, J. Y.; Volland, J. P.; Bouchet, J. P.; Lambert, P. H. Synthesis and ACE inhibitory activity of the stereoisomers of perindopril (S 9490) and perindoprilate (S 9780). Drug Des. Discov. 1992, 9, 1128.

    • Search Google Scholar
    • Export Citation
  • 43.

    Okamoto, Y.; Yashima, E. Polysaccharide derivatives for chromatographic separation of enantiomers. Angew. Chem. Int. Ed. Engl. 1998, 37, 10201043. https://doi.org/10.1002/(SICI)1521-3773(19980504)37:8<1020::AID-ANIE1020>3.0.CO;2-5.

    • Search Google Scholar
    • Export Citation
  • 44.

    Yashima, E. Polysaccharide-based chiral stationary phases for high performance liquid chromatographic enantioseparation. J. Chromatogr. A. 2001, 906, 105125. https://doi.org/10.1016/S0021-9673(00)00501-X.

    • Search Google Scholar
    • Export Citation
  • 45.

    Penmetsa, K. V.; Reddick, C. D.; Fink, S. W.; Kleintop, B. L.; DiDonato, G. C.; Volk, K. J.; Klohr, S. E. Development of reversed-phase chiral HPLC methods using mass spectrometry compatible mobile phases. J. Liq. Chrom. & Rel. Technol. 2000, 23, 831839. https://doi.org/10.1081/JLC-100101492.

    • Search Google Scholar
    • Export Citation
  • 46.

    Du, B.; Pang, L.; Li, H.; Ma, S.; Li, Y.; Jia, X.; Zhang, Z. Chiral liquid chromatography resolution and stereoselective pharmacokinetic study of indapamide enantiomers in rats. J. Chromatogr. B 2013, 932, 8891. https://doi.org/10.1016/j.jchromb.2013.06.007.

    • Search Google Scholar
    • Export Citation
  • 47.

    Pirkle, W. H.; Welch, C. J. An improved chiral stationary phase for the chromatographic separation of underivatized naproxen enantiomers. J. Liq. Chromatogr. 1992, 15, 19471955. https://doi.org/10.1080/10826079208020869; (W.H. Pirkle, C.J. Welch, B Lamm, Design, synthesis, and evaluation of an improved enantioselective naproxen selector, J. Org. Chem. 57 (1992) 3854-3860.https://doi.org/10.1021/jo00040a026).

    • Search Google Scholar
    • Export Citation
  • 48.

    Pirkle, W. H.; Welch, C. J. Use of simultaneous face to face and face to edge π-π interactions to facilitate chiral recognition. Tetrahedron Asymmetry 1994, 5, 777780. https://doi.org/10.1016/S0957-4166(00)86225-4.

    • Search Google Scholar
    • Export Citation
  • 49.

    Welch, C. J.; Szczerba, T.; Perrin, S. R. Some recent high-performance liquid chromatography separations of the enantiomers of pharmaceuticals and other compounds using the Whelk-O 1 chiral stationary phase. J. Chromatogr. 1997, 758, 9398. https://doi.org/10.1016/s0021-9673(96)00569-9.

    • Search Google Scholar
    • Export Citation
  • 50.

    Cârje, A. G., Ion, V., Muntean, D.-L., Hancu, G., Balint, A., Imre, S., Enantioseparation of indapamide by high performance liquid chromatography using ovomucoid glycoprotein as chiral selector. Farmacia 64 (2016) 181186 (A. G. Cârje, V. Ion, D.-L. Muntean, G. Hancu, A. Balint, V. Ion, S. Imre; Simultaneous chiral separation of perindopril erbumine and indapamide enantiomers by high performance liquid chromatography, Farmacia. 2017, Vol. 65 (2007) 900-907).

    • Search Google Scholar
    • Export Citation
  • 51.

