Authors:
Ali Fouad Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Al-Azhar University, Assiut, 71524, Egypt

Search for other papers by Ali Fouad in
Current site
Google Scholar
PubMed
Close
https://orcid.org/0000-0003-4330-9932
,
Ahmed S. Abdelkhalek Department of Medicinal Chemistry, Faculty of Pharmacy, Zagazig University, Zagazig, 44519, Egypt

Search for other papers by Ahmed S. Abdelkhalek in
Current site
Google Scholar
PubMed
Close
,
Hisham Elrefay Simco Pharmaceutical Industries, 6th of October, Egypt

Search for other papers by Hisham Elrefay in
Current site
Google Scholar
PubMed
Close
,
Hany A. Batakoushy Department of Pharmaceutical Analytical Chemistry, Faculty of Pharmacy, Menoufia University, Shebin Elkom, 32511, Egypt

Search for other papers by Hany A. Batakoushy in
Current site
Google Scholar
PubMed
Close
https://orcid.org/0000-0002-9958-4290
, and
Moustafa K. Soltan Department of Medicinal Chemistry, Faculty of Pharmacy, Zagazig University, Zagazig, 44519, Egypt
Oman College of Health Sciences, Ministry of Health, Muscat, Sultanate of Oman

Search for other papers by Moustafa K. Soltan in
Current site
Google Scholar
PubMed
Close
Open access

Abstract

A simple, sensitive, selective, accurate and precise method was developed and fully validated for determination of oxcarbazepine (OXC) in presence of their preservatives and determination of oxcarbazepine (OXC) in human plasma. A reversed phase liquid chromatography (RP-HPLC) with UV detection techniques were applied for separation and quantification of studied drug OXC. Successful separation of the drug from methyl paraben (M.P.), propyl paraben (P.P.) and potassium sorbate (P.ST.) was achieved on a Kromasil C18 column (5 μm particle size, pore size 300 Å, l × I.D. 250 × 4.6 mm). The mobile phase that contain aqueous 0.05M potassium dihydrogen phosphate buffer (pH 7): acetonitrile, (50: 50, %v/v). The method was linear over concentration ranges 5.0–50 μg mL−1 for OXC. Bioanalytical validation of the developed method was carried out according to US-FDA guidelines and revealed a good linear relations over a range of (5.0–50), (0.5–10), (0.05–0.15), and (1.0–10) μg mL−1 for OXC, M.P, P.P, and P.ST, respectively, with a correlation coefficient (R2) of more than 0.999. Limit of detection (LOD) were 1.15, 0.03, 0.01 and 0.04 μg mL−1 for OXC, M.P, P.P, and P.ST, respectively, Intra and inter-day precisions, calculated as percentage relative standard deviation (% RSD), were lower than 2.0%. The developed method can be applied for routine drug analysis, therapeutic drug monitoring and bioequivalence studies through the analysis of plasma samples taken from blood bank.

Abstract

A simple, sensitive, selective, accurate and precise method was developed and fully validated for determination of oxcarbazepine (OXC) in presence of their preservatives and determination of oxcarbazepine (OXC) in human plasma. A reversed phase liquid chromatography (RP-HPLC) with UV detection techniques were applied for separation and quantification of studied drug OXC. Successful separation of the drug from methyl paraben (M.P.), propyl paraben (P.P.) and potassium sorbate (P.ST.) was achieved on a Kromasil C18 column (5 μm particle size, pore size 300 Å, l × I.D. 250 × 4.6 mm). The mobile phase that contain aqueous 0.05M potassium dihydrogen phosphate buffer (pH 7): acetonitrile, (50: 50, %v/v). The method was linear over concentration ranges 5.0–50 μg mL−1 for OXC. Bioanalytical validation of the developed method was carried out according to US-FDA guidelines and revealed a good linear relations over a range of (5.0–50), (0.5–10), (0.05–0.15), and (1.0–10) μg mL−1 for OXC, M.P, P.P, and P.ST, respectively, with a correlation coefficient (R2) of more than 0.999. Limit of detection (LOD) were 1.15, 0.03, 0.01 and 0.04 μg mL−1 for OXC, M.P, P.P, and P.ST, respectively, Intra and inter-day precisions, calculated as percentage relative standard deviation (% RSD), were lower than 2.0%. The developed method can be applied for routine drug analysis, therapeutic drug monitoring and bioequivalence studies through the analysis of plasma samples taken from blood bank.

1 Introduction

Oxcarbazepine (OXC) [1] is a carbamazepine keto analogue, Fig. 1. OXC is antiepileptic drug that has been approved for treatment of partial seizures and trigeminal neuralgia in the United States and the European Union as well as more than 50 countries worldwide. OXC is less toxic and has a more favorable pharmacokinetic profile than carbamazepine [2]. It has a good oral bioavailability and rapidly metabolized to form the pharmacologically active 10-monohydroxy derivative [2]. Pharmaceutical preparations, syrups and suspensions, contain an aqueous vehicle which may affect product stability or could be infectious to patient, thus requires safeguards from microbial contamination [3]. Addition of anti-microbial agents to formulation is required to inhibit the growth of microorganisms during drug manufacture and use [4]. Preservatives are effective to control mold and yeast growth including limited agents as p-hydroxybenzoic acid esters: methyl paraben (M.P.) C6H4 (OH) COOCH3, propyl paraben (P.P.) C6H4 (OH) COOC3H7 and potassium sorbate (P.ST.) C6H7KO2, Fig. 1 [1]. These preservatives characterized by their broad antimicrobial spectrum, good stability and non-volatility [5]. A synergetic effect obtained when both M.P. and P.P are used in combination [6].

Fig. 1.
Fig. 1.

Chemical structure of oxcarbazepine(A), Methyl paraben (B), Propyl paraben (C), and potassium sorbate (D)

Citation: Acta Chromatographica 36, 3; 10.1556/1326.2023.01157

OXC was analyzed and validated in many of literature articles using different mobile phases, column and detector. (Supplementary data: Table S1). In 2019, quantification of OXC in tablets was carried out with stability indicating HPLC method (HPLC with photodiode array detector) [7]. Determination of OXC was conducted by M.L. Qi et al. in new pharmaceutical preparation [8]. A simple method to monitor plasma concentrations of oxcarbazepine, carbamazepine, their main metabolites and lamotrigine in epileptic patients [9]. Oxcarbazepine was also determined using UHPLC technique [10].

A three structurally related antiepileptic drugs; carbamazepine, OXC, eslicarbazepine acetate and their main metabolites (i.e. carbamazepine-10,11-epoxide, 10,11-trans-dihydroxy-10,11-dihydro carbamazepine, and licarbazepine) was validate using HPLC-UV detection method [11]. A high-performance liquid chromatographic determination of OXC and its active metabolite in human serum and plasma was also reported in the literature [12–16]. In 2019, oxcarbazepine was clinically quantified in human plasma using a nondestructive tool called Surfaced-Enhanced Raman Spectroscopy (SERS) combined with chemometrics analysis [17].

