Preparation of a polydopamine/ß-cyclodextrin coated open tubular capillary electrochromatography column and application for enantioseparation of five proton pump inhibitors.

An open tubular capillary electrochromatography column was prepared by immobilizing ß-cyclodextrin on the inner wall of pretreated capillary via noncovalent adsorption of polydopamine. The resulting coating layer on the capillary was characterized by scanning electron microscopy and Fourier transform infrared spectroscopy. Electroosmotic flow was studied to evaluate the variation of the immobilized columns. The prepared columns showed good chiral separation performance toward five proton pump inhibitors including lansoprazole, pantoprazole, tenatoprazole, rabeprazole, and omeprazole. The influences of ß-cyclodextrin concentration, coating time, buffer pH, buffer concentration, and applied voltage on separation were investigated. In the optimum conditions, the enantiomers of five analytes were fully resolved within 15 min with high resolutions of 4.57 to 8.13. The method was extensively validated in terms of accuracy, precision, and linearity and proved to be robust. The relative standard deviation values for migration times and peak areas of the analytes representing intraday and interday were less than 1.9 and 3.6%, respectively. Further, the polydopamine/ß-cyclodextrin coated capillary column could be successively used over 100 runs without showing significant decrease in the separation efficiency.

Validated Simultaneous Gradient Ultra-Performance Liquid Chromatographic Quantification of Some Proton Pump Inhibitor Drug Residues in Saudi Pharmaceutical Industrial Wastewater.

Monitoring and quantification of active pharmaceutical ingredients (APIs) in the environment constitute important and challenging tasks, as they are directly associated with human health. Three commonly used proton pump inhibitors (PPIs), namely, omeprazole sodium (OMP), pantoprazole sodium (PNT), and lansoprazole sodium (LNZ) are well separated and quantified using ultra-performance liquid chromatography (UPLC) in pharmaceutical industrial wastewater. The separation of the studied drugs was performed on a stationary phase with a WatersTM column (100 × 2.1 mm, 1.7 µm). The mobile phase was composed of methanol:0.05 M potassium dihydrogen phosphate buffer (adjusted to pH 7.5 using NaOH) (50:50, v/v). The elution process was done in gradient mode by changing the relative proportions of the mobile phase components with time to get an optimum separation pattern. The flow rate of the developing system was adjusted to 0.8 mL/minute. Detection of the separated drugs was performed at 230 nm. The studied drugs were quantified in the concentration range of 10-200 ng/mL for all drugs. The cited method was fully validated according to the international conference on harmonization (ICH-Q2B) guidelines, then it was applied successfully for quantification of the studied PPIs in real wastewater samples after their solid phase extraction (SPE).

Solid-phase extraction combined with dispersive liquid-liquid microextraction and chiral liquid chromatography-tandem mass spectrometry for the simultaneous enantioselective determination of representative proton-pump inhibitors in water samples.

This report describes, for the first time, the simultaneous enantioselective determination of proton-pump inhibitors (PPIs-omeprazole, lansoprazole, pantoprazole, and rabeprazole) in environmental water matrices based on solid-phase extraction combined with dispersive liquid-liquid microextraction (SPE-DLLME) and chiral liquid chromatography-tandem mass spectrometry. The optimized results of SPE-DLLME were obtained with PEP-2 column using methanol-acetonitrile (1/1, v/v) as elution solvent, dichloroethane, and acetonitrile as extractant and disperser solvent, respectively. The separation and determination were performed using reversed-phase chromatography on a cellulose chiral stationary phase, a Chiralpak IC (250 mm × 4.6 mm, 5 µm) column, under isocratic conditions at 0.6 mL min(-1) flow rate. The analytes were detected in multiple reaction monitoring (MRM) mode by triple quadrupole mass spectrometry. Isotopically labeled internal standards were used to compensate matrix interferences. The method provided enrichment factors of around 500. Under optimal conditions, the mean recoveries for all eight enantiomers from the water samples were 89.3-107.3 % with 0.9-10.3 % intra-day RSD and 2.3-8.1 % inter-day RSD at 20 and 100 ng L(-1) levels. Correlation coefficients (r (2)) ≥ 0.999 were achieved for all enantiomers within the range of 2-500 µg L(-1). The method detection and quantification limits were at very low levels, within the range of 0.67-2.29 ng L(-1) and 2.54-8.68 ng L(-1), respectively. This method was successfully applied to the determination of the concentrations and enantiomeric fractions of the targeted analytes in wastewater and river water, making it applicable to the assessment of the enantiomeric fate of PPIs in the environment. Graphical Abstract Simultaneous enantioselective determination of representative proton-pump inhibitors in water samples.

