A rapid high-performance liquid chromatography (HPLC) method for chiral purity determination of tenofovir disoproxil fumarate in raw material and pharmaceutical formulations was developed. The (S)-enantiomer appears to be as an impurity and pharmacologically inactive. The effects of various stationary phases, mobile phase composition, and column temperature on enantiomeric separation of tenofovir disoproxil were investigated and optimized. Chromatography resolution of tenofovir disoproxil enantiomers was performed on NUCLEOCEL ALPHA-RP S column (250 × 4.6 mm i.d., 5 μm). The elution was achieved by using 95:5% (υ/υ) methanol—acetonitrile, containing 0.1% triethylamine at a flow rate of 0.8 mL min−1. The ultraviolet (UV) detector was set at 260 nm. Calibration curves were linear in the range of 1–100 μg mL−1 and 0.2–20 μg mL−1 for (R)-tenofovir disoproxil and (S)-enantiomer, respectively. Limits of detection and quantitation for (S)-enantiomer were 0.06 and 0.2 μg mL−1. The run time of analysis was less than 7.0 min. The proposed method was used successfully for separation and quantification of tenofovir disoproxil enantiomers in raw material and pharmaceutical formulations.
The microextraction by packed sorbent (MEPS) was applied to a fractionation of cuticular wax extracts from several solanaceous plant species. A procedure developed requires only 0.6 mL of organic solvents and may be completed in less than 10 min. Hydrocarbons, which are frequently used in chemotaxonomy of Solanaceae, were almost exclusively eluted in one fraction. The amounts of most commonly detected polar wax components (alcohols, sterols, triterpenes) in the same fraction were reduced to ca. 34–46% of the total amounts in the whole extract. Despite the contamination of the hydrocarbon fraction with other wax components, the results obtained using MEPS and standard column chromatography on silica gel were similar when compared using cluster analysis based on the hydrocarbon profiles. However, the method was far less successful in removing the sucrose esters from extracts of Nicotiana rustica leaves. Thus, MEPS fractionation of plant cuticular waxes may be a fast and reliable alternative for the standard liquid chromatography techniques as long as no sucrose esters are present in the extract.
Authors:A. Pavlova, D. Stratiev, M. Mitkova, K. Stanulov, N. Dishovsky and K. Georgiev
Liquid products produced from two different types of waste pyrolysismunicipal wastes and spent tyre wastes are investigated using gas chromatography—mass spectrometry. This method has been applied for detailed identification of composition of the samples. The components were characterized in terms of their Kováts retention indices on a PONA capillary column. The obtained analytical data were successfully used for the characterization of the samples. More than three hundred compounds were detected. The liquid products were complex mixtures, composed mainly of C4—C12 compounds. The examination of the selected m/z values very clearly indicates the existence of the different groups of compounds. With a lot of olefins content (31.9%), followed by aromatics (20.0%), paraffins (17.3%), and naphthenes (7.5%), it is described as the liquid product from pyrolysis of municipal solid wastes. The aromatic compounds in liquid product from pyrolysis of spent tyre wastes have the highest concentration (33.5%), and they are followed by naphthenes (28.6%), olefins (19.2%), and paraffins compounds (7.0%). The present study has shown that the pyrolysis of municipal waste and spent tyres can be used as a means for reduction of environmental pollution and production of liquid product which could be used as a fuel source.
Authors:E.N. Fedorova, A.D. Kivero, N.V. Geraskina and L.R. Ptitsyn
A simple and rapid ultra-performance liquid chromatographic (UPLC) method for analyzing acetoin in bacterial culture fluid was developed and validated for the first time. The samples were separated using an Acquity BEH C18 column (2.1 mm × 100 mm, 1.7 μm particle size) and isocratic elution with 30 mM phosphoric acid—1% acetonitrile as the mobile phase. A photodiode array detector (PDA) was used. The run time was 6 min, and the detection limit was 2.11 × 10−4 mg mL−1. The UPLC method was compared with high-pressure liquid chromatography (HPLC) for acetoin analysis. The proposed UPLC method is highly sensitive and was successfully applied to the analysis of acetoin in bacterial culture fluid.
Authors:W. Kukula-Koch, J. Widelski, W. Koch and K. Głowniak
The presence of phenolic content in overground extracts of Euonymus verrucosus Scop. — commonly growing in Europe — has been reported recently. The chromatographical and spectral data revealed the presence of several simple phenolic acids (gallic, protocatechuic, p-hydroxybenzoic, vanillic, syringic, caffeic, p-coumaric, ferulic, and m-coumaric acids), both as free and conjugated with other secondary metabolites. The comparison of two-dimensional TLC systems on cellulose stationary phases with HPLC— DAD reversed-phase chromatography was performed to assess a cheap and rapid technique in the identification process of major phenolic constituents. 2,2-Diphenyl-1-picrylhydrazyl (DPPH) radical-scavenging tests, expressed as IC50, revealed the most beneficial results for the fraction after alkaline hydrolysis and yielded 205 ± 8 μg mL−1.
This work describes the comparison of five sample extraction methods for the determination of pesticide residues in grapes and vegetables by using gas chromatography—time-of-flight mass spectrometry (GC—TOF-MS). These methods were based on original methods QuEChERS, mini-Luke, ethyl acetate, and DIN EN 15637, and some of these were slightly modified to increase the number of identified and quantified pesticides, to improve their quantification limits, and to be fast and less expensive in terms of material cost. The acceptable performance parameters combined with the properties of easy and quick handling and cost-effectiveness have made mini-Luke modified extraction method as the most favorable in the pesticide residues analysis from grapes and tomatoes by GC—TOF-MS. The efficiency of the chosen extraction method was also verified for lettuce; for this matrix, a cleanup step with graphitized black carbon (GBC) was added. Analysis of extracts was carried out by GC—TOF-MS within 29.2 min run time. The GC method was validated for grapes and tomatoes in terms of linearity, accuracy, limit of detection (LOD), and limit of quantification (LOQ). Good linearity with correlation coefficients (r2) higher than 0.98 was obtained. For most analytes from both matrices, recoveries were in the range of 71–120% and LOQ values in the range of 0.01–0.05 mg kg−1. The GC—TOF-MS and modified mini-Luke extraction methods were successfully tested on real vegetable and fruit samples belonging to the same commodities group as those from validated methods according to European Guide DG SANCO 12571/2013 (tomatoes, pepper, cucumber, potatoes, carrots, eggplants, onion, lettuce and grapes) and in proficiency EU tests.
Authors:P.R. Ravi, S. Joseph, U. S. R. Avula and S. Anthireddy
The objective of this study was to develop and validate a novel, simple, and selective high-performance liquid chromatographic (HPLC) method with photodiode array detector for the estimation of tenofovir in rat plasma, which can be utilized in analyzing the pharmacokinetic samples from rats. Prior to analysis, an optimized protein precipitation technique was used to extract tenofovir from plasma. The mobile phase for this method comprised of 10 mM ammonium acetate buffer (pH 4) and methanol in the ratio of 97:3 υ/υ. Chromatographic separation of tenofovir was achieved using Spincotech C-18G enabled column (250 × 4.6 mm, 5 μm). Tenofovir was monitored at a wavelength of 260 nm, and the calibration curve was linear in the range of 250–4000 ng mL−1 (R2 = 0.999). High recovery obtained after extraction (97%–101%) of plasma samples precluded the use of an internal standard. Validation studies were performed as per the standard guidelines, and the developed method was accurate, precise, and selective for the determination of tenofovir in the rat plasma. The stability studies performed during the sample pretreatment process and sample storage conditions did not show a quantifiable degradation of tenofovir. Further, this method was able to estimate tenofovir and determine its pharmacokinetic parameters, post IV bolus administration in male Wistar rats. The pharmacokinetic profile of tenofovir followed one compartmental open model.