Methyl parapen, propyl parapen and potassium sorbate were determined using High Performance Liquid Chromatography LC–UV, LC–MS/MS, HPLC–UV, RPC and gradient RP-HPLC methods [18–22]. RP-HPLC method was assigned by Muhammad F. et al. for determination of methyl paraben sodium (MPS) and propyl paraben sodium iron protein succinylate syrup [23].

Parabens were determined in biological samples i.e. blood and urine using FPSE-HPLC-PDA techniques [24]. Up to date no validated analytical method for the determination of OXC, methyl paraben, propyl paraben and potassium sorbate in oral suspension formulation was available in literature. Here, RP-HPLC method was used because of its unique characters, as it is environmentally and economically benign than other methods [25–30]. Up to date in 2021 Kwabena F. et al. discussed common chromatographic principles, requirements and/or conditions for HPLC as applied to assay of oxacarbazepine and 27 antiepileptic drugs in six biological matrices [31].

Herein, a proposed method for accurate, selective, and reliable HPLC-UV method quantification of OXC and its preservatives in plasma was developed. The development of a single assay for the determination of the studied antiepileptic drug saved time and was cost effective, representing an advantage of this research.

2 Materials and methods

2.1 Reagents and chemicals

Oxcarbazepine OXC, methyl paraben (M.P.), propyl paraben (P.P.) and potassium sorbate (P.ST.) were obtained from Simco pharma (Egypt). Oxaleptal 60 mg mL−1® oral suspension was purchased from the Egypt market. Plasma samples were taken from Egyptian blood bank, Shebin Elkome Hospital (Egypt). Methanol (HPLC grade optained from Scharlau), KH2PO4 and sodium hydroxide were obtained from Panreac (USA), 0.45 μm Whatman filter were purchased from Sigma-Aldrich for syringe filter. Ultrapure water (Milli-Q) (Millipore Corporation, Billerica, MA, USA) was used.

2.2 Instrumentation and chromatographic conditions

2.2.1 HPLC-UV analyses

The HPLC system (Waters, USA) was equipped with auto sampler, Binary HPLC Pumps, Dual lamp Absorbance Detector and In-Line Degasser ISA Card. Data acquisition was performed on Empower software. The detector was set to 250 nm. The HPLC separation and quantitation were achieved on Kromasil C18 column (5 μm particle size, pore size 300 Å, l × I.D. 250 × 4.6 mm). All determinations were performed at 30 ºC. The mobile phase buffer solution was prepared by transferring accurately weighed about 6.8 g of Potassium dihydrogen phosphate into 1,000 mL volumetric flask. Add 500 mL purified water mixed to dissolve. The volume was completed by the same solvent. The Mobile phase composed of buffer: Acetonitrile (50: 50, %v/v) and pH adjusted to 7 with 1M NaOH, which was run Isocratic. Flow rate was 1.5 mL min−1 and injection volume was 20 μl. (Supplementary data: Table S2).

2.3 Preparation of standard solutions

(Solution A): To 33 mg of OXC working standard in 50 mL volumetric flask, 25 mL acetonitrile was added, stirred till complete dissolution then mobile phase was used to complete to the final volume. (Solution B): Transfer methyl paraben (19.8 mg) of working standard into volumetric flask (100 mL), add mobile phase to complete to a required volume and the mixture shake well to dissolve. (Solution C): 5 mL from solution B was transferred to volumetric flask (50 mL) then completed by mobile phase to required volume. (Solution D): Propyl paraben (22 mg) working standard transferred into volumetric flask (100 mL), then final volume obtained by mobile phase and shake well to dissolve. (Solution E): 1 mL from solution D was taken into 100 mL volumetric flask then completed to volume by mobile phase. (Solution F): 22 mg of potassium sorbate working standard was transferred into volumetric flask (100 mL), and then completed to volume by mobile phase and shake well to dissolve. (Solution G): 5 mL from solution F was transferred into volumetric flask (50 mL) then completed to volume by mobile phase.

Standard solution: 5 mL from each of solutions A, C, E and G was transferred into volumetric flask (100 mL) then completed to volume by mobile phase. (Conc. of OXC, methyl paraben, propyl paraben and potassium sorbate is 33, 0.99, 0.11 and 1.1 μg mL−1).

2.4 Preparation of sample solutions

Oxaleptal oral suspension (11 mL) was accurately measured and transferred to a volumetric flask (200 mL), added water (10 mL), stirred for 5 min; then acetonitrile (50 mL) was added, stirred for 30 min then the volume was completed by mobile phase.

1 mL was transferred from the previous solution into volumetric flask (100 mL), the volume was completed by mobile phase, mixed and centrifuged. (Conc. of OXC, methyl paraben, propyl paraben and potassium sorbate is 33, 0.99, 0.11 and 1.1 μg mL−1).

2.4.1 Forced degradation conditions

Acid degradation: the mixture of OXZ., M.P., P.P. and P.ST: was prepared as previously described in the preparation of working standard solution but 5 mL of 5M HCl was added to the analytes, shaking for 5 min and leaving for 1 h at room temperature, the mixture was neutralized by 5 mL of 5M NaOH before volumetric dilution with 100 mL.

Alkaline degradation: Prepared by adding 5 mL of 5M NaOH to the mixture of OXZ., M.P., P.P. and P.ST. standard solutions, containing equal amounts of working standard solutions, and shaking for 5 min. The solution was then kept at room temperature for 1 h and neutralized with 5 mL of 5M HCl. The volume was diluted to 100 mL using the mobile phase.

Oxidative degradation: prepared by adding 5 mL of 30% H2O2 to the same concentration of a mixture of OXZ. M.P., P.P. and P.ST: standard solution used in acid and alkaline degradation. A 5-min mixture shake was followed by 1 h of dark storage at room temperature, then 100 mL of the mobile phase was added.

Heating Hydrolysis of OXZ., M.P., P.P. and P.ST: To 11 gm of oxaleptal oral suspension in 100 mL volumetric flask, 10 mL of purified water and 50 mL methanol were added. They were shaken well for 30 min at 60 C° for 3 h in a water bath. As the flask cooled to room temperature, the mobile phase was mixed with the acquired volume and filtered. Transfer 5 mL into volumetric flask (50 mL) and add mobile phase to achieve desired volume, and then 5 mL was transferred into 100 mL flask and then completed to volume with Mobile phase.

Day light Hydrolysis of OXZ., M.P., P.P. and P.ST Suspension:

Carried out as mentioned in heat hydrolysis & put in day light for 6 h instead of heating.

2.5 Method validation

2.5.1 Accuracy

Accuracy estimated by applying of the proposed study to standard solution of OXC, M.P., P.P. and P.ST to which known quantities of analyte have been spiked within the range of the calibration curve. Accuracy should be assessed using at least three concentrations (80, 100 and 120%) with average recovery percent's ranging from 98% to 102% of spiked drug in plasma.