Uneven Distribution of Microgranules in Divided Lansoprazole Tablets.

OBJECTIVES: Lansoprazole is a proton pump inhibitor commonly used in children <12 months of age despite a lack of efficacy and safety data in this age group. To achieve lower doses in this population, many divide standard oral disintegrating tablets. This study seeks to determine if the medication is equally distributed within the tablet to allow for accurate dosing. METHODS: Ten 15-mg Prevacid SoluTabs were divided. Each portion was dissolved separately (half A, B, and the residual "dust" C) and photographed. A magnified view of the image allowed for counting each microgranule. RESULTS: The mean number and standard deviation of microgranules in half A, B, and part C were 2514.7 ±â€Š130.5, 2342.9 ±â€Š130.1, and 49.4 ±â€Š38.8, respectively. The total number of microgranules per tablet was 4907 ±â€Š140.5. There was a statistically significant difference in the mean number of microgranules in half A versus B (P = 0.0086). CONCLUSIONS: There are statistically significant differences in the amount of lansoprazole-containing microgranules within each half of a divided tablet. Clinicians must determine whether this difference is clinically relevant when prescribing "divided" medication to children.

Development and validation of a UPLC method for rapid and simultaneous analysis of proton pump inhibitors.

Proton pump inhibitors (PPIs) are used extensively for the relief of gastroesophageal reflux, peptic ulcers, and other hypersecretory conditions. Some of the commonly used PPIs-omeprazole, esomeprazole, lansoprazole, pantoprazole, and rabeprazole-were used in this study with the aim of developing a rapid ultra performance liquid chromatography (UPLC) method for detecting each and allowing separation and quantification of a mixture of PPIs. An analysis of samples was performed on a UPLC system equipped with a quaternary solvent delivery system, a refrigerated sample manager, a column heater, a photo diode array detector scanning from 210 to 400 nm, and a C18 analytical column (50 mm × 3.0 mm, 1.7-µm particle size). The chromatographic analysis of the PPI samples and standards was performed using gradient elution with acetonitrile and water. The calibration curve range varied for each of the PPIs ranging from a lower limit of 0.75-1.78 µg/mL to a maximum concentration of 200 µg/mL with a regression coefficient (r (2)) of ≥0.98. The accuracy and precision were calculated, and the %RSD was determined to be ≤0.21% (intraday) and ≤5% (interday). The LOD was 0.23-0.59 µg/mL and the LOQ was 0.71-1.78 µg/mL for each of the drugs analyzed. The method was capable of detecting and quantifying each drug in a mixture with good resolution and a total run time of less than 5 min. Herein, we report an efficient and rapid analytical method for the simultaneous detection of multiple PPIs in a mixture.

Development and validation of HPLC-DAD method for the simultaneous determination of amoxicillin, metronidazole and rabeprazole sodium. Application to spiked simulated intestinal fluid samples.

This work deals with the development, validation and application of an HPLC-DAD method for the determination of a ternary mixture containing amoxicillin (AX), metronidazole (MZ) and the proton pump inhibitor rabeprazole sodium (RB). This triple therapy is used for treatment of Helicobacter pylori infection. Effective chromatographic separation between the three drugs was achieved using Thermo Hypersil BDS-C8 (4.6×250mm, 5µm particle size) column and a mobile phase composed of phosphate buffer pH 7 and acetonitrile (70: 30, by volume). The mobile phase was pumped isocratically at a flow rate of 1 mL/min. Quantification of the analytes was based on measuring their peak areas at 230nm for both AX and RB, and at 319nm for MZ. AX, MZ and RB eluted at retention times 2.36, 3.55 and 8.72min respectively. The reliability and analytical performance of the proposed HPLC procedure were statistically validated with respect to linearity, ranges, precision, accuracy, selectivity, robustness, detection and quantification limits. The linear dynamic ranges were 25-250, 25-250 and 5-50µg/mL for AX, MZ and RB respectively with correlation coefficients>0.9998. The validated method was successfully applied to the analysis of several laboratory-prepared mixtures as well as simulated intestinal fluid samples spiked with the three drugs.

