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.

Tsukasa Uno, Norio Yasui-Furukori, Mikiko Shimizu, Kazunobu Sugawara, Tomonori Tateishi

Department of Pharmacy, Hirosaki University Hospital, Hirosaki 036-8563, Japan. uno-hki@umin.ac.jp

Journal of chromatography. B, Analytical technologies in the biomedical and life sciences 2005 Sep 25

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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.

Citation

Tsukasa Uno, Norio Yasui-Furukori, Mikiko Shimizu, Kazunobu Sugawara, Tomonori Tateishi. 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. Journal of chromatography. B, Analytical technologies in the biomedical and life sciences. 2005 Sep 25;824(1-2):238-43