The chiral bioconversion and preclinical pharmacokinetic analysis of (R)‐(+)‐rabeprazole in beagle dogs by HPLC and HPLC‐MS/MS |
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Authors: | Yan‐hui Gao Jia‐xing Xu Zhong‐xue Su Li Song Hong‐xiang Lou |
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Institution: | 1. School of Pharmaceutical Sciences of Shandong University, , Jinan, 250012 China;2. Laboratory Animal Center of Shandong University, , Jinan, 250012 China;3. Department of Hepatobiliary and Pancreatic Surgery, Provincial Hospital affiliated to Shandong University, , Jinan, 250021 China;4. Department of Natural Products Chemistry, Key Laboratory of Chemical Biology of Ministry of Education, Shandong University, , Jinan, 250012 China |
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Abstract: | In order to accurately investigate the preclinical pharmacokinetics of (R)‐(+)‐rabeprazole sodium injection, a reliable high‐performance liquid chromatography (HPLC) method was developed using a Chiral‐AGP column to prove that there is no chiral bioconversion of (R)‐(+)‐rabeprazole to (S)‐(?)‐rabeprazole in beagle dogs after single intravenous administration of (R)‐(+)‐rabeprazole sodium injection. An HPLC–tandem mass spectrometry (HPLC‐MS/MS) method for analysis of (R)‐(+)‐rabeprazole was developed and validated, and used to acquire the pharmacokinetic parameters in beagle dogs. (R)‐(+)‐Rabeprazole and internal standard omeprazole were extracted from plasma samples by protein precipitation and separated on a C18 column using methanol–5 mm ammonium acetate as mobile phase. Detection was performed using a turbo‐spray ionization source and mass spectrometric positive multi‐reaction monitoring mode. The linear relationship was achieved in the range from 2.5 to 5000 ng/mL. The method also afforded satisfactory results in terms of sensitivity, specificity, precision, accuracy and recovery as well as the stability of the analyte under various conditions, and was successfully applied to a preclinical pharmacokinetic study in beagle dogs after single intravenous administrations of (R)‐(+)‐rabeprazole sodium injection at 0.33, 2 and 6 mg/kg. Copyright © 2013 John Wiley & Sons, Ltd. |
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Keywords: | (R)‐(+)‐rabeprazole (S)‐(− )‐rabeprazole chiral bioconversion pharmacokinetic HPLC‐MS/MS |
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