2.5.2 Precision

Precision of the proposed method is the degree of agreement among results of individual test when it applied repeatedly and it is expressed as the relative standard deviation RSD of a series of measurements. It should be assessed using at least six quantitation's at 100% of the test concentration. Obtained Relative Standard Deviation (RSD %) are within the accepted range (NMT 2%) indicating that the method is Precise and repeatable.

2.5.3 Linearity, LOD and LOQ

The linearity represents the ability to get results that are directly proportional to the concentration of drug in samples within specific range. A minimum of five concentrations should be used. If appears to be a linear relation, calculate regression coefficient and y-intercept which should be higher than 0.99 and near to zero respectively.

Linearity of the method represents its ability to get a direct relation between the obtained results and the given concentration of the drug. At the optimized HPLC conditions, linearity was obtained by injection of standard solution series of OXC, M.P., P.P. and P.ST at five different levels; 60, 80, 100, 120 and 140% of the selected concentration range. Plotting the peak area against the selected concentration was used estimate the calibration curves of each sample. The Slope (b), intercept (a) and correlation R2 were estimated. LOD was determined from the formula; LOD = 3.3 σ/SD, where (σ) is SD of the intercept and (S) is the slope of regression equation. LOQ was calculated similarly from the equation LOQ = 10 σ/S.

2.5.4 Robustness

The robustness of a method is its ability to be not affected by small variations in its parameters as temperature, wavelength, and change in mobile phase. This reproducibility under the normal parameters compared to the precision to get a measure of the robustness of the analytical method.

2.6 Application to human plasma samples

Into 10 mL centrifuge tube, serial working solutions were prepared then an accurate volume of 200 μl OXC, M.P., P.P. and P.ST standard solution was quantitatively added to 500 μl of blank plasma samples taken from Egyptian blood bank (Ethical Approval Number ZA-AS/PH/22/C/2023), then 2.0 mL acetonitrile were added as a protein precipitation, and vortex mixed for two minutes followed by centrifugation at 5,000 rpm for 20 min. Further supernatant filtration was done using membrane filter of cellulose acetate (0.45-m), then 20 µl was applied to the HPLC-UV system.

3 Results and discussion

3.1 Method development

Different mobile phase compositions and flow rates were investigated to determine the best optimum mobile phase for separation of OXC, M.P, P.P, and P.ST. It was discovered that separated peaks were obtained. As a result, the mobile phase was tested with four components to achieve the best resolution. Different ratios of acetonitrile and 0.05M KH2PO4 buffer were investigated. As shown in Fig. 2, phosphate buffer (0.05 M, pH 7): acetonitrile (50:50; % v/v) was optimal for separation.

Fig. 2.
Fig. 2.

2D chromatogram of the OXC (33 μg mL−1), M.P. (0.99 μg mL−1), P.P. (0.11 μg mL−1) and (P.ST.) (1.1 μg mL−1) using mobile phase of phosphate buffer (0.05 M, pH 7): acetonitrile (50:50; % v/v) and UV detection at 254 nm

Citation: Acta Chromatographica 36, 3; 10.1556/1326.2023.01157

The pH range of 0.05 M phosphate buffer was tested from 5.0 to 9.0 to ensure good separation of OXC, M.P, P.P, and P.ST. According to Fig. 3, pH 7 was optimal for separation.

Fig. 3.
Fig. 3.

Effect of pH range of 0.05 M phosphate buffer from 5.0 to 9.0 to ensure good separation of OXC, M.P, P.P, and P.ST. pH 7 was optimal for separation

Citation: Acta Chromatographica 36, 3; 10.1556/1326.2023.01157

Moreover, the effect of flow rate was investigated in order to achieve sharp symmetric peaks of the cited drug in a reasonable amount of time. Flow rates ranging from 1.0 to 2.0 mL min−1 were found to provide good separation between the OXC, M.P, P.P, and P.ST with sharp symmetric peaks, so 1.5 mL min−1 was determined to be the appropriate flow rate. (Supplementary data: Fig. S1) illustrated the comparison of OXC and placebo.

Despite the proposed method is simple, accurate and rapid, but it still has limitations include multiple steps need to be optimized and the run time need to be shorter or the separation need to be quicker.

3.2 Method validation

The HPLC method was validated using ICH [32] rules and bio analytically using US-FDA guidelines [33].

3.2.1 Accuracy, precision

The proposed approach's accuracy was assessed using % targeting concentrations of 80, 100, and 120%, and the percent recovery was (33, 0.99, 0.11, and 1.1 μg mL−1) by three times injection of each concentration on the HPLC-UV system for OXC, M.P., P.P., and P.ST. (Supplementary data: Table 1). Table 1 represents the conclusions, which show that the proposed method is highly accurate. The HPLC-UV method's high sensitivity ensures its suitability for tracing OXC and its preservative in oral suspension.

Table 1.

Accuracy of OXC and its preservatives in oxaleptal sample solution

% of targeting concentrationOXC

% recovery ± SD
M.P.

% recovery ± SD
P.P.

% recovery ± SD
P.ST.

% recovery ± SD
80%98.99 ± 0.06799.88 ± 0.1099.29 ± 1.19699.03 ± 0.444
100%99.88 ± 0.037101.01 ± 0.1299.47 ± 0.09799.28 ± 0.018
120%101.5 ± 0.061100.94 ± 0.1299.73 ± 0.23101.46 ± 0.086

SD: Standard deviation

US-FDA criteria was used to bioanalytical validate the explored approach, with the accuracy and precision tested in human plasma. OXC; three concentrations, were assessed intraday (n = 6) and interday (n = 9) using low quality control samples (LQC), medium quality control samples (MQC), and high-quality control samples (HQC). Table 2 shows that human plasma has good repeatability, with a percent RSD less than 2.0 and a percent recovery ranging from 96.88 to 97.77%.

Table 2.

Accuracy and precision of the proposed method for determination of studied drug in human plasma

Conc. taken (µg mL−1)Intra-day assay (n = 6)Inter-day assay (n = 9)
Accuracy (%Recovery)Precision (%RSD)Accuracy (%Recovery)Precision (%RSD)
OXC
1596.991.1996.881.18
2597.770.0697.540.12
3597.290.4497.730.08

3.2.2 Selectivity

Analysis of Oxaleptal oral suspension (60 mg mL−1) was confirmed selectivity of the proposed method. No interference with the target analytes was observed in presence of the excipients. The representative chromatogram of OXC, M.P., P.P. and P.ST in Oxaleptal oral suspension showed no interfering peaks from excipient components (Fig. 4).

Fig. 4.
Fig. 4.