Authors:A. Kwiecień, K. Piątek, P. Żmudzki and J. Krzek
A simple, selective, and sensitive thin-layer chromatographic—densitometric method has been developed for the determination of sulfasalazine besides its possible impurities in pharmaceutical preparations. The mobile phase was composed of ethyl acetate—methanol—ammonia 25% 10:7:3 (υ/υ/υ), and the stationary phase was aluminum plates precoated with silica gel 60 F254 that enabled to obtain well resolved peaks of sulfasalazine and its impurities. The developed chromatograms were analyzed densitometrically at λ = 360 nm. RF values and ultraviolet (UV) spectra were used to identify the compounds. The developed method is highly sensitive (limit of detection [LOD] = 17.11 ng spot−1, limit of quantitation [LOQ] = 51.84 ng spot−1), precise (relative standard deviation [RSD] = 1.43%–4.28%), and accurate (RSD = 1.64%–4.27%). The linearity of the method was checked within the range 20–120 ng spot−1. The method was successfully applied for the determination of sulfasalazine in pharmaceutical preparations besides its impurities. The structures of impurities present in the standard substance and in pharmaceutical preparations were established by ultra-performance liquid chromatography—tandem mass spectrometry (UPLC—MS/MS) technique.
Authors:X. Wang, Y. Wu, Q. Wu, Y. Qian, W. Yue and Q. Liang
The rhizome of Sparganium stoloniferum Buch.-Ham has been used as a traditional Chinese folk medicine for thousands of years. Phenolic compounds are the main bioactive ingredients of the plant. In order to determine the content of phenolic compounds from different major cultivations, a reliable method has been developed using ultra-high performance liquid chromatography coupled with a triple quadrupole electrospray tandem mass spectrometry. Seven compounds, including rutin, kaempferol, p-hydroxybenzaldehyde, formononetin, ferulic acid, vanillic acid, and p-coumaric acid, were simultaneously measured in 10 min. The established approach was fully validated in terms of linearity, sensitivity, precision, repeatability as well as recovery, and successfully applied to determine seven phenolic compounds of Rhizoma Sparganii. This study may be helpful in the quality control of Rhizoma Sparganii and can offer technical support for the pharmacological and clinical study of related drugs.
Authors:S.T. Yang, X. Wu, W. Rui, J. Guo and Y.F. Feng
A rapid method has been used for simultaneous identification of both hydrophilic and lipophilic compounds from Radix Salviae Miltiorrhizae (RSM, the root of Salvia miltiorrhiza BGE.) by ultra-performance liquid chromatography/quadrupole time-offlight mass spectrometry (UPLC/Q-TOF-MS). A total of 58 compounds extracted by methanol were detected and tentatively identified within 20 min, including hydrophilic phenolics, lipophilic diterpenoids, a verbascose, and several organic acids. These compounds were separated on an Acquity UPLC BEH C18 column and identified based on tandem mass spectrometry (MS/MS) fragmentation patterns under the positive and negative ion modes, respectively. Among them, micranthin B and 9-oxo-10E,12Zoctadecadienoic acid were reported in RSM for the first time. Their fragmentation patterns in electrospray ionization (ESI)—MS/MS spectra were first investigated by matching their accurate molecular masses. This contribution presented one of the first reports on the analysis of hydrophilic phenolics and lipophilic diterpenoids from Radix Salviae Miltiorrhizae using UPLC/Q-TOF-MS. The results demonstrated that UPLC/Q-TOF-MS method could be applied to rapidly and expediently describe and provide comprehensive chemical information for simultaneous analysis of two different polar components in RSM.
Authors:J. Wang, M. Liu, X. Tong, W. Peng, H. Cao and W. Su
Shenqi Fuzheng Injection (SFI) is a traditional Chinese medicine injection, widely used to enhance immune function of clinical cancer patients undergoing chemotherapy. In this study, a high-performance liquid chromatography-diode array detection-evaporative light scattering detection (HPLC-DAD-ELSD) method was established for quality control of SFI, which could simultaneously semiquantitatively reflect the constituents displayed in the chromatographic profile of SFI. The relative retention time and relative peak areas of the 21 common peaks related to the reference peak were calculated. The validity and advantage of this method were validated by systematically comparing chromatograms of 10 batches of SFI samples with the analytical methods of principal component analysis and angle cosine method recommended by the State Food and Drug Administration of China. Moreover, a total of 21 constituents of SFI were identified or tentatively characterized in the fingerprint via ultrafast liquid chromatography-diode array detection-quadrupole time-of-flight (UFLC-DAD-Q-TOF) tandem mass spectrometry technique on the basis of the retention time, ultraviolet spectra, fragmentation patterns, and reported literatures. All the results proved that the technique was useful in comprehensive quality evaluation of SFI and further study.
Authors:R. P. Mangukiya, R. A. Patel, P. A. Shah and K. G. Patel
Two simple, accurate, specific, and precise chromatographic methods, reversed phase high-performance liquid chromatography (RP-HPLC) and highperformance thin-layer chromatography (HPTLC), have been developed and validated for the determination of moxifloxacin hydrochloride and difluprednate in ophthalmic dosage form according to International Conference on Harmonization (ICH) guidelines. The separation of moxifloxacin hydrochloride and difluprednate in HPLC was performed on reverse phase (C18, 5 μm, 250 × 4.6 mm) column using isocratic condition, with acetonitrile, 5 mM disodium hydrogen phosphate buffer adjusted to pH 5, and methanol (50:25:25, v/v/v) as mobile phase. The flow rate for analysis was 1.0 mL min−1, and the selected chromatographic conditions effectively separated moxifloxacin hydrochloride and difluprednate with retention time of 3.6 and 6.6 min, respectively, at a detection wavelength of 254 nm. Chromatographic development in HPTLC was performed on precoated silica gel 60F254 aluminium plates with n-hexane, 6 M ammonia, and acetone (5:1.8:2, v/v/v) as mobile phase. The detection wavelength for simultaneous estimation of both drugs was 232 nm in HPTLC, and the Rf values for moxifloxacin hydrochloride and difluprednate were 2.2 and 7.1, respectively. The linear concentration range for HPLC method was 5 to 50 μg mL−1 and 1 to 10 μg mL−1; and for HPTLC method was 1200 to 2200 ng band−1 and 200 to 1200 ng band−1 for moxifloxacin hydrochloride and difluprednate, respectively. Moreover, Bartlett's test applied on the calibration peak areas revealed homoscedasticity of variance for both the methods. Both methods were validated with respect to system suitability, specificity, linearity, precision, accuracy, and robustness. The mean percentage recoveries for marketed formulation in terms of accuracy were found to be 100.53 and 100.58 for HPLC; and 100.56 and 100.30 for HPTLC for moxifloxacin hydrochloride and difluprednate, respectively. The pooled percent relative standard deviation (% RSD) value for repeatability, intermediate precision, accuracy, and robustness studies for both the methods were found to be less than 2. Result of paired t-test at 95% confidence level reveals that there is no significant difference between recoveries of drugs, using both methods. The results of the developed chromatographic methods were acceptable assuring that these methods can be successfully applied for routine quality control testing of both bulk and ophthalmic dosage forms, without any interference from the excipients.