Analytical quality by design-based development of a capillary electrophoresis method for Omeprazole impurity profiling.

Omeprazole (OME) is a proton pump inhibitor used to treat gastroesophageal reflux disease associated conditions. The current study presents an Analytical Quality by Design-based approach for the development of a CE method for OME impurity profiling. The scouting experiments suggested the selection of solvent modified Micellar ElectroKinetic Chromatography operative mode using a pseudostationary phase composed of sodium dodecyl sulfate (SDS) micelles and n-butanol as organic modifier in borate buffer. A symmetric three-level screening matrix 37//16 was used to evaluate the effect of Critical Method Parameters, including Background Electrolyte composition and instrumental settings, on Critical Method Attributes (critical resolution values, OME peak width and analysis time). The analytical procedure was optimized using Response Surface Methodology through a Central Composite Orthogonal Design. Risk of failure maps made it possible to define the Method Operable Design Region, within which the following optimized conditions were selected: 72 mM borate buffer pH 10.0, 96 mM SDS, 1.45 %v/v n-butanol, capillary temperature 21 °C, applied voltage 25 kV. The method was validated according to ICH guidelines and robustness was evaluated using a Plackett-Burman design. The developed procedure enables the simultaneous determination of OME and seven related impurities, and has been successfully applied to the analysis of pharmaceutical formulations.

Characterization of a novel potassium-competitive acid blocker of the gastric H,K-ATPase, 1-[5-(2-fluorophenyl)-1-(pyridin-3-ylsulfonyl)-1H-pyrrol-3-yl]-N-methylmethanamine monofumarate (TAK-438).

Inhibition of the gastric H,K-ATPase by the potassium-competitive acid blocker (P-CAB) 1-[5-(2-fluorophenyl)-1-(pyridin-3-ylsulfonyl)-1H-pyrrol-3-yl]-N-methylmethanamine (TAK-438), is strictly K(+)-competitive with a K(i) of 10 nM at pH 7. In contrast to previous P-CABs, this structure has a point positive charge (pK(a) 9.06) allowing for greater accumulation in parietal cells compared with previous P-CABs [e.g., (8-benzyloxy-2-methyl-imidazo(1,2-a)pyridin-3-yl)acetonitrile (SCH28080), pK(a) 5.6]. The dissociation rate of the compound from the isolated ATPase is slower than other P-CABs, with the t(1/2) being 7.5 h in 20 mM KCl at pH 7. The stoichiometry of binding of TAK-438 to the H,K-ATPase is 2.2 nmol/mg in the presence of Mg-ATP, vanadate, or MgP(i). However, TAK-438 also binds enzyme at 1.3 nmol/mg in the absence of Mg(2+). Modeling of the H,K-ATPase to the homologous Na,K-ATPase predicts a close approach and hydrogen bonding between the positively charged N-methylamino group and the negatively charged Glu795 in the K(+)-binding site in contrast to the planar diffuse positive charge of previous P-CABs. This probably accounts for the slow dissociation and high affinity. The model also predicts hydrogen bonding between the hydroxyl of Tyr799 and the oxygens of the sulfonyl group of TAK-438. A Tyr799Phe mutation resulted in a 3-fold increase of the dissociation rate, showing that this hydrogen bonding also contributes to the slow dissociation rate. Hence, this K(+)-competitive inhibitor of the gastric H,K-ATPase should provide longer-lasting inhibition of gastric acid secretion compared with previous drugs of this class.

Effect of the aqueous extract of entandrophragma utile bark on gastric acid secretion in ghosh and schild rat preparations.

