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


CONCLUSIONS
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.
Zhao
Li-yan
LY
Laboratory of Drug Metabolism and Pharmacokinetics, Shenyang Pharmaceutical University, Shenyang 110016, China.
Chen
Xiao-yan
XY
Zhang
Yong
Y
Yang
Han-yu
HY
Zhong
Da-fang
DF
D000225:Adenine / Q000031:analogs & derivatives* / Q000097:blood* / Q000493:pharmacokinetics; D000818:Animals; D000998:Antiviral Agents / Q000097:blood* / Q000493:pharmacokinetics; D001711:Biotransformation; D002853:Chromatography, Liquid; D008253:Macaca mulatta; D063065:Organophosphonates; D021241:Spectrometry, Mass, Electrospray Ionization
D000998:Antiviral Agents; D063065:Organophosphonates; C053001:adefovir; D000225:Adenine; C106812:adefovir dipivoxil