Authors:K. K. Akula, B. Chandrasekaran, M. Kaur and S. K. Kulkarni
A new, rapid, and specific reversed phase high-performance liquid chromatographic (RP-HPLC) method involving precolumn derivatization with benzoyl chloride was developed and validated for the estimation of γ-aminobutyric acid (GABA) in rat brain tissue preparations. The derivatization product of GABA was identified by melting point, infrared, and proton nuclear magnetic resonance (1H NMR) spectroscopy to be n-benzoyl GABA. Various parameters which influenced derivatization and elusion were optimized. The chromatographic system consisted of C-18 column with ultraviolet (UV)—photodiode array detection ranging from 210 to 400 nm. Elution with an isocratic mobile phase consisting of 0.025 M disodium hydrogen phosphate buffer—methanol (65:35, v/v; pH 6) at a flow rate of 1 mL min−1 yielded sharp and specific peak of n-benzoyl GABA within 7 min. The method was validated with respect to the linearity, accuracy, precision, sensitivity, selectivity, and stability, wherein the benzoyl derivative of GABA showed stability for 2 months. The lower limit of detection was 0.5 nmol L−1. This novel derivatization procedure for the estimation of GABA with benzoyl chloride was also applied for rat brain tissue preparations that gave highly specific peak and good component recovery. The results show that the method for the determination of GABA by benzoylation using RP-HPLC has good linearity, accuracy, precision, sensitivity, and specificity and is simple and economical to perform.
Authors:A. Ahmad, R. M. A. Khan and K. M. Alkharfy
A rapid, accurate, and sensitive reverse phase high-performance liquid chromatographic method was developed and validated for the simultaneous determination and quantification of glibenclamide and thymoquinone in rat plasma in the presence of internal standard (thymol). Chromatograms were developed with methanol, acetonitrile, and buffer (50:20:30, v/v/v) solvent system on a Symmetry® C18 (5 μm, 3.9 × 150 mm) column, and pH was adjusted to 4.5 with orthophosphoric acid. Mobile phase was pumped at a flow rate of 1.5 mL min−1 with 254 nm ultraviolet (UV) detection. Validation of the method was performed in order to demonstrate its selectivity, linearity, precision, accuracy, limits of detection, and quantification (LOD and LOQ). Standard curves were linear (r2 = 0.996 and 0.999 for glibenclamide and thymoquinone) over the concentration range 0.5–50 μg mL−1. The coefficient of variation (CV) of < 6% and accurate recovery of 87.54–105.19% for glibenclamide and CV of <5% and accurate recovery of 86.08–103.19% for thymoquinone were found to be in the selected concentration range of 0.5–50 μg mL−1. The lower limits of detection and quantitation of the method were 0.109 and 0.332 μg mL−1 for glibenclamide and 0.119 and 0.361 μg mL−1 for thymoquinone, respectively. The within and between-day coefficients of variation were less than 7%. The validated method has been successfully applied to measure the plasma concentrations in a drug interaction study of glibenclamide with thymoquinone in an animal model to illustrate the scope and application of the method.
A new ultra-performance liquid chromatography method for the simultaneous determination of valsartan, amlodipine besylate, and hydrochlorothiazide in pharmaceutical formulations has been developed. Chromatographic separation was achieved within 1 min on a sub-2 μm RP18 column using an isocratic mode mobile phase consisting of a mixture of methanol and phosphate buffer (0.05 M, pH 3 ± 0.05) in the ratio 70:30 (v/v). The flow rate was set at 0.3 mL min−1 with a detection wavelength of 239 nm. The method was validated over the concentration ranges from 6.5 to 15.0 μg mL−1 for hydrochlorothiazide, from 5.0 to 12 μg mL−1 for amlodipine besylate and from 76.5 to 178.5 μg mL−1 for valsartan. Calibration plots were linear for valsartan, amlodipine besylate, and hydrochlorothiazide with a correlation coefficient greater than 0.99. Relative variation coefficients for repeatability and reproducibility were less than 3.0%. Recoveries from standard addition essay of individual component in pharmaceutical formulations were varied from 97.0% to 102.0%. The proposed method was successfully applied for the determination of valsartan, amlodipine besylate, and hydrochlorothiazide in pharmaceutical formulations with recoveries with respect to label amount in pharmaceutical formulations that varied from 98.0% to 102.9%. The low flow rate, short analysis time, and simple mobile phase composition make the method cost effective, rapid, nontedious, and successfully employed for simultaneous determination of these drugs in commercial pharmaceutical products.
Authors:H. M. Albishri, D. Abd El-Hady and Roaa A. Tayeb
Pharmaceutical industry concerned recently with eco-friendly analytical methods to reduce the environmental pollution. The using of toxic organic solvents for the analysis of drugs is critical. In the current work, several simple and less costly approaches such as micellar and/or cyclodextrin liquid chromatography were discussed. A new eco-friendly and simple chromatographic analysis of the ternary mixture of amiloride hydrochloride (AM), atenolol (AT), and hydrochlorothiazide (HZ) in urine by hydroxypropyl-beta-cyclodextrin (HP-β-CD) bonded stationary phase was investigated. The experimental conditions were optimized and validated based on International Conference on Harmonization (ICH) Q2R1 guidelines to detect analytes by isocratic mobile phase of phosphate buffer (5.0 mmol L−1, pH 7.0) in the presence of 0.5 mL min−1 flow rate, 25.0 °C, and 280 nm. Linearity, accuracy, and precision were found to be acceptable over the concentration range of 0.05–20.0 μg mL−1 for AM, 0.05–50.0 μg mL−1 for AT and 0.05–50.0 μg mL−1 for HZ. The proposed method was precise, selective, and sensitive enough for the routine analysis of ternary mixture at therapeutic urine levels. The inclusion complexation and the appendant hydroxyl groups of HP-β-CD were considered the main reasons for assisting in adequate separation of the drugs. On the other hand, the presence of kosmotropic phosphate ions could solubilize the protein and could strengthen the selective inclusion of drugs inside HP-β-CD cavity. Urinary excretion studies showed that the detection of drugs is possible up to 24 h after their ingestion.
Authors:M. R. Hadjmohammadi and S. S. S. J. Nazari
Description of the retention of five aromatic diamines in high submicellar liquid chromatography was carried out through several hyperbolic and logarithmic retention models using the retention data of mobile phases consisting of sodium dodecyl sulfate (SDS) (0.09–0.15 M) and methanol (50–70% v/v) at pH 3. Among the investigated models, the logarithmic retention model 0.5 log k = c0 + c1ϕ + c2[M]+ c12(ϕ[M])0.5 showed the best prediction capability and used to predict the solutes retention factors. The mean relative error of the prediction of retention factors of five aromatic diamines in the selected variables space was lower than 0.5%. Based on the best retention model, a grid search program was used to predict the retention times of each solute for all combinations of SDS and methanol concentrations in the factor space. In order to find optimal separation condition, two different chromatographic goals, analysis time and retention differences between adjacent peaks, were evaluated simultaneously using Derringer's desirability function for each mobile phase composition. At the optimal conditions (0.143 M SDS, 53% v/v methanol), a good agreement was observed between predicted and experimental values of the retention times (R2 = 0.9999 and mean relative error of 0.96%).
The composition of the essential oils obtained by hydrodistillation from flowers of Chrysanthemum coronarium L. has been investigated by gas chromatography-mass spectrometry (GC-MS). A total of 105 different constituents were identified, representing an average of 97.71–99.95% of the total oil composition. The oil obtained from flowers propagated conventionally contained the higher amounts of cis-chrysanthemol, cischrysanthenyl isovalerate, camphor, and virdiflorol, while the higher concentration of bornyl acetate, cis-chrysanthenyl acetate, and 2-(2,4-hexadiynylidene)-1,6-dioxaspiro[4.4] non-3-ene was noted in the oil obtained from flowers propagated in vitro.
Significantly higher amounts of essential oil were obtained from flowers of plants derived for in vitro propagation (0.58%) in comparison with conventional cultivation (0.50%).