2D chromatogram of the OXC (33 μg mL−1), M.P. (0.99 μg mL−1), P.P. (0.11 μg mL−1) and (P.ST.) (1.1 μg mL−1) in oxaleptal oral suspension using mobile phase of phosphate buffer (0.05 M, pH 7): acetonitrile (50:50; % v/v) and UV detection at 254 nm

Citation: Acta Chromatographica 36, 3; 10.1556/1326.2023.01157

3.2.3 Linearity, LOD and LOQ

The linearity concentration ranges for OXC, M.P, P.P, and P.ST were found to be (5.0–50), (0.5–10), (0.05–0.15), and (1.0–10) μg mL−1, respectively. The linearity range and the sensitive parameters were summarized (Supplementary data: Table 3). The calculated results, summarized in Table 3, indicate sensitive HPLC method as other reported methods [12–16].

Table 3.

Calibration parameters of 60, 80, 100, 120 and 140% of target concentrations of the linearity concentration ranges of OXC, M.P, P.P and P.ST is 33, 0.99, 0.11 and 1.1 μg mL−1)

AnalytesRange (µg mL−1)LOD (µg mL−1)LOQ (µg mL−1)SlopeIntercept ± SDr2
OXC5.0–501.153.47772179 ± 550.9995
M.P.0.5–100.030.1245112 ± 500.9994
P.P.0.05–0.150.010.04170313 ± 750.9994
P.ST.1.0–100.040.11457254 ± 650.9993

To investigate the matrix effect and selectivity in human plasma, three quality control samples (LQC, MQC, and HQC) (15, 25, and 35 μg mL−1) for OXC were used. The recovery percent range was between 96.25 ± 0.88 and 97.19 ± 1.25. The results' lack of plasma matrix effect confirms the technique's outstanding selectivity, as shown in Table S3.

3.2.4 Robustness

To evaluate the robustness of the suggested HPLC-UV technique, the impacts of minor deviations from ideal chromatographic parameters, such as (mobile phase system ratio, pH value, mobile phase flow rate, and detection wavelength), were studied. The performance of the developed technique was demonstrated to be unaffected by this minor change in the experimental settings, guaranteeing the method's reliability.

Based on FDA [33] recommendations, incurred sample reanalysis (ISR) was investigated as a parameter for bio-analytical validations to confirm the accuracy and precision of incurred samples. ISR is calculated as (% difference between initial and incurred samples/Mean) x 100. Based on the HPLC analysis, the percentage variation between samples ranged from 3.20 to 4.11%.The findings concern the suitability and sensitivity of the HPLC method for estimating OXC (Table S4).

3.2.5 Applications of HPLC in human plasma

The recovery percentage for the tested procedures at five different concentration levels was discovered to be between 95.12 and 98.24 percent, as shown in Table 4. The percent RSD value for the examined OXC was 0.83–1.12. These findings are consistent with other methods reported and fall within the acceptable range of analytical method variability due to different matrix effects.

Table 4.

Analysis of OXC and their preservatives in spiked human plasma using the proposed HPLC-UV method

OXC,

Conc (µg mL−1)
%Recovery* ± SDM.P,

Conc (µg mL−1)
%Recovery* ± SDP.P,

Conc (µg mL−1)
%Recovery* ± SDP.ST,

Conc (µg mL−1)
%Recovery* ± SD
5.098.24 ± 1.120.598.99 ± 0.110.0599.24 ± 1.161.099.32 ± 0.14
1096.33 ± 1.501.5100.05 ± 0.250.0699.67 ± 0.092.5101.63 ± 0.18
2095.12 ± 0.833.5101.14 ± 0.170.0798.83 ± 0.434.5102.16 ± 0.08
4097.20 ± 0.986.699.89 ± 0.330.09101.42 ± 0.176.599.48 ± 0.017
5095.88 ± 1.071099.64 ± 0.400.1597.86 ± 1.201098.66 ± 1.23

*Average of five replicates.

The purpose of this work was to create and validate an HPLC-UV technique for measuring OXC, M.P., P.P. and P.ST in plasma (Fig. 5). The design of a single assay for the determination of the examined antiepileptic drug and its preservatives saved time and cost, which was a value of this study. A validated analytical approach is required to produce data that allow for adequate patient monitoring during therapy. Furthermore, in a typical laboratory where a high number of samples must be tested on a routine basis, short analysis times, simple instrumentation, and simple chromatographic conditions are required. Thus, a speedy, simple, selective, accurate, exact, and sensitive HPLC-UV technique for determining OXC and its preservatives is presented here. The recommended HPLC method can be used to evaluate OXC for quality control.

Fig. 5.
Fig. 5.

2D chromatogram of the the OXC (33 μg mL−1), M.P. (0.99 μg mL−1), P.P. (0.11 μg mL−1) and (P.ST.) (1.1 μg mL−1) in spiked plasma using mobile phase of phosphate buffer (0.05 M, pH 7): acetonitrile (50:50; % v/v) and UV detection at 254 nm

Citation: Acta Chromatographica 36, 3; 10.1556/1326.2023.01157

3.2.6 Forced degradation studies

Samples of OXC, M.P., P.P. (and P.ST) standard solutions were subjected to forced degradation in NaOH, HCl, H2O2, heat, and light. The degradation samples were analyzed using the proposed method. Minor degradations of OXC, M.P., P.P. and P.ST were observed under acidic, oxidative, heat and light conditions at room temperature. At room temperature, OXC, M.P., P.P. and P.ST peaks showed approximately 20%, 11%, 11% and 14% degradation under the alkaline condition as shown in Fig. 6, respectively. All degradation products were chromatographically resolved from target analytes resolution between every two successive peaks was greater than 2.

Fig. 6.
Fig. 6.

2D chromatogram of the OXC (33 μg mL−1), M.P. (0.99 μg mL−1), P.P. (0.11 μg mL−1) and (P.ST.) (1.1 μg mL−1) in oxaleptal oral suspension after alkaline degradation using mobile phase of phosphate buffer (0.05 M, pH 7): acetonitrile (50:50; % v/v) and UV detection at 254 nm

Citation: Acta Chromatographica 36, 3; 10.1556/1326.2023.01157

4 Conclusions

A quick, accurate, and simple HPLC analytical method has been developed for the current study. For the routine analysis of OXC in oral suspension dosage form and spiked human plasma, this method was bio analytically validated. A reversed phase liquid chromatography (RP-HPLC) with UV detection techniques were applied for separation and quantification of studied drug OXC. Successful separation of the drug from methyl paraben (M.P.), propyl paraben (P.P.) and potassium sorbate (P.ST.) was achieved and bioanalytical validation of the developed method was carried out according to US-FDA guidelines and revealed a good linear relations over a range of (5.0–50), (0.5–10), (0.05–0.15), and (1.0–10) μg mL−1 for OXC, M.P, P.P, and P.ST, respectively. The developed method can be applied for routine drug analysis, therapeutic drug monitoring and bioequivalence studies through the analysis of plasma samples taken from blood bank. Further investigations are still in place to get more economically and environmentally benign methods for separation and quantification of studied drug OXC.