AIMS AND OBJECTIVES: The reduction of aggressive factors such as gastric acid is considered a key target of gastrointestinal protection. We investigated the antisecretory effect of the aqueous bark extract of E. utile, a Nigerian traditional medicinal preparation used for ulcers. METHODS: Male rats were anesthetized and cannulated for intragastric perfusion of saline and test agents as well as for infusion of histamine into the jugular vein. Gastric effluents were collected every 30 min and 10 ml aliquots were titrated against 0.01 N NaOH using phenol red indicator. Gastric acidity was deduced from titre values. Histamine in saline was infused for 2 h at a rate of 1 x 10(-4) g kg-1 min -1 to stimulate acid secretion. In one set of animals, cimetidine in saline was simultaneously perfused intragastrically for 2 h at the rate of 2.5 x 10(-3) g kg(-1) h(-1). Similarly, rats in other sets were simultaneously perfused intragastrically with either the aqueous fresh bark extract of E.utile or the decolorized extract for 2 h at a rate of 1.5 x 10(-3) g kg(-1) h(-1). The extract was also perfused in rats that had established peak gastric acid output with prior infusion of histamine. RESULTS: Mean basal acid output per 0.5 h was 20.2 ± 1.9 mEq. Peak measurement fluctuated within a range of 114 - 117 mEq 0.5h(-1) and was maintained for more than 5 h. Cimetidine or E. utile prevented the rise to peak output that histamine produces. Using the 2-tailed paired t-test, the inhibitory effects of either cimetidine or E. utile was significant (p<0.05) at 60 min. E. utile significantly caused greater inhibition of histamine stimulated gastric acid output than cimetidine at 120 min (p<0.05). When the extract was given after establishment of peak output, the gastric acidity dramatically fell to below the basal level. CONCLUSION: The aqueous bark extract of E. utile contains one or more active component(s) that can be developed as antisecretory medication for hypersecretory states or for protection of the compromised gastrointestinal mucosa.

Ultra-fast gradient LC method for omeprazole analysis using a monolithic column: assay development, validation, and application to the quality control of omeprazole enteric-coated pellets.

A method was optimized for the analysis of omeprazole (OMZ) by ultra-high speed LC with diode array detection using a monolithic Chromolith Fast Gradient RP 18 endcapped column (50 x 2.0 mm id). The analyses were performed at 30 degrees C using a mobile phase consisting of 0.15% (v/v) trifluoroacetic acid (TFA) in water (solvent A) and 0.15% (v/v) TFA in acetonitrile (solvent B) under a linear gradient of 5 to 90% B in 1 min at a flow rate of 1.0 mL/min and detection at 220 nm. Under these conditions, OMZ retention time was approximately 0.74 min. Validation parameters, such as selectivity, linearity, precision, accuracy, and robustness, showed results within the acceptable criteria. The method developed was successfully applied to OMZ enteric-coated pellets, showing that this assay can be used in the pharmaceutical industry for routine QC analysis. Moreover, the analytical conditions established allow for the simultaneous analysis of OMZ metabolites, 5-hydroxyomeprazole and omeprazole sulfone, in the same run, showing that this method can be extended to other matrixes with adequate procedures for sample preparation.

High-performance liquid chromatographic determination of pantoprazole and its main impurities in pharmaceuticals.

An RP-HPLC method for simultaneous separation and quantification of pantoprazole and its five main impurities in pharmaceutical formulations was developed and validated. The separation was accomplished on a Zorbax Eclipse XDB C18 column (5 microm particle size, 150 x 4.6 mm id) using a gradient with mobile phase A [buffer-acetonitrile (70 + 30, v/v)], and mobile phase B [buffer-acetonitrile (30 + 70, v/v)]. The buffer was 0.01 M ammonium acetate solution with addition of 1 mL triethylamine/L of the solution, adjusted to pH 4.5 with orthophosphoric acid. The eluent flow rate was 1 mL/min, the temperature of the column was 30 degrees C, and the eluate was monitored at 290 nm. Linearity (r = 0.999), recovery (97.6-105.8%), RSD (0.55-1.90%), and LOQ (0.099-1.48 microg/mL) were evaluated and found to be satisfactory. The proposed method can be used for simultaneous identification and quantification of the analyzed compounds in pharmaceutical formulations.

Simultaneous Quantitative Analysis of Six Proton-Pump Inhibitors with a Single Marker and Evaluation of Stability of Investigated Drugs in Polypropylene Syringes for Continuous Infusion Use.