Authors:K. Pramod, U. K. Ilyas, M. Singh, Y. T. Kamal, S. Ahmad, S. H. Ansari and J. Ali
High-performance thin-layer chromatography (HPTLC) method for the quantification of eugenol from nanostructured drug delivery systems was successfully developed and validated. The mobile phase consisted of n-hexane:acetone (7:3, v/v), and the densitometric scanning was performed in the absorbance mode at 280 nm. The method was valid with respect to linearity and range, accuracy, precision, specificity, detection limit (DL), and quantitation limit (QL). The linearity of the method was established by a correlation coefficient value of 0.9930 ± 0.0013. The precision was tested by checking intra-day (repeatability) and inter-day (intermediate precision) variations. The method was established to be precise by low relative standard deviation (RSD) values for different concentration of eugenol. The results of the recovery studies of eugenol from preanalyzed samples demonstrated the accuracy of the method. The specificity of the developed method for the analysis of eugenol in the nanoemulsion gel and nanoparticles samples was confirmed by comparing the spectra obtained in standard and sample analysis. The DL and QL were determined to be 31.41 and 95.17 ng band−1, respectively, for the HPTLC method. The forced degradation studies revealed on eugenol established the effectiveness of the developed and validated method. The developed and validated HPTLC method was found to be a stability-indicating one, as indicated by the results of forced degradation studies, for its use during the accelerated stability studies of the nanoemulsion gels and nanoparticles of eugenol.
Authors:X. X. Yu, J. W. Wu, Z. K. Liang, M. Q. Zhao and X. J. Xu
A high-speed counter-current chromatography (HSCCC) method was established for the isolation and purification of isochlorogenic acid A from Lonicera japonica Thunb. The two-phase solvent system was composed of n-hexane:ethyl acetate: isopropanol:water (2:3:2:5, v/v/v/v). From 150 mg of the ethyl acetate fraction of L. japonica Thunb, 19.65 mg of isochlorogenic acid A was obtained in a one-step HSCCC separation, with a purity of 99.1%, as determined by high-performance liquid chromatography (HPLC). The structure was further identified by ultraviolet (UV), mass spectrometry (MS) and nuclear magnetic resonance (NMR).
Authors:T. S. Belal, M. M. Bedair, A. A. Gazy and K. M. Guirguis
This study presents a selective high-performance liquid chromatography (HPLC) with diode array detection (DAD) method for the simultaneous estimation of diclofenac sodium and lidocaine hydrochloride in presence of four of their related substances and potential impurities, namely, 2,6-dimethylaniline (DMA), 2,6-dichloroaniline (DCA), N-phenyl-2,6-dichloroaniline (PDCA), and N-chloroacetyl-N-phenyl-2,6-dichloroaniline (CPDCA). Some of these related substances are reported as degradation products as well. Effective chromatographic separation was achieved using Waters Symmetry C18 column, (3.9 × 150 mm, 5 μm particle size) with gradient elution of the mobile phase composed of 0.05 M orthophosphoric acid and acetonitrile. The gradient elution started with 5% (by volume) acetonitrile, ramped up linearly to 65% in 5 min then kept constant till the end of the run. The mobile phase was pumped at a flow rate of 1.5 mL min−1. The multiple wavelength detector was set at 220 nm, and quantification of both drugs was based on measuring their peak areas. The retention times for lidocaine and diclofenac were about 5.5 and 9.5 min, respectively. The reliability and analytical performance of the proposed HPLC procedure were statistically validated with respect to system suitability, linearity, ranges, precision, accuracy, specificity, robustness, detection, and quantification limits. Calibration curves were linear in the ranges of 10–200 μg mL−1 for both drugs with correlation coefficients not less than 0.9998. The proposed method proved to be selective by resolution of the two drugs from their related substances and potential impurities. The validated HPLC method was successfully applied to the analysis of this binary mixture in the combined formulation (ampoules dosage form), and the assay results were favorably compared with a previously reported HPLC method. The proposed method made use of DAD as a tool for peak identity and purity confirmation.
Authors:R. Divišová, E. Vítová, P. Diviš, J. Zemanová and J. Omelková
An analytical method for simultaneous determination of 24 legislatively restricted fragrance allergens in various cosmetic products was developed and validated using a combination of solid-phase microextraction and gas chromatography with flame ionization detector. The divinylbenzene-polydimethylsiloxane (DVB-PDMS) fiber was evaluated as the best for extraction of all studied fragrance allergens at 40 °C and 20 min extraction time. All calibration curves showed good linearity in the range of 10−1 to 103 μg mL−1. Good repeatability and inter-day precision was determined for the proposed method. Detection limits for individual allergens ranged from 0.007 to 2.7 μg mL−1. The validated method was used to analyze real cosmetic samples. The obtained results indicated that not all of the analyzed cosmetic samples were labeled in accordance with European Cosmetic Directive.
This paper describes the selective and reproducible debenzylation of benzyloxypyrazinones using flow chemistry to yield N-hydroxypyrazinones. Flow methodology enabled us to avoid overreduction of the compounds to pyrazin-2(1H)-ones.
Authors:Robert Green, Richard Brown and Derek Pletcher
In order for microflow electrolysis cells to make their full contribution to routine laboratory organic synthesis, they must be capable of carrying out reactions with good selectivity and high conversion at a high rate of conversion. In addition to appropriate choice of the electrolysis medium and control of the overall cell chemistry, both the design of the electrolysis cell (including materials of construction) and the correct selection of the cell current and flow rate of the solution are critical in determining performance. The conclusions are tested using the methoxylation of N-formylpyrrolidine as the test reaction in a microflow electrolysis cell with a single, long, patterned flow channel.
Authors:Lucia Pirvu, Cristina Hlevca, Ioana Nicu and Corina Bubueanu
Given the large applicability in both pharmaceutical and cosmetic field, this work was aimed at analytical (high-performance thin-layer chromatography [HPTLC] method), antioxidant (2,2-diphenyl-1-picrylhydrazyl [DPPH] method), and antimicrobial (diffusion method on Staphylococcus aureus ATCC 6538, Escherichia coli ATCC 8739, and Candida albicans ATCC 10231) studies on a series of whole vegetal extracts and corresponding aqueous, ethyl acetate and chloroform fractions (selective extracts) prepared from eight plant species growing in Romania. Briefly, it was revealed moderate to certain activity against S. aureus ATCC 6538 and E. coli ATCC 8739 in the case of greater burdock leaves (Arctium lappa), beech leaves (Fagus sylvatica) and great willowherb aerial part (Epilobium hirsutum) whole extracts. Purple loosestrife aerial part (Lythrum salicaria) and sea-buckthorn leaves (Hippophae rhamnoides) whole extracts showed only weak activity against these bacteria, while tarragon aerial part (Artemisia dracunculoides), chokeberries leaves (Aronia melanocarpa) and quince fruit (Cydonia oblonga) whole extracts have not shown activity. Subsequently studies on the selective extracts have revealed that combinations of glycosides of the same aglycones lead to very different antimicrobial properties indicating synergistic effects between polyphenols (demonstrated in the case of Fagus sylvatica extracts) or the contribution of other phytocompounds to the final effect (demonstrated in the case of Arctium lappa extracts) and, secondly, that the glycosyl chain in which they occur may also contribute to the final antimicrobial effect (demonstrated by the fact that the most active vegetal extracts emphasized the dominance of flavonoid monoglycosides). Moreover, inhibitory antimicrobial effects were revealed (Arctium lappa extracts). Finally, none of the studied extracts acted against C. albicans ATCC 10231. Concerning antioxidant activity, DPPH tests indicated high potency of all tested extracts (IC50 measuring from 2.66 to 4.80). Further studies on the most active vegetal extracts which aim to reveal MICs values and potential inhibitory or activatory effects in combination with chemical antibiotics are ongoing.