Ethics approval and consent to participate

The faculty of pharmacy, Al-Azhar University, Assuit Branch research ethical committee certifies that the research protocol presented by. Dr Ali Fouad, is compatible with the faculty scientific research ethic regulations, Dr Ali Fouad, was considered as preventative for all of the authors in the study.

Approval number ZA-AS/PH/22/C/2023.

Validity of approval 20/01/2023 to 19/01/2024.

Consent for publication

Not applicable.

Availability of data and materials

Not applicable.

Competing interests

The authors have declared no conflict of interest.

Funding

This article was self-funded.

Authors' contributions

Ali Fouad and Hany A. Batakoushy: research idea conceptualization; supervised the study; data analysis; manuscript writing, revision, and editing. Ahmed S. Abdelkhalek: Methodology, writing – original draft, data curation, validation, revision and editing. Hisham Elrefay: Methodology, writing – original draft and validation. Moustafa K. Soltan: Writing – review & editing.

Authors' information

Not applicable.

Acknowledgments

Not applicable.

Supplementary data

Supplementary data to this article can be found online at https://doi.org/10.1556/1326.2023.01157.

List of abbreviations

UHPLC

Ultra-High-Performance Liquid Chromatography

LC-MS-MS

Liquid Chromatography with tandem mass spectrometry

RPC

Remote procedure call

FPSE

Fabric phase sorptive extraction

References

  • 1.

    USP, T.U.S.P., 39th ed., United States Pharmacopoeial, R. Convention, MD, USA, 2016, pp. 5687e5694. Monograph for, and O.O.S. Oxcarbazepine, and Oxcarbazepine Tablets.

  • 2.

    Glauser, T. A. Oxcarbazepine in the treatment of epilepsy. Pharmacother. J. Hum. Pharmacol. Drug Ther. 2001, 21(8), 904919.

  • 3.

    Walsh, J.; Ranmal, S. R.; Ernest, T. B.; Liu, F. Patient acceptability, safety and access: a balancing act for selecting age-appropriate oral dosage forms for paediatric and geriatric populations. Int. J. Pharm. 2018, 536(2), 547562.

    • Search Google Scholar
    • Export Citation
  • 4.

    Mirsonbol, S. Z.; Issazadeh, K.; Pahlaviani, M. R. M. K.; Momeni, N. Antimicrobial efficacy of the methylparaben and benzoate sodium against selected standard microorganisms, clinical and environmental isolates in vitro. Vitro. Indian J. Fundam. Appl. Life Sci. 2014, 4(S4), 363367.

    • Search Google Scholar
    • Export Citation
  • 5.

    M Kashid, R.; Singh, S. G.; Singh, S. Simultaneous determination of preservatives (methyl paraben and propyl paraben) in sucralfate suspension using high performance liquid chromatography. E-Journal Chem. 2011, 8(1), 340346.

    • Search Google Scholar
    • Export Citation
  • 6.

    Saad, B.; Bari, M. F.; Saleh, M. I.; Ahmad, K; Talib, M. K. M. Simultaneous determination of preservatives (benzoic acid, sorbic acid, methylparaben and propylparaben) in foodstuffs using high-performance liquid chromatography. J. Chromatogr. A 2005, 1073(1–2), 393397.

    • Search Google Scholar
    • Export Citation
  • 7.

    Pradhan, D. P.; Annapurna, M. M. Stability indicating HPLC-DAD method for the determination of Oxcarbazepine-An Anticonvulsant. Res. J. Pharm. Technol. 2019, 12(2), 723728.

    • Search Google Scholar
    • Export Citation
  • 8.

    Qi, M.; Wang, P.; Wang, L. J.; Fu, R. N. LC method for the determination of oxcarbazepine in pharmaceutical preparations. J. Pharm. Biomed. Anal. 2003, 31(1), 5762.

    • Search Google Scholar
    • Export Citation
  • 9.

    Franceschi, L.; Furlanut, M. A simple method to monitor plasma concentrations of oxcarbazepine, carbamazepine, their main metabolites and lamotrigine in epileptic patients. Pharmacol. Res. 2005, 51(4), 297302.

    • Search Google Scholar
    • Export Citation
  • 10.

    Žirojević, J.; Drljevic-Đurić, K.; Đurđević, A. Determination of oxcarbazepine and its related substances using UHPLC method with UV detection. Arh Farm 2014, 64, 8394.

    • Search Google Scholar
    • Export Citation
  • 11.

    Fortuna, A.; Sousa, J.; Alves, G.; Falcão, A.; Soares-da-Silva, P. Development and validation of an HPLC-UV method for the simultaneous quantification of carbamazepine, oxcarbazepine, eslicarbazepine acetate and their main metabolites in human plasma. Anal. Bioanal. Chem. 2010, 397(4), 16051615.

    • Search Google Scholar
    • Export Citation
  • 12.

    Breton, H.; Cociglio, M.; Bressolle, F.; Peyriere, H.; Blayac, J. P.; Hillaire-Buys, D. Liquid chromatography–electrospray mass spectrometry determination of carbamazepine, oxcarbazepine and eight of their metabolites in human plasma. J. Chromatogr. B 2005, 828(1–2), 8090.

    • Search Google Scholar
    • Export Citation
  • 13.

    Menge, G.; Dubois, J. Determination of oxcarbazepine in human plasma by high-performance liquid chromatography. J. Chromatogr. B: Biomed. Sci. Appl. 1983, 275, 189194.

    • Search Google Scholar
    • Export Citation
  • 14.

    Rouan, M. Automated microanalysis of oxcarbazepine and its monohydroxy and transdiol metabolites in plasma by liquid chromatography. J. Chromatogr. B: Biomed. Sci. Appl. 1994, 658(1), 167172.

    • Search Google Scholar
    • Export Citation
  • 15.

    Levert, H.; Odou, P.; Robert, H. LC determination of oxcarbazepine and its active metabolite in human serum. J. Pharm. Biomed. Anal. 2002, 28(3-4), 517525.

    • Search Google Scholar
    • Export Citation
  • 16.

    Mandrioli, R.; Ghedini, N.; Albani, F.; Kenndler, E.; Raggi, M. A. Liquid chromatographic determination of oxcarbazepine and its metabolites in plasma of epileptic patients after solid-phase extraction. J. Chromatogr. B 2003, 783(1), 253263.

    • Search Google Scholar
    • Export Citation
  • 17.

    Liu, M.; Wang, Y.; Jiang, Y.; Liu, H.; Chen, J.; Liu, S. Quantitation of oxcarbazepine clinically in plasma using surfaced-enhanced Raman spectroscopy (SERS) coupled with chemometrics. Appl. Spectrosc. 2019, 73(7), 801809.

    • Search Google Scholar
    • Export Citation
  • 18.