    Cyclobond Handbook: A Guide to Using Cyclodextrin Bonded Phases for Chiral LC Separations, Advanced Separation Technologies, seventh ed., Whippany, NJ, 2005. Available from: https://www.sigmaaldrich.com/deepweb/assets/sigmaaldrich/marketing/global/documents/169/815/cyclobond_handbook.pdf.

    • Search Google Scholar
    • Export Citation
  • 52.

    Armstrong, D. W.; Stalcup, A. M.; Hilton, M. L.; Duncan, J. D.; Faulkner, J. R. Jr.; Chang, S.-C. Derivatized cyclodextrins for normal-phase liquid chromatographic separation of enantiomers. Anal. Chem. 1990, 62, 16101615. https://doi.org/10.1021/ac00214a014.

    • Search Google Scholar
    • Export Citation
  • 53.

    Okamoto, Y.; Aburatani, R.; Hatada, K. Chromatographic chiral resolution: XIV. Cellulose tribenzoate derivatives as chiral stationary phases for high-performance liquid chromatography. J. Chromatogr. 1987, 389, 95102. https://doi.org/10.1016/S0021-9673(01)94414-0.

    • Search Google Scholar
    • Export Citation
  • 54.

    Okamoto, Y.; Aburatani, R.; Hatada, K. Direct chromatographic separation of 2-arylpropionic acid enantiomers using tris(3,5-dimethylphenylcarbamate)s of cellulose and amylose as chiral stationary phases. Chirality 1989, 1, 239242. https://doi.org/10.1002/chir.530010310.

    • Search Google Scholar
    • Export Citation
  • 55.

    Armstrong, D. W.; Chang, C.-D.; Lee, S. H. (R)-and (S)-Naphthylethylcarbamate-substituted β-cyclodextrin bonded stationary phases for the reversed-phase liquid chromatographic separation of enantiomers. J. Chromatogr. 1991, 539, 8390. https://doi.org/10.1016/S0021-9673(01)95362-2.

    • Search Google Scholar
    • Export Citation
  • 56.

    Zhong, Q.; He, L.; Beesley, T. E.; Trahanovsky, W. S.; Sun, P.; Wang, C.; Armstrong, D. W. Development of dinitrophenylated cyclodextrin derivatives for enhanced enantiomeric separations by high-performance liquid chromatography. J. Chromatogr. A. 2006, 1115, 1945. https://doi.org/10.1016/j.chroma.2006.02.065.

    • Search Google Scholar
    • Export Citation
  • 57.

    Qi Wang, R.; Ong, T.-T.; Tang, W.; Ng, S.-C. Cationic cyclodextrins chemically-bonded chiral stationary phases for high-performance liquid chromatography. Anal. Chim. Acta 2012, 718, 121129. https://doi.org/10.1016/j.aca.2011.12.063.

    • Search Google Scholar
    • Export Citation
  • 58.

    Liu, T.; Han, L.; Yu, Z.; Zhang, D.; Liu, C. Theoretical and experimental study on the molecular recognition of adrenaline by supramolecular complexation with crown ethers. Comput. Biol. Med. 2012, 42, 480484. https://doi.org/10.1016/j.compbiomed.2011.12.017.

    • Search Google Scholar
    • Export Citation
  • 59.

    Gong, Y.; Xiang, Y.; Yue, B. Application of diaza-18-crown-6-capped beta-cyclodextrin bonded silica particles as chiral stationary phases for ultrahigh pressure capillary liquid chromatography. J. Chromatogr. A. 2003, 1002, 6370. https://doi.org/10.1016/S0021-9673(03)00732-5.

    • Search Google Scholar
    • Export Citation
  • 60.

    Berkecz, R.; Németi, G.; Péter, A.; Ilisz, I. Liquid chromatographic enantioseparations utilizing chiral stationary phases based on crown ethers and cyclofructans. Molecules 2021, 26, 4648. https://doi.org/10.3390/molecules26154648.

    • Search Google Scholar
    • Export Citation
  • 61.