OBJECTIVE: We developed and validated a simple, convenient and reproducible method for simultaneous estimation of six proton-pump inhibitors (PPIs), omeprazole (OPZ), esomeprazole (EOPZ), lansoprazole (LPZ), pantoprazole (PPZ), rabeprazole (RPZ) and ilaprazole (IPZ) in pharmaceutical dosage forms by a single marker. Meanwhile, the stability of the cited PPIs in 0.9% sodium chloride injection stored in polypropylene syringes up to 48 hours for continuous infusion use was investigated. MATERIALS AND METHODS: The chromatographic separation was achieved on an InterSustain® C18 column (150 × 4.6 mm, 5 µm). The isocratic mobile phase made up of 0.05 M potassium dihydrogen phosphate buffer (pH 4.0): acetonitrile (65:35, v/v) was pumped through the column at a temperature maintained at 30°C and a flow rate of 1.0 mL/min. The relative retention time, UV spectral similarity and relative correction factors between OPZ and the other five PPIs were calculated and investigated using the quantitative analysis of multi-components with a single marker (QAMS) method. The stability study examined physical parameters, pH values and drug concentrations of the PPIs mixtures. RESULTS: Under these conditions, all cited PPIs were separated simultaneously at a retention time of 6.0, 7.3, 7.3, 9.9, 12.5 and 13.9 min for RPZ, OPZ, EOPZ, IPZ, PPZ and LPZ, respectively, with a total run time less than 20.0 min. Comparative analysis results indicated that there were no significant differences observed between the QAMS method and the external standard method. The percentage of initial concentration of each PPI gradually decreased during the storage time. CONCLUSION: The proposed method, which is selective, economical and accurate, was applied successfully for determination of the cited PPIs in their respective pharmaceutical dosage forms. Admixtures of OPZ, EOPZ, PPZ, IPZ in 0.9% sodium chloride injection were stable for 24 hours and LPZ, RPZ in 0.9% sodium chloride injection were stable for 8 hours in polypropylene syringes.

Three-Dimensional Imaging with Infrared Matrix-Assisted Laser Desorption Electrospray Ionization Mass Spectrometry.

Mass spectrometry imaging as a field has pushed its frontiers to three dimensions. Most three-dimensional mass spectrometry imaging (3D MSI) approaches require serial sectioning that results in a loss of biological information between analyzed slices and difficulty in reconstruction of 3D images. In this contribution, infrared matrix-assisted laser desorption electrospray ionization (IR-MALDESI) was demonstrated to be applicable for 3D MSI that does not require sectioning because IR laser ablates material on a micrometer scale. A commercially available over-the-counter pharmaceutical was used as a model to demonstrate the feasibility of IR-MALDESI for 3D MSI. Depth resolution (i.e., z-resolution) as a function of laser energy levels and density of ablated material was investigated. The best achievable depth resolution from a pill was 2.3 µm at 0.3 mJ/pulse. 2D and 3D MSI were performed on the tablet to show the distribution of pill-specific molecules. A 3D MSI analysis on a region of interest of 15 × 15 voxels across 50 layers was performed. Our results demonstrate that IR-MALDESI is feasible with 3D MSI on a pill, and future work will be focused on analyses of biological tissues.

High-performance thin-layer chromatographic determination of rabeprazole sodium and domperidone in combined dosage form.

A new, simple, high-performance thin-layer chromatographic method for determination of rabeprazole sodium (RAB) and domperidone (DOM) in combined tablet dosage form has been developed and validated. The mobile phase was toluene-acetone-methanol (4.5 + 4.5 + 0.5, v/v/v) with UV detection at 285 nm. The retention factors for RAB and DOM were found to be 0.53 +/- 0.12 and 0.32 +/- 0.20. The method was validated with respect to linearity, accuracy, precision, and robustness. Beer's law was obeyed in the concentration range of 50-800 ng/band for both RAB and DOM. The method has been successfully applied for the analysis of drugs in a pharmaceutical formulation.

Application of a stability-indicating thin-layer chromatographic method to the determination of tenatoprazole in pharmaceutical dosage forms.

