Acta Pharmaceutica Sinica 2003;38(2):120-123

Determination of adefovir in monkey plasma by liquid chromatography-tandem mass spectrometry.

Li-yan ZHAO 1 ; Xiao-yan CHEN ; Yong ZHANG ; Han-yu YANG ; Da-fang ZHONG

Affiliations

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Country

China

Language

Chinese

Abstract

AIMTo develop a sensitive and specific liquid chromatography-tandem mass spectrometry (LC/MS/MS) method for the determination of adefovir in monkey plasma.

METHODSAdefovir and internal standard 9-(3-phosphonylmethoxypropyl) adenine were isolated from plasma by protein precipitation with methanol, then chromatographed by using a Diamonsil C18 column. The mobile phase consisted of methanol-water-formic acid (20:80:1). Electrospray ionization (ESI) source was applied and operated in the positive ion mode. Selected reaction monitoring (SRM) mode with the transitions of m/z 274-->m/z 162 and m/z 288-->m/z 176 were used to quantify adefovir and the internal standard, respectively.

RESULTSThe linear calibration curve was obtained in the concentration range of 0.02-4.00 mg.L-1. The lower limit of quantitation was 20 micrograms.L-1. The inter- and intra-day precision (RSD) was less than 5.8%, and the accuracy (relative error) was within +/- 4.5%. The method was successfully used in a pharmacokinetic study of adefovir dipivoxil in monkeys.

CONCLUSIONThe method is proved to be suitable for pre-clinical investigation of adefovir dipivoxil pharmacokinetics, which offers advantages of specificity and simple sample preparation compared with the previously reported methods.