关键词: 液质联用, 替诺福韦, 药代动力学, 血浆

Abstract:

In the present study, we developed and validated a selective, specific and sensitive liquid chromatography-electrospray ionization mass spectrometry (LC-ESI-MS/MS) method for the determination of tenofovir in human plasma. Entecavir was used as an internal standard, and plasma samples were prepared by solid-phase extraction performed on Phenomenex Strata cartridges (30 mg). The mobile phase consisted of 10 mM ammonium acetate in water and methanol (60:40, v/v). The chromatographic separation was performed isocratically on a Phenomenex C₁₈ (4.6 mm×150 mm, 5 μm), and analytes were analyzed in multiple reaction monitoring (MRM) mode with positive electrospray ionization (ESI) interface using the respective [M+H]⁺ ions, m/z 288.2→m/z 176.1 for tenofovir and m/z 278.1→m/z 152 for entecavir. The calibration curve (r² = 0.9962) of tenofovir was established within the range of 4.096–1000 μg/L. The intra- and inter-day precisions were less than 10%. This validated method was successfully applied to a pharmacokinetic study in 12 healthy Chinese volunteers after the oral administration of tenofovir disoproxil fumarate.

Key words: LC-ESI-MS/MS, Tenofovir, Pharmacokinetic, Plasma