Authors:Dambarudhar Parida, Christophe A. Serra, Rigoberto Ibarra Gómez, Dhiraj K. Garg, Yannick Hoarau, Michel Bouquey and René Muller
We report on the synthesis of 2-(dimethylamino)ethyl methacrylate by atom transfer radical polymerization (ATRP) in tubular microreactors. Different process parameters, temperature, pressure, and shear rate, were considered to accelerate the reaction. Increase in temperature induced a faster reaction, but controlled nature of ATRP decreased past a threshold value that can be increased up to 95 °C by reducing the residence time. Positive effect of pressure was observed since significant increases in monomer conversion (+12.5 %) and molecular weight (+5,000 g/mol) were obtained. Moreover, polydispersity index was found to decrease from 1.52 at normal pressure to 1.44 at 100 bars. Benefit of pressure was more visible in smaller reaction space (smaller tube diameter). Finally, shear rate has quite an influence on the early stage of the polymerization and is expressed by an increase in the reaction rate. However, the effect was dimed for long residence times.
The covalent chemistry of carbon nanostructures has put forth a wide variety of interesting derivatives that widen their potential as functional materials. However, the synthetic procedures that have been developed to functionalize the nanostructures may require long reaction times and harsh conditions. In this paper, we study the continuous flow processing of single-wall carbon nanotubes with azomethine ylides and diazonium salts and demonstrate that this approach is effective to reduce reaction times and tune the properties of the functionalized carbon materials.
Authors:Isabelle Kraus, Shuning Li, Andrea Knauer, Marc Schmutz, Jacques Faerber, Christophe A. Serra and Michael Köhler
This paper presents a new route to the synthesis of uniform and size-controlled inorganic/organic composite microparticles by means of microreaction technology. Au-nanoparticles in the range of 3 to 14 nm are synthesized by reduction of tetrachloroauric acid, while ZnO-nanoparticles (200–2000 nm) are synthesized in a continuous-flow two-step process using microtube arrangements for microsegmented flow. Both inorganic nanoparticles have a well-controlled size and narrow size distribution. Upon surface modification, the nanoparticles are then mixed on one hand with an acrylate-based monomer and, on the other hand, with an aqueous solution of acrylamide. Both solutions were then emulsified into uniform core-shell droplets by means of a capillary-based microfluidic device. Droplet's shell was hardened through UV-induced polymerization, whereas the core led to a hydrogel upon thermal-induced polymerization. Core-shell polymer microparticles (200–300 µm) with inorganic nanoparticles selectively incorporated into the core and the shell are thus obtained as proven by extensive morphological characterizations using electronic and optical microscopies.
In this section of the journal, the continuous-flow chemistry literature of the preceding months is presented. Included are articles published in the period October–December 2013 and January–March 2014. Some key examples are highlighted in the form of graphical abstracts. The remaining publications in the field are then listed ordered by journal name, with review articles grouped at the end.
Authors:Mohammed Kechadi, Mathilde Faure, Bruno Sotta and Jean Gamby
The real-time monitoring of the adsorption kinetic of antibody onto polyethylene terephthalate (PET) modified with gold nanoparticles (NPs) is performed into a dielectric flow microchannel. The principle is based on the microelectrode–dielectric interface excitation by a modulated voltage excitation through the dielectric layer with high frequency range. The set-up configuration using a homemade current-to-voltage converter has been developed for fast monitoring of biomolecule adsorption without direct electrical contact of microelectrodes with the microchannel flow. The change in the interfacial admittance, related to the output voltage measured through the microchip, during antibody incubation, gives information on the kinetics involved while antibodies are adsorbed at the interface. An example of adsorption on PET modified with gold NPS was taken. Experimental data were fit with the Langmuir equation and a good correlation was obtained with this latter, where the equilibrium constant, K, was found as 1.55 × 108 M−1 with a limit of detection for antibody concentration without depletion equal to 8.25 nM.
Authors:Omar Pandoli, Tommaso Del Rosso, Ricardo Queiroz Aucélio, Alessandro Massi, Chen Xiang and Shu-Ren Hysing
A novel micromixer concept for generation of concentration gradients, inspired by a Chinese design, the traditional Chinese knot “中国结”, which features a core mesh structure allowing for a very compact design, is presented. The new concept has been designed using modern computer-aided design (CAD) and computational fluid dynamics (CFD) simulation software and validated by performing multiple experiments. The final design is found to be significantly more compact than conventional ones and allows the use of up to 15 outlet channels.
Authors:Giancarlo Pascali, Mariarosaria De Simone, Lidia Matesic, Ivan Greguric and Piero A. Salvadori
Nucleophilic [18F]-fluorination reactions traditionally include a drying step of the labeling agent in order to achieve a successful substitution. This passage extends the time and complexity required for the whole radiotracer production, with increased hardware and detrimental effects on the radioactive recovery of such a short-lived (t½=109 min) isotope. Because the performance of radiofluorination reactions conducted under microfluidic flow conditions have been demonstrated to be more effective in terms of reaction time and yields, we have tested the tolerance to water present in this specific reaction condition, in view of eliminating the drying step in the process. To this purpose, we tested different substrates selected from typical radiofluorination intermediates. Our results show that water could be tolerated in a microfluidic environment; in particular, we observed a slight decrease in the labeling of aromatic precursors and a significant increase for iodonium salts, whereas the radiochemical yields of the other compounds studied were virtually unchanged. These findings may open the way to the possibility of simpler and faster processes for the production of new 18F-fluorinated positron emission tomography tracers.
Authors:Kimitada Terao, Yasuhiro Nishiyama and Kiyomi Kakiuchi
An asymmetric Paternò–Büchi-type photoreaction between 2,3-dimethyl-2-butene and benzoylformic acid ester with a chiral menthyl auxiliary was studied in a continuous-flow microcapillary reactor. The fluorinated ethylene propylene (FEP) microcapillary reactor using normal one-layer flow mode gave oxetane products with better efficiency than the batch system. In addition, the slug flow mode in microcapillary reactor using inactive reagent, N2 gas or H2O, improved the reaction efficiency dramatically because of synergistic light dispersion, stirring and thin layer film effects. The reaction efficiencies under each condition were discussed as energy efficiencies calculated from reactors' parameters.
Authors:F. Wang, S. Liu, M. Luo, Y. Qin, P. Lei, Y. Liu and Y. Liang
The essential oil extracted from Nardostachys chinensis Batal (NCB) was analyzed by gas chromatography-mass spectrometry (GC-MS) combined with two chemometric resolution methods (CRM), heuristic evolving latent projections (HELP), and selective ion analysis (SIA). Qualitative analysis was performed by comparing the obtained pure mass spectra with those in National Institute of Standards and Technology (NIST) mass spectra database. Identification of some compounds was assisted by comparison of programmed temperature retention indices (PTRIs). The quantitative results were obtained by overall volume integration (OVI). A total of 69 compounds in the essential oil of N. chinensis Batal were identified, accounting for 93.98% of the total content. The major compounds were (−)-spathulenol, epiglobulol, trans-longipinocarveol, and patchouli alcohol which contribute to the antimicrobial and antioxidant activity. The results showed that the efficiency and reliability were greatly improved by use of chemometric techniques and programmed temperature retention index as assistants of GC-MS in identification of the plant essential oil.
Authors:D. Krasucka, C. Kowalski, M. Osypiuk and G. Opielak
A high-performance liquid chromatographic (HPLC) method with fluorescence detection after precolumn formaldehyde derivation was developed to detect concentrations of amoxicillin (AMX) in poultry plasma. Proteins in plasma samples spiked with AMX were precipitated with a phosphate buffer and trichloroacetic acid. After precolumn treatment of the extraction product of AMX with formaldehyde under acidic and heating conditions, HPLC analysis with fluorescence (FL) detection at an excitation wavelength of 355 nm and an emission wavelength of 450 nm was performed. A mobile phase comprising acetonitrile and a buffer solution (0.05 M KH2PO4 pH = 5.6), which yielded AMX retention time 8.58 min, was suitable for detection of AMX. The calculated standard curve of the reaction product was linear, and the correlation coefficient was greater than 0.999. The limit of detection and quantification, the accuracy, and the precision were evaluated. Recoveries of spiked amoxicillin were >92%, with a coefficient of variation in the range of 0.35–0.89%. This method has been successfully applied to a pharmacokinetic study after oral administration of amoxicillin to poultry.
