Determination of a new H(+)-K+ ATPase inhibitor (E3810) and its four metabolites in human plasma by high-performance liquid chromatography.
A method for the simultaneous determination of E3810, 2-[(4-(3-methoxypropoxy)-3-methyl pyridine-2-yl)methyl sulfinyl]-1H-benzimidazole sodium salt and its four metabolites, demethylated-E3810 (DM), demethylated thioether-E3810 (DMTE), sulfone-E3810 (S), and thioether-E3810 (TE), in human plasma by high-performance liquid chromatography (HPLC) with UV absorbance detection has been established. The correlation coefficient for all the standard curves was 0.998 or greater. The quantitation limit was 5 ng/ml for E3810 and 20 ng/ml for each of its four metabolites. The recovery of E3810 and its four metabolites from human plasma was high, being greater than 80% when 100 ng of each substance was added per tube, except for DM (74.1%). The stability of E3810 and its four metabolites was evaluated and the following results were obtained: (1) when samples were centrifuged within 20 min after collection, there was no loss of E3810 or its metabolites; (2) when 100 microliters of a 1% aqueous solution of diethylamine was added within 20 min after plasma isolation, there was no loss of E3810 or its metabolites; and (3) there were no stability problems during storage for a period of 10 months at -20 degrees C.
Department of Clinical Chemistry, Tokyo Research Laboratories, Eisai Co., Ltd., Japan.
H
H
Nakai
Y
Y
Shimamura
T
T
Kanazawa
S
S
Yasuda
M
M
Kayano
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D001562:Benzimidazoles / Q000097:blood* / Q000493:pharmacokinetics; D002851:Chromatography, High Pressure Liquid; D006207:Half-Life; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007202:Indicators and Reagents; D009853:Omeprazole / Q000031:analogs & derivatives; D054328:Proton Pump Inhibitors; D064750:Rabeprazole; D013056:Spectrophotometry, Ultraviolet
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D001562:Benzimidazoles; D007202:Indicators and Reagents; D054328:Proton Pump Inhibitors; D064750:Rabeprazole; D009853:Omeprazole