    Pylypiw, H. M., Jr; Grether, M. T. Rapid high-performance liquid chromatography method for the analysis of sodium benzoate and potassium sorbate in foods. J. Chromatogr. A 2000, 883(1-2), 299304.

    • Search Google Scholar
    • Export Citation
  • 19.

    Gören, A. C.; Bilsel, G.; Şimşek, A.; Bilsel, M.; Akçadağ, F.; Topal, K.; Ozgen, H. HPLC and LC–MS/MS methods for determination of sodium benzoate and potassium sorbate in food and beverages: performances of local accredited laboratories via proficiency tests in Turkey. Food Chem. 2015, 175, 273279.

    • Search Google Scholar
    • Export Citation
  • 20.

    Kreuz, D. M.; Howard, A. L.; Ip, D. Determination of indinavir, potassium sorbate, methylparaben, and propylparaben in aqueous pediatric suspensions. J. Pharm. Biomed. Anal. 1999, 19(5), 725735.

    • Search Google Scholar
    • Export Citation
  • 21.

    Can, N. O.; Arli, G.; Lafci, Y. A novel RP‐HPLC method for simultaneous determination of potassium sorbate and sodium benzoate in soft drinks using C18‐bonded monolithic silica column. J. Separat. Sci. 2011, 34(16–17), 22142222.

    • Search Google Scholar
    • Export Citation
  • 22.

    Byrne, J.; Velasco-Torrijos, T.; Reinhardt, R. Development and validation of a novel stability-indicating HPLC method for the simultaneous assay of betamethasone-17-valerate, fusidic acid, potassium sorbate, methylparaben and propylparaben in a topical cream preparation. J. Pharm. Biomed. Anal. 2014, 96, 111117.

    • Search Google Scholar
    • Export Citation
  • 23.

    Javed, M. F.; Zahra, M.; Javed, I.; Ahmad, S.; Jabeen, T.; Ahmad, M. Development and validation of RP HPLC method for the estimation of methyl paraben sodium and propyl paraben sodium in iron protein succinylate syrup. Acta Chromatographica 2023, 35(1), 5259.

    • Search Google Scholar
    • Export Citation
  • 24.

    Tartaglia, A.; Kabir, A.; Ulusoy, S.; Sperandio, E.; Piccolantonio, S.; Ulusoy, H. I.; Locatelli, M. FPSE-HPLC-PDA analysis of seven paraben residues in human whole blood, plasma, and urine. J. Chromatogr. B 2019, 1125, 121707.

    • Search Google Scholar
    • Export Citation
  • 25.

    Elrefay, H.; Ismaiel, O.; Hassan, W. S.; Shalaby, A.; Fouad, A. Simultaneous determination of levetiracetam and preservatives in oral solution formulation using HPLC-Uv method with a programble detection wavelength. Eurasian J. Anal. Chem. 2019, 14(4), 2531.

    • Search Google Scholar
    • Export Citation
  • 26.

    Elrefay, H. A.; Ismaiel, O. S.; Hassan, W.; Shalaby, A.; Fouad, A. A validated rapid reversed-phase high performance liquid chromatographic method for determination of risperidone and benzoic acid. Eurasian J. Anal. Chem. 2020, 15(1).

    • Search Google Scholar
    • Export Citation
  • 27.

    El-Adl, S. M.; El-Shanawany, A. A.; Abdel-Aziz, L. M.; Hassan, A. F. HPLC determination of three cephalosporins (cefepime, cefotriaxone and cefotaxime) in their bulk and dosage forms. Asian J. Pharm. Anal. 2014, 4(3), 9197.

    • Search Google Scholar
    • Export Citation
  • 28.

    Elrefay, H.; Ismaiel, O. A; Hassan, W. S.; Shalaby, A.; Fouad, A. RP-HPLC stability-indicating method for simultaneous determination of sodium valproate, methylparaben and propylparaben in oral solution. Acta Chromatographica 2021, 34(2), 203209.

    • Search Google Scholar
    • Export Citation
  • 29.

    Elrefay, H.; Ismaiel, O. A.; Hassan, W. S.; Shalaby, A.; Fouad, A.; Sebaiy, M. M. Mini-review on various analytical methods for determination of certain preservatives in different matrices. Int. J. Res. Stud. Sci. Eng. Technol.(IJRSSET) 2021, 8(2), 18.

    • Search Google Scholar
    • Export Citation
  • 30.

    El-Abasawy, N. M.; Sharaf El-din, M. M.; EL-Olemy, A.; Fouad, A. Determination of alogliptin benzoate and pioglitazone hydrochloride in their dosage forms, validation and stability-indicating studies using RP-HPLC method. Octahedron Drug Res. 2023, 2(1), 110.

    • Search Google Scholar
    • Export Citation
  • 31.

    Opuni, K. F.; Boadu, J. A.; Amponsah, S. K.; Okai, C. A. High performance liquid chromatography: a versatile tool for assaying antiepileptic drugs in biological matrices. J. Chromatogr. B 2021, 1179, 122750.

    • Search Google Scholar
    • Export Citation
  • 32.

    Guideline, I. Q2 (R1). Validation Anal. Procedures: Text Methodol. 2005, 541.

  • 33.

    Zimmer, D. New US FDA draft guidance on bioanalytical method validation versus current FDA and EMA guidelines: chromatographic methods and ISR. Bioanalysis 2014, 6(1), 1319.

    • Search Google Scholar
    • Export Citation

Supplementary Materials

  • 1.

    USP, T.U.S.P., 39th ed., United States Pharmacopoeial, R. Convention, MD, USA, 2016, pp. 5687e5694. Monograph for, and O.O.S. Oxcarbazepine, and Oxcarbazepine Tablets.

  • 2.

    Glauser, T. A. Oxcarbazepine in the treatment of epilepsy. Pharmacother. J. Hum. Pharmacol. Drug Ther. 2001, 21(8), 904919.

  • 3.

    Walsh, J.; Ranmal, S. R.; Ernest, T. B.; Liu, F. Patient acceptability, safety and access: a balancing act for selecting age-appropriate oral dosage forms for paediatric and geriatric populations. Int. J. Pharm. 2018, 536(2), 547562.

    • Search Google Scholar
    • Export Citation
  • 4.

    Mirsonbol, S. Z.; Issazadeh, K.; Pahlaviani, M. R. M. K.; Momeni, N. Antimicrobial efficacy of the methylparaben and benzoate sodium against selected standard microorganisms, clinical and environmental isolates in vitro. Vitro. Indian J. Fundam. Appl. Life Sci. 2014, 4(S4), 363367.

    • Search Google Scholar
    • Export Citation
  • 5.

    M Kashid, R.; Singh, S. G.; Singh, S. Simultaneous determination of preservatives (methyl paraben and propyl paraben) in sucralfate suspension using high performance liquid chromatography. E-Journal Chem. 2011, 8(1), 340346.

