Premium
Simultaneous determination of the novel tyrosine kinase inhibitor meditinib and its active metabolite demethylation meditinib in monkey plasma by liquid chromatography–tandem mass spectrometry and its application to pharmacokinetic studies
Author(s) -
Liang Feng,
Kong Qi,
Guo Yongqi,
Wang Yu,
Sun Dejie,
Liu Shi,
Cai Jinling,
Guan Yongbiao,
Ding Rigao
Publication year - 2015
Publication title -
biomedical chromatography
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.4
H-Index - 65
eISSN - 1099-0801
pISSN - 0269-3879
DOI - 10.1002/bmc.3415
Subject(s) - chemistry , chromatography , protein precipitation , formic acid , metabolite , pharmacokinetics , demethylation , liquid chromatography–mass spectrometry , active metabolite , methanol , analyte , mass spectrometry , pharmacology , biochemistry , medicine , gene expression , organic chemistry , dna methylation , gene
Abstract Meditinib (ME) is a novel tyrosine kinase inhibitor used as an antichronic myeloid leukemia drug. A simple, sensitive and specific LC/MS/MS method was developed and validated for the analysis of ME and its metabolite demethylation meditinib (PI) in monkey plasma using naltrexone as the internal standard. Sample preparation involved protein precipitation with methanol. The analysis was carried out on an Agilent C 8 column (3.5 µm, 2.1 × 50 mm). Elution was achieved with a mobile phase gradient varying the proportion of a water solution containing 0.1% formic acid (solvent A) and a 0.1% formic acid in methanol solution (solvent B) at a flow rate of 300 μL/min. The method had a linear calibration curve over the concentration range of 2–1000 ng/mL for ME and 2–1000 ng/mL for PI. The lower limits of quantification of ME and PI were 2 and 2 ng/mL, respectively. The intra‐ and inter‐day precision values were <15% and accuracy values were within ±10.0%. The mean recoveries of ME and PI from plasma were >85%. The assay has been successfully used for pharmacokinetic evaluation of ME and PI using the monkey as an animal model, and those data are reported for the first time. Copyright © 2015 John Wiley & Sons, Ltd.