A sensitive, selective, precise, and stability-indicating thin-layer chromatographic (TLC) method was developed and validated for the determination of tenatoprazole both as a bulk drug and in formulation. The method uses TLC aluminum plates precoated with Silica Gel 60F-254 as the stationary phase and the solvent system toluene-ethyl acetate-methanol (6 + 4 + 1, v/v/v). This system gave compact spots for tenatoprazole (Rf value of 0.34 +/- 0.02). Tenatoprazole was subjected to acid and alkali hydrolysis, oxidation, and photodegradation. The peaks of the degradation products were well-resolved from that of the pure drug and had significantly different Rf values. Densitometric analysis of tenatoprazole was performed in the absorbance mode at 306 nm. The linear regression analysis data for the calibration plots showed a good linear relationship over the concentration range of 100-1500 ng/spot. The mean values of the correlation coefficient, slope, and intercept were 0.9989 +/- 1.42, 10.27 +/- 0.965, and 4894.2 +/- 1.24, respectively. The method was validated for precision, robustness, and recovery. The limit of detection and limit of quantitation were 50 and 100 ng/spot, respectively. Statistical analysis showed that the method is repeatable and selective for estimation of tenatoprazole. Because the method can separate the drug from its degradation products, it can be used to monitor stability.

A rapid Fourier transform infrared spectroscopic method for analysis of certain proton pump inhibitors in binary and ternary mixtures.

A simple and non-destructive FTIR method was used to determine certain proton pump inhibitors (PPIs) in binary and ternary mixtures. Proton pump inhibitors (PPIs); omeprazole (OMZ), esomeprazole (EZM), lansoprazole (LAN), pantoprazole sodium (PAN sodium) and rabeprazole sodium (RAB sodium) in binary mixture with domperidone (DOM) and ternary mixture of OMZ, clarithromycin (CLM) and tinidazole (TNZ) were determined in the solid-state by FTIR spectroscopy for the first time. The method was validated according to ICH-guidelines where linearity was ranged from 20 to 850µg/g and 20-360µg/g for PPIs and DOM, respectively in binary mixtures and 10-400, 100-8000 and 150-14,000µg/g for OMZ, CLM and TNZ, respectively. Limits of detection were found to be 6-100 and 9-100µg/g for PPIs and DOM, respectively and 4, 40 and 50µg/g for OMZ, CLM and TNZ, respectively. The method was applied successfully for determination of the cited drugs in their respective pharmaceutical dosage forms.

In vitro comparative quality evaluation of different brands of esomeprazole tablets available in selected community pharmacies in Dhaka, Bangladesh.

OBJECTIVE: Esomeprazole is the S-isomer of omeprazole, used to treat gastro esophageal reflux disease. It is one of the widely manufactured and marketed drugs by many pharmaceutical companies in Bangladesh. The aim of the study is to compare the different physical parameters including hardness, friability, diameter, thickness, disintegration time, dissolution test and assay for quality evaluation and characterization of tablets of five different brands of Bangladeshi pharmaceutical company. The specified compendial method was followed for their evaluation test. RESULTS: Esomeprazole Mg tablets are enteric coated tablet, there was no disintegration for any brand occurred in 0.1 N HCl after 2 h and all tablets were disintegrated within 19.93 ± 0.04 to 29.05 ± 0.14 min in phosphate buffer (pH 6.8). Weight variation and Hardness were between 1.01 ± 0.29 to 2.01 ± 0.14% and 5.32 ± 0.06 to 7.12 ± 0.12 kgf respectively. Medicine released after 2 h in 0.1 N HCl were varied from 2.55 ± 0.24 to 4.47 ± 0.31% which was less than 10% and in phosphate buffer (pH 6.8) the percentage of medicine release were between 100.9 and 105.9% after 60 min. In case of assay the results of all brands were between 95.28 ± 0.08 and 99.40 ± 0.11%. The obtained results of all parameters were complied with pharmacopoeial limit. So from this study we can conclude that products of esomeprazole available in Bangladeshi pharmaceutical market meet the quality parameter to satisfy therapeutic efficacy.

Development of a stability- indicating HPLC method for simultaneous determination of ten related substances in vonoprazan fumarate drug substance.

