关键词: 阿帕替尼, 液质联用法, 血药浓度, 药物动力学

Abstract:

AIM: To establish a rapid, accurate liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the determination of apatinib in tumor patients and apply this method to analyze the clinical samples. METHODS: Sorafenib was employed as the internal standard. The analyte and internal standard were extracted from plasma by protein precipitation with acetonitrile and separated on Eclipse Plus C18 column (2.1 mm×100 mm, 3.5 μm) , mobile phase consisted of acetonitrile-10 mmol/L ammonium acetate (85∶15, V/V, containing 0.1% formic acid) at the flow rate of 0.25 mL/min. Electrospray ionization (ESI) source was applied and operated in the positive multiple reaction monitoring (MRM) mode.The MS/MS ion transitions monitored were m/z 398.1→m/z 212.0 and m/z 465.3→m/z 270.1 for apatinib and internal standard, respectively. After methodology validation, this method was applied for the clinical analysis of apatinib in plasma from tumor patients.RESULTS:Chromatograms showed no endogenous interfering peaks with blank samples. The standard curves were demonstrated to be liner in the range of 2.0-2 000 μg/L (r=0.996 8). The RSD of inter-day (n=5) and intra-day (n=3) for four different concentration levels were less than 15%, The average recoveries were between 78.0% and 87.8%.The internal standard normalized matrix effect 92.4% and 107.3%. CONCLUSION: The method is specific, sensitive and suitable for clinical determination of apatinib in tumor patients plasma efficiently.

Key words: apatinib, LC-MS/MS, plasma concentration, pharmacokinetics