关键词: 阿西替尼, 液质联用, 裸鼠, 药物动力学

Abstract:

In the present study, a simple, rapid, and sensitive liquid chromatography-tandem mass spectrometric method for the determination of axitinib in nude mouse plasma was developed, validated, and applied to a pharmacokinetic study. Plasma samples were pre-treated by protein precipitation with acetonitrile spiked with erlotinib as an internal standard. The chromatographic separation was accomplished by using a reversed phase C₁₈ column (50 mm×2 mm, 5 μm) with a simple mobile phase system composed of methanol and water (60:40, v/v) at an isocratic flow rate of 0.4 mL/min. The analyte was detected by a triple-quadrupole tandem mass spectrometer via electrospray ionization and multiple reaction monitoring was employed to select both axitinib and erlotinib in the positive ion mode. The calibration curves were linear (r>0.99) ranging from 1 to 1000 ng/mL, and the lowest level of this range was the lower limit of quantification. The intra­ and inter­day precision were 7.7%-12.0%, and the accuracies ranged from 88.6% to 110.4%. This method was successfully applied to a preclinical pharmacokinetic study on female nu/nu nude mice administrated with a single oral dose of axitinib at 120 mg/kg, and the pharmacokinetics was characterized by a one-compartment model with first-order absorption.

Key words: Axitinib, LC-MS/MS, Nude mice, Pharmacokinetics