Vonoprazan fumarate is a novel potassium-competitive acid blocker for the treatment of acid-related diseases. In the present study, a simple, fast, and economic reversed-phase liquid chromatography (LC) method was developed for the analysis of ten related substances (raw materials, by-products and degradants) in vonoprazan fumarate. The optimized separation was performed on a Phenomenex Kinetex EVO C18 (250mm×4.6mm, 5.0µm) column. The mobile phase consisted of (A) 0.03M sodium phosphate buffer (pH adjusted to 6.5) - methanol - acetonitrile (72:25:3, v/v/v) and (B) 0.03M sodium phosphate buffer (pH adjusted to 6.5) - acetonitrile (30:70, v/v). Detection of the analytes was conducted at 230nm using a UV detector. The stability-indicating ability of this method was demonstrated by carrying out forced degradation studies. Vonoprazan underwent significant degradation when subjected to alkaline and oxidative stress conditions, while the drug proved to be stable to acidic, thermal and photolytic degradation. The degradants did not interfere with the detection of vonoprazan fumarate and its impurities. The performance of this method was validated in accordance to the regulatory guidelines recommended by the International Conference on Harmonisation (ICH) and this validation included specificity, linearity, limit of detection (LOD), limit of quantification (LOQ), accuracy, precision and robustness. The method proposed in this paper could be applied for process development as well as quality assurance of vonoprazan in bulk drug, since no monograph is available in official compendia.

Determination of rabeprazole enantiomers in commercial tablets using immobilized cellulose-based stationary phase.

Rabeprazole is one of the latest proton-pump inhibitors used for treatment of several gastrointestinal disorders. For therapeutic applications, rabeprazole has been administered as a mixture of R-(+) and S-(-) enantiomers. Owing to pharmacological and toxicological differences between stereoisomers, chiral recognition has now become an integral part of drug research and development. A simple and rapid liquid chromatographic method for enantioselective separation and determination of R-(+) and S-(-) enantiomers of rabeprazole in bulk drug and pharmaceutical formulations was developed. Chiralpak IC (150 × 4.6 mm, 5 µm) column and µmobile phase containing hexane:ethanol:ethylenediamine (30:70:0.05 v/v) in an isocratic mode yielded baseline separation with resolution greater than 6.0 at 35 °C. Effects of additives and n-hexane were evaluated. Optimized condition was validated as per ICH guidelines. The method has good linearity, high sensitivity with LOD was 0.01 µg/mL and LOQ was 0.03 µg/mL for both enantiomers. Intra-day precision varied between 0.44 and 1.79% for S-(-) enantiomer, 0.65 and 1.97% for R-(+) enantiomer. Relative standard deviations of inter-day precision were less than 1.81% for both enantiomers. The percentage recovery for both enantiomers of rabeprazole ranged between 99.81 and 101.95%, 98.82 and 101.36% in material and tablets, respectively. The method was successfully applied to determine content of each enantiomer in commercial tablets.

Determination of S-(-)-lansoprazole in dexlansoprazole preparation by capillary zone electrophoresis.

Capillary zone electrophoresis was successfully applied to the enantiomeric purity determination of dexlansoprazole using sulfobutyl ether-ß-cyclodextrin and methyl-ß-cyclodextrin as chiral selectors. Separations were carried out in a 50 µm, 64/56 cm fused-silica capillary. The optimized conditions included 90 mM phosphate buffer, pH 6.0, containing 30 mM sulfobutyl ether-ß-cyclodextrin, 20 mM methyl-ß-cyclodextrin as background electrolyte, an applied voltage of 25 kV and a temperature of 16 °C, detection was at 280 nm. The assay was validated for the S-(-)-lansoprazole in the range of 0.2-1.0%. The limit of detection was 0.07%, the limit of quantitation was 0.20%, relative to a total concentration of 4.0 mg mL-1. Intra-day precision varied between 1.72 and 2.07%. Relative standard deviations of inter-day precision ranged between 1.62 and 1.96% for peak area ratio. The assay was applied for the determination of the chiral purity of dexlansoprazole capsules. Recovery in capsules was ranged between 101.7 and 103.1%.