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[Determination of adefovir in monkey plasma by liquid chromatography-tandem mass spectrometry]
Li-yan Zhao1, Xiao-yan Chen, Yong Zhang
1Laboratory of Drug Metabolism and Pharmacokinetics, Shenyang Pharmaceutical University, Shenyang 110016, China.
Aim:
To develop a sensitive and specific liquid chromatography-tandem mass spectrometry (LC/MS/MS) method for the determination of adefovir in monkey plasma.
Methods:
Adefovir 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.
Results:
The 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.
Conclusion:
The 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.