    Thamarai Chelvi, S. K.; Zhaoa, J.; Chen, L.; Yan, S.; Yin, X.; Sun, J.; Yong, E. L.; Wei, Q.; Gong, Y. Preparation and characterization of 4-isopropylcalix[4]arene-capped (3-(2-O-β-cyclodextrin)-2-hydroxypropoxy)-propylsilyl-appended silica particles as chiral stationary phase for high-performance liquid chromatography. J. Chromatogr. A. 2014, 1324, 104108. https://doi.org/10.1016/j.chroma.2013.11.025.

    • Search Google Scholar
    • Export Citation
  • 62.

    Thamarai Chelvi, S. K.; Yong, E. L.; Gong, Y. H. Preparation and evaluation of calix[4]arene-capped β-cyclodextrin-bonded silica particles as chiral stationary phase for high-performance liquid chromatography. J. Chromatogr. A. 2008, 1203, 5458. https://doi.org/10.1016/j.chroma.2008.07.021.

    • Search Google Scholar
    • Export Citation
  • 63.

    Ma, M.; Wei, Q.; Meng, M.; Yin, J.; Shan, Y.; Du, L.; Zhu, X.; SohS. F.; Min, M.; Zhou, X.; Yin, X.; Gong, Y. Preparation and application of aza-15-crown-5-capped aethylcalix[4]resorcinarene-bonded silica particles for use as chiral stationary phase in HPLC. Chromatographia 2017, 80, 10071014. https://doi.org/10.1007/s10337-017-3312-4.

    • Search Google Scholar
    • Export Citation
  • 64.

    Tan, H. M.; Soh, S. F.; Zhao, J.; Yong, E. L.; Gong, Y. Preparation and application of methylcalix[4]resorcinarene-bonded silica particles as chiral stationary phase in high-performance liquid chromatography. Chirality 2011, 23(Suppl 1(1E)), E91E97. https://doi.org/10.1002/chir.20983.

    • Search Google Scholar
    • Export Citation
  • 65.

    Dittmann, M. M.; Rozing, G. P. Capillary electrochromatography -a high-efficiency micro-separation technique. J. Chromatogr. A. 1996, 744, 6374. https://doi.org/10.1016/0021-9673(96)00382-2.

    • Search Google Scholar
    • Export Citation
  • 66.

    Cikalo, M. G.; Bartle, K. D.; Robson, M. M.; Myers, P.; Euerby, M. R. Capillary electrochromatography. Analyst 1998, 123, 87102. https://doi.org/10.1039/a801148f.

    • Search Google Scholar
    • Export Citation
  • 67.

    Krause, K.; Girod, M.; Chankvetadze, B.; Blaschke, G. Enantioseparations in normal- and reversed-phase nano-high-performance liquid chromatography and capillary electrochromatography using polyacrylamide and polysaccharide derivatives as chiral stationary phases. J. Chromatogr. A. 1999, 837, 5163. https://doi.org/10.1016/S0021-9673(99)00075-8.

    • Search Google Scholar
    • Export Citation
  • 68.

    Francotte, E. Contribution of preparative chromatographic resolution to the investigation of chiral phenomena. J. Chromatogr. A. 1994, 666, 565601. https://doi.org/10.1016/0021-9673(94)80419-2.

    • Search Google Scholar
    • Export Citation
  • 69.

    Francotte, E.; Jung, M. Enantiomer separation by open-tubular liquid chromatography and electrochromatography in cellulose-coated capillaries. Chromatographia 1996, 42, 521527. https://doi.org/10.1007/BF02290286.

    • Search Google Scholar
    • Export Citation
  • 70.

    Mayer, S.; Briand, X.; Francotte, E. Separation of enantiomers by packed capillary electrochromatography on a cellulose-based stationary phase. J. Chromatogr. A. 2000, 875, 331339. https://doi.org/10.1016/s0021-9673(99)01335-7.

    • Search Google Scholar
    • Export Citation
  • 71.

