Determination of Adefovir by LC-ESI-MS-MS and Its Application to a Pharmacokinetic Study in Healthy Chinese Volunteers

A selective and sensitive high-performance liquid chromatography-electrospray-tandem mass spectrometry method (HPLC-ESI-MS-MS) has been developed for the determination of adefovir in human plasma using adenine (PMPA) as an internal standard. After protein precipitation with methanol, the plasma sample was separated by HPLC on a reversed-phase XTerra MS/MS C(18) column (100 mm x 2.1 mm i.d., 3.5 mm) with a mobile phase of methanol-water (20:80, v/v). Standard curves were linear (r(2) = 0.9962) over the concentration range of 0.20-100 ng/mL and had acceptable accuracy and precision. The intra- and inter-batch precisions were within 11.30%. The lower limit of quantification (LLOQ) was 0.20 ng/mL. The validated HPLC-ESI-MS-MS method has been used successfully to study the pharmacokinetics of adefovir in healthy Chinese volunteers. The following pharmacokinetic parameters were elucidated after administering a single dose of 10 mg, 20 mg, and 30 mg of adefovir dipivoxil. Peak plasma concentrations (C(max)) were (26.6 +/- 6.1), (55.7 +/- 16.2), and (70.2 +/- 11.8) ng/mL, respectively; time to C(max) (T(max)) were (1.5 +/- 0.6), (1.6 +/- 0.7), and (1.8 +/- 0.6) h, respectively; the area under the plasma concentration versus time curve from time 0 h to 36 h (AUC(0-36)) were (184.5 +/- 25.2), (379.3 +/- 61.8) and (556.5 +/- 86.7) ng/mL, respectively; mean residence times (MRT) were (8.9 +/- 0.9), (9.0 +/- 1.0), and (8.9 +/- 1.0) h, respectively; and the elimination half-life (t(1/2)) were (8.0 +/- 0.9), (7.5 +/- 0.8), and (7.5 +/- 0.9) h, respectively. The pharmacokinetic parameters can provide some information for clinical medication.