Authors:Y. Wang, M. Wang, J. Li, S. Yao, J. Xue, W. Zou and C. Hu
An improved ion-pairing reversed-phase high-performance liquid chromatography method coupled with evaporative light scattering detection (HPLC-ELSD) was developed to determine spectinomycin and its related substances in commercial samples. The method was validated in accordance with International Conference on Harmonization (ICH) guidelines. The specificity of the HPLC-ELSD method was similar to that of the European Pharmacopoeia (Ph. Eur.) method, and repeatability and robustness were markedly improved relative to other reported methods due to our empirical evaluation of separation columns. Indeed, it is a more specific assay of spectinomycin than traditional microbiological techniques. The HPLC-ELSD method was used to evaluate the impurity profiles of eight compounds in seven spectinomycin batches from five different companies. Liquid chromatography coupled with electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS) was employed to characterize the structures of these compounds. Though the HPLC-ELSD method was not as sensitive as the Ph. Eur. method, its limit of quantitation (LOQ) (0.16%) was lower than the disregard limit (0.3%) described by the Ph. Eur. 7.0. This suggests that the HPLC-ELSD method is appropriate for routine analysis of spectinomycin and its related substances.
Authors:H. Mahgoub, A. Hanafy, F. Bamane and A. Radwan
A sensitive and reproducible high-performance liquid chromatographic (HPLC) method for determination of talinolol (TAL) in rat plasma was developed and validated using pindolol (PIN) as an internal standard. Both TAL and PIN were separated on a Zorbax Eclipse XDB C18 column by gradient elution with 0.1% aqueous formic acid and acetonitrile as the mobile phase. Detection was performed using fluorescence measurement at λex 249 nm and λem 333 nm. The method was validated and found to be linear in the range of 10–2000 ng mL−1. The limit of quantification was 10 ng mL−1 based on 100 μL of plasma. The variations for intra- and inter-day precision were less than 10%, and the accuracy values were between 92% and 102.9%. The extraction recoveries were more than 82%. The assay was successfully applied to an in-vivo pharmacokinetic study of TAL in rats that were administered a single oral dose of 10 mg kg−1 TAL. The maximum concentration (Cmax) and the area under the plasma concentration-time curve (AUC0–12) were 0.369 ± 0.024 μg mL−1 and 1.429 ± 0.027 μg h mL−1, respectively. The modulatory effect of apricot juice on P-glycoprotein-related efflux carriers was also investigated. Co-administration of apricot juice resulted in a significant increase of the amount of TAL in plasma (Cmax and AUC0–12 were 0.679 ± 0.021 and 2.357 ± 0.079, respectively; p < 0.05).
A microextraction procedure based on ultrasound-assisted surfactant-enhanced emulsification microextraction (UASEME) was optimized and validated for preconcentration of carbamate pesticides prior to fast determination using high-performance liquid chromatography (HPLC) with monolithic column. The nonionic surfactant (Tween 20) was used as an emulsifier, and chloroform was selected as an extraction solvent. The experimental parameters affecting the extraction efficiency, such as the kind, concentration, and volume of surfactant, the kind of extraction solvent and its volume, salt addition, ultrasonic extraction time, and centrifugation time, were optimized. Under the selected UASEME and HPLC conditions, separation of five carbamate pesticides (carbofuran, carbaryl, isoprocarb, methiocarb, and promecarb) was achieved within 10 min. The linearity of the method was obtained in the wide range of 2–5000 μg L−1, with correlation coefficients of 0.9931–0.9970. The limits of detection were in the range of 0.4–7.0 μg L−1. The relative standard deviations (n = 5) were less than 0.59% and 4.86% for retention time and peak area, respectively. The enrichment factors of the developed UASEME method were in the range of 33–166. The fruit juice samples (at fortified levels of 0.25, 0.50, and 1.00 mg L−1) were successfully analyzed, and the relative recoveries were obtained in the range of 81–115%.
Authors:W.-Y. Liu, M.-L. Wei, C.-Y. Wu, H.-Y. Zhu, F. Feng and N. Xie
Patrinia scabra Bunge has long been used in clinic as a traditional Chinese medicine for treating leukemia and cancer and regulating host immune response. Despite their wide use in China, no report on system analysis on their chemical constituents is available so far. The current study was designed to profile the fingerprint of ethyl acetate extract of it, and in addition, to characterize the major fingerprint peaks and determine their quantity. Therefore, a detailed gradient high-performance liquid chromatography was described to separate more than 30 compounds with satisfactory resolution in P. scabra Bunge. Based on the chromatograms of 10 batches samples, a typical high-performance liquid chromatographic (HPLC) fingerprint was established with 23 chromatographic peaks being assigned as common fingerprint peaks. Furthermore, a quadrupole time of flight mass spectrometry (Q-TOF/MS) was coupled for the characterization of major compound. As (+)-nortrachelogenin was the most predominant compound in P. scabra Bunge, the quantification on it was also carried out with the method being validated. As a result, (+)-nortrachelogenin was found to be from 1.33 to 2.21 mg g−1 in this plant material. This rapid and effective analytical method could be employed for quality assessment of P. scabra Bunge, as well as pharmaceutical products containing this herbal material.
Authors:C. Wen, Q. Zhang, Y. He, M. Deng, X. Wang and J. Ma
A sensitive and simple liquid chromatography-electrospray ionization-mass spectrometry (LC-ESI-MS) method for determination of dasatinib in rat plasma using one-step protein precipitation was developed. After addition of carbamazepine as internal standard (IS), protein precipitation by acetonitrile was used as sample preparation. Chromatographic separation was achieved on an SB-C18 (2.1 mm × 150 mm, 5 μm) column with methanol-0.1% formic acid as mobile phase with gradient elution. Electrospray ionization (ESI) source was applied and operated in positive ion mode; selective ion monitoring (SIM) mode was used to quantification using target fragment ions m/z 488.2 for dasatinib and m/z 338.7 for the IS. Calibration plots were linear over the range of 10–1000 ng mL−1 for dasatinib in rat plasma. Lower limit of quantification (LLOQ) for dasatinib was 10 ng mL−1. Mean recovery of dasatinib from plasma was in the range 82.2%–93.6%. Relative standard deviation (RSD) of intra-day and inter-day precision were both less than 8%. This developed method is successfully used in pharmacokinetic study of dasatinib in rats.
The metal-organic framework (MOF) is a kind of new type self-assembly porous coordination polymer, which possesses many characteristics such as homologic hole, controllable size of cave, high specific surface area, and good chemical stability. In this study, a three-dimensional framework [Zn2(d-Cam)2(4,4′-bpy)]n with large homochiral channel and the orderly arrangement of left- and right-handed helices was used as chiral stationary phases (CSPs) in gas chromatography (GC). [Zn2(d-Cam)2 (4,4′-bpy)]n-coated open tubular column was prepared by a dynamic coating method for high-resolution GC. Some racemates, isomers, linear alkanes, and alcohols are used as the targets for separation. The column coating properties efficiency, polarity, and selectivity were studied. The experimental results show that the stationary phase has outstanding selectivity and also possesses good recognition ability toward these compounds.