    Otsuka, K.; Mikami, C.; Terabe, S. Enantiomer separations by capillary electrochromatography using chiral stationary phases. J. Chromatogr. A. 2000, 887, 457463. https://doi.org/10.1016/S0021-9673(99)01205-4.

    • Search Google Scholar
    • Export Citation
  • 72.

    Kawamura, K.; Otsuka, K.; Terabe, S. Capillary electrochromatographic enantioseparations using a packed capillary with a 3 μm OD-type chiral packing. J. Chromatogr. A. 2001, 924, 251257. https://doi.org/10.1016/s0021-9673(01)00902-5.

    • Search Google Scholar
    • Export Citation
  • 73.

    Girod, M.; Chankvetadze, B.; Blaschke, G. Enantioseparations in non-aqueous capillary electrochromatography using polysaccharide type chiral stationary phases. J. Chromatogr. A. 2000, 887, 439455. https://doi.org/10.1016/S0021-9673(99)01204-2.

    • Search Google Scholar
    • Export Citation
  • 74.

    Wang, R.-Q.; Ong, T.-T.; Ng, S.-C. Chemically bonded cationic β-cyclodextrin derivatives and their applications in supercritical fluid chromatography. J. Chromatogr. A. 2012, 1224, 97103. https://doi.org/10.1016/j.chroma.2011.12.053.

    • Search Google Scholar
    • Export Citation
  • 75.

    Williams, K. L.; Sander, L. C.; Wise, S. A. Comparison of liquid and supercritical fluid chromatography using naphthylethylcarbamoylated-β-cyclodextrin chiral stationary phases. J. Chromatogr. A. 1996, 746, 91101. https://doi.org/10.1016/0021-9673(96)00291-9.

    • Search Google Scholar
    • Export Citation
  • 76.

    Folprechtová, D.; Kalíková, K. Macrocyclic glycopeptide-based chiral selectors for enantioseparation in sub/supercritical fluid chromatography. Anal. Sci. Adv. 2020, 2, 1532. https://doi.org/10.1002/ansa.202000099.

    • Search Google Scholar
    • Export Citation
  • 77.

    Phinney, K. W.; Sander, L. C. Preliminary evaluation of a standard reference material for chiral stationary phases used in liquid and supercritical fluid chromatography. Anal. Bioanal. Chem. 2002, 372, 101108. https://doi.org/10.1007/s00216-001-1198-2.

    • Search Google Scholar
    • Export Citation
  • 78.

    Phinney, K. W.; Sander, L. C. Additive concentration effects on enantioselective separations in supercritical fluid chromatography. Chirality 2003, 15, 287294. https://doi.org/10.1002/chir.10196.

    • Search Google Scholar
    • Export Citation
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Senior editors

Editor(s)-in-Chief: Kowalska, Teresa (1946-2023)

Editor(s)-in-Chief: Sajewicz, Mieczyslaw

Editors(s)

  • Danica Agbaba (University of Belgrade, Belgrade, Serbia)
  • Łukasz Komsta (Medical University of Lublin, Lublin, Poland)
  • Ivana Stanimirova-Daszykowska (University of Silesia, Katowice, Poland)
  • Monika Waksmundzka-Hajnos (Medical University of Lublin, Lublin, Poland)

