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

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 μg·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.