New LC-MS-MS Method for Quantitative Analysis of Adefovir, and Its Use for Pharmacokinetic Studies in Healthy Chinese Volunteers

A rapid and sensitive liquid chromatographic-tandem mass spectrometric method for analysis of adefovir in human plasma has been developed and validated. After protein precipitation and evaporation, 10 μL supernatant was injected for reversed-phase LC separation. Adefovir and the internal standard (acyclovir) were monitored in selected reaction monitoring (SRM) mode at m/z 274.10 → 256.00 and 226.10 → 152.00, respectively. The calibration plot was linear over the concentration range 0.5-100 ng mL⁻¹, and correlation coefficients were >0.999. Mean intra-day and inter-day accuracy ranged from 89.43 to 93.20% and from 91.40 to 95.57%, respectively, and mean intra-day and inter-day precision was between 2.40 and 7.66% and between 5.60 and 10.47%, respectively. The method was successfully applied to a Phase I pharmacokinetic study of adefovir after oral administration of adefovir dipivoxil capsules at doses of 5, 10, and 20 mg to twenty-four healthy Chinese volunteers.