Editorial Board

  • R. Bhushan (The Indian Institute of Technology, Roorkee, India)
  • J. Bojarski (Jagiellonian University, Kraków, Poland)
  • B. Chankvetadze (State University of Tbilisi, Tbilisi, Georgia)
  • M. Daszykowski (University of Silesia, Katowice, Poland)
  • T.H. Dzido (Medical University of Lublin, Lublin, Poland)
  • A. Felinger (University of Pécs, Pécs, Hungary)
  • K. Glowniak (Medical University of Lublin, Lublin, Poland)
  • B. Glód (Siedlce University of Natural Sciences and Humanities, Siedlce, Poland)
  • A. Gumieniczek (Medical University of Lublin, Lublin, Poland)
  • U. Hubicka (Jagiellonian University, Kraków, Poland)
  • K. Kaczmarski (Rzeszow University of Technology, Rzeszów, Poland)
  • H. Kalász (Semmelweis University, Budapest, Hungary)
  • K. Karljiković Rajić (University of Belgrade, Belgrade, Serbia)
  • I. Klebovich (Semmelweis University, Budapest, Hungary)
  • A. Koch (Private Pharmacy, Hamburg, Germany)
  • P. Kus (Univerity of Silesia, Katowice, Poland)
  • D. Mangelings (Free University of Brussels, Brussels, Belgium)
  • E. Mincsovics (Corvinus University of Budapest, Budapest, Hungary)
  • Á. M. Móricz (Centre for Agricultural Research, Budapest, Hungary)
  • G. Morlock (Giessen University, Giessen, Germany)
  • A. Petruczynik (Medical University of Lublin, Lublin, Poland)
  • R. Skibiński (Medical University of Lublin, Lublin, Poland)
  • B. Spangenberg (Offenburg University of Applied Sciences, Germany)
  • T. Tuzimski (Medical University of Lublin, Lublin, Poland)
  • Y. Vander Heyden (Free University of Brussels, Brussels, Belgium)
  • A. Voelkel (Poznań University of Technology, Poznań, Poland)
  • B. Walczak (University of Silesia, Katowice, Poland)
  • W. Wasiak (Adam Mickiewicz University, Poznań, Poland)
  • I.G. Zenkevich (St. Petersburg State University, St. Petersburg, Russian Federation)

 

KOWALSKA, TERESA (1946-2023)
E-mail: kowalska@us.edu.pl

SAJEWICZ, MIECZYSLAW
E-mail:msajewic@us.edu.pl

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2022  
Web of Science  
Total Cites
WoS
647
Journal Impact Factor 1.9
Rank by Impact Factor

Chemistry, Analytical (Q3)

Impact Factor
without
Journal Self Cites
1.9
5 Year
Impact Factor
1.4
Journal Citation Indicator 0.41
Rank by Journal Citation Indicator

Chemistry, Analytical (Q3)

Scimago  
Scimago
H-index
29
Scimago
Journal Rank
0.28
Scimago Quartile Score

Chemistry (miscellaneous) (Q3)

Scopus  
Scopus
Cite Score
3.1
Scopus
CIte Score Rank
General Chemistry 211/407 (48th PCTL)
Scopus
SNIP
0.549

2021  
Web of Science  
Total Cites
WoS
652
Journal Impact Factor 2,011
Rank by Impact Factor Chemistry, Analytical 66/87
Impact Factor
without
Journal Self Cites
1,789
5 Year
Impact Factor
1,350
Journal Citation Indicator 0,40
Rank by Journal Citation Indicator Chemistry, Analytical 72/99
Scimago  
Scimago
H-index
29
Scimago
Journal Rank
0,27
Scimago Quartile Score Chemistry (miscellaneous) (Q3)
Scopus  
Scopus
Cite Score
2,8
Scopus
CIte Score Rank
General Chemistry 210/409 (Q3)
Scopus
SNIP
0,586

2020
 
Total Cites
650
WoS
Journal
Impact Factor
1,639
Rank by
Chemistry, Analytical 71/83 (Q4)
Impact Factor
 
Impact Factor
1,412
without
Journal Self Cites
5 Year
1,301
Impact Factor
Journal
0,34
Citation Indicator
 
Rank by Journal
Chemistry, Analytical 75/93 (Q4)
Citation Indicator
 
Citable
45
Items
Total
43
Articles
Total
2
Reviews
Scimago
28
H-index
Scimago
0,316
Journal Rank
Scimago
Chemistry (miscellaneous) Q3
Quartile Score
 
Scopus
393/181=2,2
Scite Score