    • Search Google Scholar
    • Export Citation
  • 6.

    Saad, B.; Bari, M. F.; Saleh, M. I.; Ahmad, K; Talib, M. K. M. Simultaneous determination of preservatives (benzoic acid, sorbic acid, methylparaben and propylparaben) in foodstuffs using high-performance liquid chromatography. J. Chromatogr. A 2005, 1073(1–2), 393397.

    • Search Google Scholar
    • Export Citation
  • 7.

    Pradhan, D. P.; Annapurna, M. M. Stability indicating HPLC-DAD method for the determination of Oxcarbazepine-An Anticonvulsant. Res. J. Pharm. Technol. 2019, 12(2), 723728.

    • Search Google Scholar
    • Export Citation
  • 8.

    Qi, M.; Wang, P.; Wang, L. J.; Fu, R. N. LC method for the determination of oxcarbazepine in pharmaceutical preparations. J. Pharm. Biomed. Anal. 2003, 31(1), 5762.

    • Search Google Scholar
    • Export Citation
  • 9.

    Franceschi, L.; Furlanut, M. A simple method to monitor plasma concentrations of oxcarbazepine, carbamazepine, their main metabolites and lamotrigine in epileptic patients. Pharmacol. Res. 2005, 51(4), 297302.

    • Search Google Scholar
    • Export Citation
  • 10.

    Žirojević, J.; Drljevic-Đurić, K.; Đurđević, A. Determination of oxcarbazepine and its related substances using UHPLC method with UV detection. Arh Farm 2014, 64, 8394.

    • Search Google Scholar
    • Export Citation
  • 11.

    Fortuna, A.; Sousa, J.; Alves, G.; Falcão, A.; Soares-da-Silva, P. Development and validation of an HPLC-UV method for the simultaneous quantification of carbamazepine, oxcarbazepine, eslicarbazepine acetate and their main metabolites in human plasma. Anal. Bioanal. Chem. 2010, 397(4), 16051615.

    • Search Google Scholar
    • Export Citation
  • 12.

    Breton, H.; Cociglio, M.; Bressolle, F.; Peyriere, H.; Blayac, J. P.; Hillaire-Buys, D. Liquid chromatography–electrospray mass spectrometry determination of carbamazepine, oxcarbazepine and eight of their metabolites in human plasma. J. Chromatogr. B 2005, 828(1–2), 8090.

    • Search Google Scholar
    • Export Citation
  • 13.

    Menge, G.; Dubois, J. Determination of oxcarbazepine in human plasma by high-performance liquid chromatography. J. Chromatogr. B: Biomed. Sci. Appl. 1983, 275, 189194.

    • Search Google Scholar
    • Export Citation
  • 14.

    Rouan, M. Automated microanalysis of oxcarbazepine and its monohydroxy and transdiol metabolites in plasma by liquid chromatography. J. Chromatogr. B: Biomed. Sci. Appl. 1994, 658(1), 167172.

    • Search Google Scholar
    • Export Citation
  • 15.

    Levert, H.; Odou, P.; Robert, H. LC determination of oxcarbazepine and its active metabolite in human serum. J. Pharm. Biomed. Anal. 2002, 28(3-4), 517525.

    • Search Google Scholar
    • Export Citation
  • 16.

    Mandrioli, R.; Ghedini, N.; Albani, F.; Kenndler, E.; Raggi, M. A. Liquid chromatographic determination of oxcarbazepine and its metabolites in plasma of epileptic patients after solid-phase extraction. J. Chromatogr. B 2003, 783(1), 253263.

    • Search Google Scholar
    • Export Citation
  • 17.

    Liu, M.; Wang, Y.; Jiang, Y.; Liu, H.; Chen, J.; Liu, S. Quantitation of oxcarbazepine clinically in plasma using surfaced-enhanced Raman spectroscopy (SERS) coupled with chemometrics. Appl. Spectrosc. 2019, 73(7), 801809.

    • Search Google Scholar
    • Export Citation
  • 18.

    Pylypiw, H. M., Jr; Grether, M. T. Rapid high-performance liquid chromatography method for the analysis of sodium benzoate and potassium sorbate in foods. J. Chromatogr. A 2000, 883(1-2), 299304.

    • Search Google Scholar
    • Export Citation
  • 19.

    Gören, A. C.; Bilsel, G.; Şimşek, A.; Bilsel, M.; Akçadağ, F.; Topal, K.; Ozgen, H. HPLC and LC–MS/MS methods for determination of sodium benzoate and potassium sorbate in food and beverages: performances of local accredited laboratories via proficiency tests in Turkey. Food Chem. 2015, 175, 273279.

    • Search Google Scholar
    • Export Citation
  • 20.

    Kreuz, D. M.; Howard, A. L.; Ip, D. Determination of indinavir, potassium sorbate, methylparaben, and propylparaben in aqueous pediatric suspensions. J. Pharm. Biomed. Anal. 1999, 19(5), 725735.

    • Search Google Scholar
    • Export Citation
  • 21.

    Can, N. O.; Arli, G.; Lafci, Y. A novel RP‐HPLC method for simultaneous determination of potassium sorbate and sodium benzoate in soft drinks using C18‐bonded monolithic silica column. J. Separat. Sci. 2011, 34(16–17), 22142222.

    • Search Google Scholar
    • Export Citation
  • 22.

    Byrne, J.; Velasco-Torrijos, T.; Reinhardt, R. Development and validation of a novel stability-indicating HPLC method for the simultaneous assay of betamethasone-17-valerate, fusidic acid, potassium sorbate, methylparaben and propylparaben in a topical cream preparation. J. Pharm. Biomed. Anal. 2014, 96, 111117.

    • Search Google Scholar
    • Export Citation
  • 23.

    Javed, M. F.; Zahra, M.; Javed, I.; Ahmad, S.; Jabeen, T.; Ahmad, M. Development and validation of RP HPLC method for the estimation of methyl paraben sodium and propyl paraben sodium in iron protein succinylate syrup. Acta Chromatographica 2023, 35(1), 5259.

    • Search Google Scholar
    • Export Citation
  • 24.

    Tartaglia, A.; Kabir, A.; Ulusoy, S.; Sperandio, E.; Piccolantonio, S.; Ulusoy, H. I.; Locatelli, M. FPSE-HPLC-PDA analysis of seven paraben residues in human whole blood, plasma, and urine. J. Chromatogr. B 2019, 1125, 121707.

    • Search Google Scholar
    • Export Citation
  • 25.

    Elrefay, H.; Ismaiel, O.; Hassan, W. S.; Shalaby, A.; Fouad, A. Simultaneous determination of levetiracetam and preservatives in oral solution formulation using HPLC-Uv method with a programble detection wavelength. Eurasian J. Anal. Chem. 2019, 14(4), 2531.

    • Search Google Scholar
    • Export Citation
  • 26.

