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A rapid and selective UPLC-MS/MS assay for accurate analysis of apatinib in rat plasma and its application to a pharmacokinetic study

Author(s):

Jinglin Gao, Zhangying Feng, Huan Ren, Mengdi Yu, Haidong Wang and Mingxia Wang*  

Abstract:


Objective: Apatinib, a novel small-molecule tyrosine kinase inhibitor (TKI), is under development to treat advanced gastric cancer. As to pharmacokinetic evaluation and routine drug monitoring of apatinib, a quantitative ultra-performance liquid chromatography coupled to tandem mass spectrometry (UPLC-MS/MS) method in rat plasma was developed with tinidazole used as an internal standard (IS).

Method: Protein precipitation (PPT) was selected as a sample pre-treatment method to extract apatinib. Then chromatography was performed on a Kinetex C8 column (2.1×100 mm, 2.6 μm) using a constant mobile phase including 0.2% formic acid and 10 mM ammonium acetate in water and methanol (30:70, v/v) with a gradient flow rate from 0.2 mL/min to 0.4 mL/min. Only 4.5 min was for a total chromatographic analysis. Mass spectrometric detection was carried on positive electrospray ionization (ESI+) mode with multiple-reaction monitoring (MRM).

Results: Standard calibration curve showed good linearity in 2-1000 ng/mL with the correlation coefficient (R2) > 0.99. The lower limit of quantitation (LLOQ) was 2 ng/mL. The precision, accuracy, extraction recovery, matrix effect, stability and carryover were all within acceptable range.

Conclusion: This method was simple, accurate, selective and successfully used for a pharmacokinetic study following seven rats orally administrated a single of 60 mg/kg apatinib.

Keywords:

apatinib, UPLC-MS/MS, rat plasma, pharmacokinetics, protein precipitation, method development with validation

Affiliation:

Department of Clinical Pharmacology, Fourth Hospital of Hebei Medical University 12 Jiankang Rd, Shijiazhuang, 050011, Department of Clinical Pharmacology, Fourth Hospital of Hebei Medical University 12 Jiankang Rd, Shijiazhuang, 050011, Department of Clinical Pharmacology, Fourth Hospital of Hebei Medical University 12 Jiankang Rd, Shijiazhuang, 050011, Department of Clinical Pharmacology, Fourth Hospital of Hebei Medical University 12 Jiankang Rd, Shijiazhuang, 050011, Department of Clinical Pharmacology, Fourth Hospital of Hebei Medical University 12 Jiankang Rd, Shijiazhuang, 050011, Department of Clinical Pharmacology, Fourth Hospital of Hebei Medical University 12 Jiankang Rd, Shijiazhuang, 050011



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