Determination of rabeprazole and its active metabolite, rabeprazole thioether in human plasma by column-switching high-performance liquid chromatography and its application to pharmacokinetic study.
ABSTRACT A new sensitive column-switching high-performance liquid chromatographic (HPLC) method with ultraviolet detection was developed for the simultaneous determination of rabeprazole, a proton pump inhibitor, and its active metabolite, rabeprazole thioether in human plasma. Rabeprazole, its thioether metabolite and 5-methyl-2-[(4-(3-methoxypropoxy)-3-methyl pyridin-2-yl) methyl sulfinyl]-1H-benzimidazole, as an internal standard were extracted from 1 ml of plasma using diethyl ether-dichloromethane (9:1, v/v) mixture and the extract was injected into a column I (TSK-PW precolumn, 10 microm, 35 mmx4.6mm I.D.) for clean-up and column II (C18 Grand ODS-80TM TS analytical column, 5 microm, 250 mmx4.6 mm I.D.) for separation. The peak was detected with an ultraviolet detector set at a wavelength of 288 nm, and the total time for chromatographic separation was approximately 25 min. Mean absolute recoveries were 78.0 and 88.3% for rabeprazole and rabeprazole thioether, respectively. Intra- and inter-day coefficient variations were less than 6.5 and 4.5% for rabeprazole, 3.6 and 5.3% for rabeprazole thioether, respectively, at the different concentration ranges. The validated concentration ranges of this method were 1-1000 ng/ml for rabeprazole and 3-500 ng/ml for rabeprazole thioether. The limits of quantification were 1 ng/ml for rabeprazole and 3 ng/ml for rabeprazole thioether. The method was suitable for therapeutic drug monitoring and was applied to pharmacokinetic study in human volunteers.
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ABSTRACT: A reversed-phase high-performance liquid chromatographic method was developed and validated for the determination of rabeprazole in pharmaceutical dosage forms. The determination was performed on a Nucleodur column C8 (250×4.6 mm i.d., 5m particle size); the mobile phase consisted of a mixture of 0.1M formic acid and methanol (58:42, v/v), pumped at a flow rate 1.0 mL min−1. The photodiode array detector was operated at 280 nm. The retention times for rabeprazole and pantoprazole, which was used as internal standard, were 5.13 and 11.12 min, respectively. Linearity range (r2 better than 0.999, n=5) was 40-1600 g mL-1 with limit of detection value of 2.56g mL-1. The precision of the method was demonstrated using intra- and inter-day assay RSD values which were less than 2.82%, while the recovery was 100.07-104.54% (n=14). The method was applied in the quality control of commercial tablets and content uniformity test and proved to be suitable for rapid and reliable quality control.Reaserch Journal of Aleppo University. 01/2011; 75.
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ABSTRACT: A simple and rapid liquid chromatography with tandem mass spectrometry method has been developed and validated for the determination of rabeprazole and its two active metabolites, rabeprazole thioether and desmethyl rabeprazole thioether, in human urine using donepezil as the internal standard. The sample preparation procedure involved a simple dilution of urine sample with methanol (1:3, v/v). The chromatographic separation was achieved on a Hedera ODS-2 C18 column using a mixture of methanol/10 mmol/L ammonium acetate solution (containing 0.05% formic acid) (55:45, v/v) as the mobile phase. The method was validated over the concentration ranges of 0.15–100 ng/mL for rabeprazole, 0.30–400 ng/mL for rabeprazole thioether and 0.05–100 ng/mL for desmethyl rabeprazole thioether. The established method was highly sensitive with a lower limit of quantification of 0.15 ng/mL for rabeprazole and 0.30 ng/mL for rabeprazole thioether and 0.05 ng/mL for desmethyl rabeprazole thioether. The intra- and inter-batch precision was less than 4.5% for the low, medium and high quality control samples of all the analytes. The recovery of the analytes was in the range 95.4–99.0%. The method was successfully applied to a urinary excretion profiles after intravenous infusion administration of 20 mg rabeprazole sodium in healthy volunteers.This article is protected by copyright. All rights reservedJournal of Separation Science 05/2014; · 2.59 Impact Factor
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ABSTRACT: Rabeprazole sodium (Aciphex®) is a gastric proton pump inhibitor used for the prevention and treatment of gastric acid–related diseases. During the synthesis of bulk drug of rabeprazole sodium, we have observed metabolites rabeprazole sulfide and rabeprazole sulfone and related substances rabeprazole-N-oxide, rabeprazole sulfone-N-oxide, N-aralkyl rabeprazole, chloro rabeprazole, and methoxy rabeprazole as impurities in the drug substance. The present work describes the synthesis and characterization of these compounds.Synthetic Communications 01/2009; 39(2):278-290. · 1.06 Impact Factor