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.
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.
Uno
Tsukasa
T
Department of Pharmacy, Hirosaki University Hospital, Hirosaki 036-8563, Japan. uno-hki@umin.ac.jp
Yasui-Furukori
Norio
N
Shimizu
Mikiko
M
Sugawara
Kazunobu
K
Tateishi
Tomonori
T
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000284:Administration, Oral; D000328:Adult; D019540:Area Under Curve; D001562:Benzimidazoles / Q000097:blood* / Q000378:metabolism / Q000493:pharmacokinetics; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D005260:Female; D006207:Half-Life; D006801:Humans; D008297:Male; D009853:Omeprazole / Q000031:analogs & derivatives* / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics; D064750:Rabeprazole; D015203:Reproducibility of Results; D013440:Sulfides / Q000097:blood* / Q000737:chemistry
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D001562:Benzimidazoles; D013440:Sulfides; D064750:Rabeprazole; D009853:Omeprazole