Authors:P. Srivastava, H. Raut, H. Puntambekar and A. Desai
Storage of medicinal plants may cause deterioration of the active principles with time, thus, reducing the efficacy of plants. Therefore, quantification of the active principle is essential before using the crude drug. Phyllanthus amarus (PA) contains lignans, namely, phyllanthin and hypophyllanthin, which shows anti-hepatotoxic activity. In this paper, we highlight the effect of storage conditions on the quantification of bioactive markers by high-performance liquid chromatography (HPLC) analysis in the crude plant material of PA. HPLC analysis of crude PA samples stored for certain period at long-term study (LS, 30 °C and 65% RH), accelerated study (AS, 40°C and 75% RH), and real-time study (RT) conditions was carried out using the LiChroCART Purospher® STAR RP-18 endcapped (250 × 4.6 mm, 5 μm) column along with a Purospher STAR RP 18e (4.0 × 4.0 mm, 5 μm) guard column using methanol:water (70:30) at a flow rate of 0.7 mL min−1 with ultraviolet (UV) detection at 220 nm. The HPLC study indicated that PA samples kept under LS condition are rich in lignan contents as compared to the samples stored under AS and RT study conditions. Therefore, PA should be used fresh to get maximum concentration of active lignans or it should be stored under LS conditions up to 6 months.
Acetyl salicylic acid (ASA), as the major drug consumed in the world, has been combined with other various drugs. In this regard, ASA-rosuvastatin is the most recent combination. The current article reported the first two separation methods for the assay of that combination utilizing sequential injection chromatography (SIC) and high-performance liquid chromatography (HPLC). The optimization process was conducted for SIC, and the optimum conditions were then adapted to HPLC. Both methods, SIC and HPLC, were validated and successfully applied to tablet formulation. In both methods, the analytes were chromatographed onto a short C18 monolithic column (4.6 × 25 mm) by a mobile phase composition of 10 mmol L−1 phosphate:acetonitrile: methanol (50:30:20, v/v/v at pH 3.0). The performances of both methods were compared. The remarkable advantages of the SIC method over HPLC method were the reduction in reagent consumption and instrumentation simplicity and cost-effectiveness. The total volume of mobile phase consumed is three orders of magnitude larger in HPLC than that in SIC. Other analytical features of the SIC and HPLC methods were comparable and acceptable for pharmaceutical analysis. Accordingly, the SIC method could be more suitable for routine analysis of simple matrices after examining the capability of the technique to work under industrial conditions.
Authors:R. Gwarda, A. Tomczyszyn, A. Misicka and T. Dzido
Influence of the following variables such as adsorbent type, type and concentration of organic modifier in mobile phase, type and concentration of ion-pairing reagent, or pH of the mobile phase buffer on retention of some synthetic peptides in reversed-phase high-performance thin-layer chromatography systems has been investigated. The investigations have been also focused on influence of the variables mentioned on solute zone shape regarding optimization of their separation. Remarks about solute retention mechanism have been also provided.
Authors:M. Abdelhay, A. Gazy, R. Shaalan and H. Ashour
A simple and selective liquid chromatographic method was developed for the simultaneous determination of tenofovir disoproxil fumarate (TEN) and emtricitabine (EMT) in combined tablets. The method is based on separation of TEN and EMT on a Zorbax SB-C8 column, 5 μm, 4.6 × 250 mm, with a mobile phase consisting of 50 mM disodium hydrogen phosphate-acetonitrile (50:50, v/v). The mobile phase contains 0.1% triethylamine (TEA) and was adjusted to pH 6.0. Quantification of the analytes is achieved with diode array — ultraviolet detector (DAD-UV) at 260 and 280 nm for TEN and EMT, respectively, based on peak area. Different variables affecting the method were carefully investigated and optimized. Reliability and analytical performance of the proposed method, including linearity, range, precision, accuracy, and detection and quantitation limits, were statistically validated. The high-performance liquid chromatography (HPLC) method was successfully applied for determination of each drug in their binary tablets.
A novel, rapid, and sensitive liquid chromatography-tandem mass spectrometric method was developed and validated for the simultaneous quantification of tenofovir, emtricitabine, and efavirenz in human plasma. Nevirapine was used as an internal standard. The analytes and the internal standard were extracted from human plasma sample by solid-phase extraction technique (SPE). The reconstituted samples were chromatographed on a Chromolith ROD C18 column (50 × 4.6 mm; 5 μ) by gradient elution using a mixture of ammonium acetate buffer (5 mM) and 0.1% formic acid in acetonitrile as the mobile phase at a flow rate of 1.0 mL min−1. The calibration curve obtained was linear (r2 ≥ 0.9990) over the concentration range of 2.5–650 ng mL−1 for tenofovir and 10–4000 ng mL−1 for emtricitabine and efavirenz. The results of the intra- and inter-day precision and accuracy studies were well within the acceptable limits. A run time of 2.5 min for each sample made it possible to analyze more than 300 plasma samples per day. The proposed method was found to be applicable to clinical studies, and the authenticity in the measurement of clinical data is demonstrated through incurred samples reanalysis (ISR).
Authors:Dominique Roberge, Christian Noti, Eberhard Irle, Markus Eyholzer, Bruno Rittiner, Gerhard Penn, Gottfried Sedelmeier and Berthold Schenkel
After a short section of safety aspects related to 2-nitroethanol, the paper describes a powerful methodology for developing flow processes based on a proof of concept (1), an optimization and modeling analysis (2), and a long run study in a mini-plant (3). The proof of concept is the initial stage where the solubilities and concentrations are fixed, taking into account the rough kinetics with a mass transfer understanding. It is followed by a complete kinetic analysis including activation energy to model the reaction under various conditions to optimize different targets (yield not being the only driver!). The last section shows the operation of a mini-plant including a microreactor and work-up unit operations. The approach is extremely powerful as it enables the study at laboratory scale of all the features that are usually associated with a pilot plant namely: stability over time on stream, solvent recirculation, model prediction, and robustness.
Authors:Brecht Egle, Juan Muñoz, Nerea Alonso, Wim De Borggraeve, Antonio de la Hoz, Angel Díaz-Ortiz and Jesús Alcázar
The first example of an alkyl–aryl Negishi coupling in a practical, sustainable, and high-yielding process using a silica-supported catalyst in flow is described. Excellent conversions and good functional group compatibility were obtained under very mild conditions. Functionalized alkyl groups were also introduced to provide access to synthetically useful molecules and to demonstrate the versatility of the method. The scalability was assessed, and a throughput of 7.5 mmol/h of processed substrate was achieved. All crude products were free from phosphine derivatives and ready for use in subsequent reaction steps.
In this study, the influence of glycols on chemical structure and thermal stability of glycolysates as polyurethane intermediates were investigated. The intermediates were obtained by the glycolysis process of waste polyurethane foams in the reaction with different glycols ranging from ethylene glycol to hexane-1,6-diol. The used glycols were not separated from the product after the glycolysis process has been terminated. The effects of different weight ratio of glycols to polyurethane (PU) foam on chemical structure and thermal stability were investigated by FTIR, GPC, and TG/DTG. FTIR analysis of the glycolysates revealed their similar chemical architecture as manifested by the similarity of absorption peaks within the entire wavenumber range of spectra. This may indicate that the glycol has no influence on the chemical composition of glycolysates. GPC analysis showed that the glycolysates were characterized by polydispersity smaller than 2 which is lower as compared to some commercial polyols used for PU synthesis. GPC chromatograms showed that the applied glycols and the conditions of PU glycolysis allowed recreation of the original polyol as documented on the chromatograms by a single, well-formed peak at the beginning of retention time. Based on TG thermograms, it was established that glycol used in transesterification of PUs affected the temperature at which the loss of glycolysate mass by 5 and 10 % occurs. It was also observed that glycol affected the temperature at which the decomposition rate of glycolysates was the highest.
This study contains mathematical modelling and numerical analysis of heat transfer in laser beam welding process. The temperature field was obtained on the basis of numerical solution into unsteady heat transfer equation with convective term and volumetric heat sources taken into account. Volumetric heat source model describing laser beam power distribution in combined truncated cone–cylinder volume was developed. Due to the wide range of temperatures appearing in the process latent heat of fusion, evaporation as well as latent heat of phase transformations in solid state were taken into account in the solution algorithm. On the basis of developed numerical algorithms an analysis of heat transfer in laser butt-welded steel sheets as a three-dimensional initial-boundary problem was performed.