    Elrefay, H. A.; Ismaiel, O. S.; Hassan, W.; Shalaby, A.; Fouad, A. A validated rapid reversed-phase high performance liquid chromatographic method for determination of risperidone and benzoic acid. Eurasian J. Anal. Chem. 2020, 15(1).

    • Search Google Scholar
    • Export Citation
  • 27.

    El-Adl, S. M.; El-Shanawany, A. A.; Abdel-Aziz, L. M.; Hassan, A. F. HPLC determination of three cephalosporins (cefepime, cefotriaxone and cefotaxime) in their bulk and dosage forms. Asian J. Pharm. Anal. 2014, 4(3), 9197.

    • Search Google Scholar
    • Export Citation
  • 28.

    Elrefay, H.; Ismaiel, O. A; Hassan, W. S.; Shalaby, A.; Fouad, A. RP-HPLC stability-indicating method for simultaneous determination of sodium valproate, methylparaben and propylparaben in oral solution. Acta Chromatographica 2021, 34(2), 203209.

    • Search Google Scholar
    • Export Citation
  • 29.

    Elrefay, H.; Ismaiel, O. A.; Hassan, W. S.; Shalaby, A.; Fouad, A.; Sebaiy, M. M. Mini-review on various analytical methods for determination of certain preservatives in different matrices. Int. J. Res. Stud. Sci. Eng. Technol.(IJRSSET) 2021, 8(2), 18.

    • Search Google Scholar
    • Export Citation
  • 30.

    El-Abasawy, N. M.; Sharaf El-din, M. M.; EL-Olemy, A.; Fouad, A. Determination of alogliptin benzoate and pioglitazone hydrochloride in their dosage forms, validation and stability-indicating studies using RP-HPLC method. Octahedron Drug Res. 2023, 2(1), 110.

    • Search Google Scholar
    • Export Citation
  • 31.

    Opuni, K. F.; Boadu, J. A.; Amponsah, S. K.; Okai, C. A. High performance liquid chromatography: a versatile tool for assaying antiepileptic drugs in biological matrices. J. Chromatogr. B 2021, 1179, 122750.

    • Search Google Scholar
    • Export Citation
  • 32.

    Guideline, I. Q2 (R1). Validation Anal. Procedures: Text Methodol. 2005, 541.

  • 33.

    Zimmer, D. New US FDA draft guidance on bioanalytical method validation versus current FDA and EMA guidelines: chromatographic methods and ISR. Bioanalysis 2014, 6(1), 1319.

    • Search Google Scholar
    • Export Citation
  • Collapse
  • Expand

Senior editors

Editor(s)-in-Chief: Sajewicz, Mieczyslaw, University of Silesia, Katowice, Poland

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

  • Ravi Bhushan, The Indian Institute of Technology, Roorkee, India
  • Jacek Bojarski, Jagiellonian University, Kraków, Poland
  • Bezhan Chankvetadze, State University of Tbilisi, Tbilisi, Georgia
  • Michał Daszykowski, University of Silesia, Katowice, Poland
  • Tadeusz H. Dzido, Medical University of Lublin, Lublin, Poland
  • Attila Felinger, University of Pécs, Pécs, Hungary
  • Kazimierz Glowniak, Medical University of Lublin, Lublin, Poland
  • Bronisław Glód, Siedlce University of Natural Sciences and Humanities, Siedlce, Poland
  • Anna Gumieniczek, Medical University of Lublin, Lublin, Poland
  • Urszula Hubicka, Jagiellonian University, Kraków, Poland
  • Krzysztof Kaczmarski, Rzeszow University of Technology, Rzeszów, Poland
  • Huba Kalász, Semmelweis University, Budapest, Hungary
  • Katarina Karljiković Rajić, University of Belgrade, Belgrade, Serbia
  • Imre Klebovich, Semmelweis University, Budapest, Hungary
  • Angelika Koch, Private Pharmacy, Hamburg, Germany
  • Piotr Kus, Univerity of Silesia, Katowice, Poland
  • Debby Mangelings, Free University of Brussels, Brussels, Belgium
  • Emil Mincsovics, Corvinus University of Budapest, Budapest, Hungary
  • Ágnes M. Móricz, Centre for Agricultural Research, Budapest, Hungary
  • Gertrud Morlock, Giessen University, Giessen, Germany
  • Anna Petruczynik, Medical University of Lublin, Lublin, Poland
  • Robert Skibiński, Medical University of Lublin, Lublin, Poland
  • Bernd Spangenberg, Offenburg University of Applied Sciences, Germany
  • Tomasz Tuzimski, Medical University of Lublin, Lublin, Poland
  • Adam Voelkel, Poznań University of Technology, Poznań, Poland
  • Beata Walczak, University of Silesia, Katowice, Poland
  • Wiesław Wasiak, Adam Mickiewicz University, Poznań, Poland
  • Igor G. Zenkevich, St. Petersburg State University, St. Petersburg, Russian Federation

 

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

Indexing and Abstracting Services:

  • Science Citation Index
  • Sci Search
  • Research Alert
  • Chemistry Citation Index and Current Content/Physical
  • Chemical and Earth Sciences
  • SCOPUS
  • GoogleScholar
  • Index Copernicus
  • CABI
  • CABELLS Journalytics

2023  
Web of Science  
Journal Impact Factor 1.7
Rank by Impact Factor Q3 (Chemistry, Analytical)
Journal Citation Indicator 0.43
Scopus  
CiteScore 4.0
CiteScore rank Q2 (General Chemistry)
SNIP 0.706
Scimago  
SJR index 0.344
SJR Q rank Q3

Acta Chromatographica
Publication Model Online only
Gold Open Access
Submission Fee none
Article Processing Charge 400 EUR/article
Regional discounts on country of the funding agency World Bank Lower-middle-income economies: 50%
World Bank Low-income economies: 100%
Further Discounts Editorial Board / Advisory Board members: 50%
Corresponding authors, affiliated to an EISZ member institution subscribing to the journal package of Akadémiai Kiadó: 100%
Subscription Information Gold Open Access
Purchase per Title  

Acta Chromatographica
Language English
Size A4
Year of
Foundation
1988
Volumes
per Year
1
Issues
per Year
4
Founder Institute of Chemistry, University of Silesia
Founder's
Address
PL-40-007 Katowice, Poland, Bankowa 12
Publisher Akadémiai Kiadó
Publisher's
Address
H-1117 Budapest, Hungary 1516 Budapest, PO Box 245.
Responsible
Publisher
Chief Executive Officer, Akadémiai Kiadó
ISSN 2083-5736 (Online)

Monthly Content Usage

Abstract Views Full Text Views PDF Downloads
May 2024 0 71 31
Jun 2024 0 47 16
Jul 2024 0 114 43
Aug 2024 0 85 37
Sep 2024 0 86 40
Oct 2024 0 292 28
Nov 2024 0 31 10