New Y(III) and La(III) complexes with 4-bpy (4,4′-bipyridine) and trichloro- or dibromoacetates with the formulae: Y(4-bpy)2(CCl3COO)3·H2O I, La(4-bpy)1.5(CCl3COO)3·2H2O II, Y(4-bpy)1.5(CHBr2COO)3·3H2O III, and La(4-bpy)(CHBr2COO)3·H2O IV were prepared and characterized by chemical, elemental analysis, and IR spectroscopy. Conductivity studies (in methanol, dimethyloformamide, and dimethylsulfoxide) were also described. They are small, crystalline substances. The way of metal–ligand coordination was discussed. The thermal properties of complexes in the solid state were studied by TG-DTG techniques under dynamic flowing air atmosphere. TG-FTIR system was used to analyze principal volatile thermal decomposition and fragmentation products evolved during pyrolysis in dynamic flowing argon atmosphere for La(III) compounds.
Authors:Przemysław Rybiński, Grażyna Janowska, Małgorzata Jóźwiak and Agnieszka Pająk
This paper presents the effect of halloysite intercalated with a base or modified montmorillonite on the thermal properties and flammability of peroxide and sulfur vulcanizates of styrene–butadiene rubber (SBR). Based on the test results obtained by means of thermal analyses (DTA, TG, DTG, and DSC), oxygen index and microcalorimeter (FAA) it has been found that the thermal stability and flammability of the nanocomposites investigated depend on the spatial network structure as well as the content and type of nanoadditive in the vulcanizate obtained. The nanofillers used considerably reduce the flammability and fire hazard of the cross-linked SBR.
Authors:Joanna Wiśniewska, Grzegorz Wrzeszcz, Stanisław Koter and Tomasz Ligor
The kinetics of the oxidation of imipramine and opipramol using peroxydisulfate salts in the presence of a large excess of dibenzoazepine derivative (TCA) in acidic sulfate media was studied using UV–vis spectroscopy. The reaction between imipramine and S2O82− proceeds via the formation of two intermediates: a free organic radical and a dimeric dication. Further reaction of the intermediate dimeric dication leads to a positively charged radical dimer as one final product. Simultaneously, two other substituent cleavage degradation processes occur, leading to two dimeric derivatives. The first product, the positively charged radical dimer, and the next main product, a radical dimer without one alkyl substituent, were identified by EPR measurements. The measured kinetic trace is not first order and revealed a sigmoid shape with a characteristic induction time. The rate constants were determined by numerical analysis based on ordinary differential equations (ODEs). The reaction between opipramol and S2O82− proceeds by a two consecutive reaction scheme. The kinetics of the first degradation step were studied independently of the slower degradation reactions. Linear dependences, with zero intercept, of the pseudo-first-order rate constants (kobs) on [TCA] were determined for the first degradation process of opipramol.
Authors:Ping He, Stephen J. Haswell, Paul D. I. Fletcher, Stephen M. Kelly and Andrew Mansfield
A highly scalable and efficient flow-system has been developed to perform the catalyzed acetylation of alcohols and phenols, such as salicylic acid, at room temperature in excellent yield. The volumetric throughput and the amount of product can be increased simply by increasing the diameter of a versatile catalytic 12-tungstosilicic acid-supported, silica monolith can be used to increase the quantity of product produced without having to changeing the optimal operatingreaction conditions.
In this section of the journal, the continuous flow chemistry literature of the preceding months is presented. Included are articles published in January and February 2012 and some articles from 2011 which received page numbers only in the beginning of 2012. Some key examples are highlighted in the form of graphical abstracts. The remaining publications in the field are then listed ordered by journal name, with review articles grouped at the end.
Authors:Paul Watts, Giancarlo Pascali and Piero A. Salvadori
Positron emission tomography (PET) is a very powerful diagnostic technique routinely used in a variety of medical applications. This review article summarises the developments of using microreactor technology for the radiochemical synthesis of PETagents. The advantages of manufacturing these imaging drugs using microreactors are described, and a review of reactions conducted to date is outlined.
Authors:Jeremy L. Steinbacher, Yankai Lui, Brian P. Mason, William L. Olbricht and D. Tyler McQuade
We present and validate simple mesofluidic devices for producing monodisperse droplets and materials. The significance of this work is a demonstration that simple and complex droplet formulations can be prepared uniformly using off-the-shelf small-diameter tubing, barbed tubing adapters, and needles. With these simple tools, multiple droplet-forming devices and a new particle concentrator were produced and validated. We demonstrate that the droplet-forming devices could produce low-dispersity particles from 25 to 1200 Km and that these results are similar to results from more complicated devices. Through a study of the fluid dynamics and a dimensional analysis of the data, we have correlated droplet size with two dimensionless groups, capillary number and viscosity ratio. The flowfocusing device is more sensitive to both parameters than the T-junction geometry. The modular character of our mesofluidic devices allowed us to rapidly assemble compound devices that use flow-focusing and T-junction devices in series to create complex droplet-in-microcapsule materials. This work demonstrates that flow chemistry does not require complicated tools, and an inexpensive tool-kit can allow anyone with interest to enter the field.
Authors:Oksana Shvydkiv, Carolin Limburg, Kieran Nolan and Michael Oelgemöller
Photooxygenation of 1,5-dihydroxynaphthalene to Juglone was studied in a falling film microreactor. Moderate conversion rates of up to 31% were achieved after just 160 s of exposure to visible light. In contrast, batch reactions gave much lower conversions of up to 14% after a prolonged time period of 10 min. The difference in performance is explained by the superior light penetration in the microfilm and the large gas-liquid contact area.
Authors:Ana Cukalovic, Jean-Christophe M. Monbaliu, Geraldine J. Heynderickx and Christian V. Stevens
The Kiliani reaction, i.e. the elongation of the carbon chain by means of cyanide addition to the carbonyl group of carbohydrate derivatives, is studied on lower C3-, C4- and C6-ketoses under continuous flow conditions. Depending on the process parameters, the corresponding cyanohydrins or α-hydroxycarboxylic acids are obtained. A simple on-line purification of the effluent is studied using cation exchange resins. Reactions provide high yields and selectivity within short residence times, emphasizing the assets of the continuous flow process versus the batch process.
Authors:Jerzy J. Chruściel, Grażyna Janowska and Marzena Fejdyś
New branched polymethylvinylborosiloxanes (PMVBSs) with random structures were prepared, and their chemical structures were studied by spectroscopic methods (FTIR, 1H-, 29Si-, and 11B-NMR) and elemental analysis (% C, % H, % Si, and % B). Average molecular weights Mw and Mn were determined by a size exclusion chromatography (SEC), and dynamic viscosities were measured in Brookfield cone–plate reoviscometer HBDV-II+cP. Thermal properties of PMVBSs were studied under air and under nitrogen atmosphere. Thermal curves were interpreted from the point of view of physical and chemical transitions, taking place during the heating process of PMVBSs. Parameters of their thermal stabilities and glass transition temperatures (Tg) were determined. The synthesized PMVBSs are characterized by low glass transition temperatures (Tg: from −122 to −137 °C) which depend on their chemical structures. It was concluded that gaseous products (such as volatile siloxanes, silanes, CO2, H2O, CH2O, methanol, and formic acid), which could be liberated during the heating process of PMVBSs, promote ceramization processes, leading to the formation of the ceramics of a type SiBCO—a borosilicate glass and silica.
The work considers the methods and techniques, allowing the assignment of the kinetic mechanisms to the chemical reactions evaluated from signals of thermoanalytical measurements. It describes which information about the kinetic mechanisms can be found from either model-free or model-based methods. The work considers the applicability of both methods and compares their results. The multiple-step reactions with well-separated peaks can be equa