title: 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.
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 C8 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.
authors.affiliation: National Beijing Center for Drug Safety Evaluation and Research, Beijing Institute of Pharmacology and Toxicology, Academy of Military Medical Sciences, 27 Taiping Road, Haidian District, Beijing, 100850, People's Republic of China.|Pharmacy Department of 371 Hospital, 210 Wenhua Road, Hongqi District, Xinxiang City, Henan Province, 453000, People's Republic of China.
authors.forename: Feng
authors.initials: F
authors.lastname: Liang
authors.affiliation: National Beijing Center for Drug Safety Evaluation and Research, Beijing Institute of Pharmacology and Toxicology, Academy of Military Medical Sciences, 27 Taiping Road, Haidian District, Beijing, 100850, People's Republic of China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Kong
authors.affiliation: Gloria Pharmaceuticals Co., Ltd, No.28 Building, Ronghui Garden, Yuhua Road, Konggang Airport Development Zone B, Shunyi District, Beijing, 101318, People's Republic of China.
authors.forename: Yongqi
authors.initials: Y
authors.lastname: Guo
authors.affiliation: Gloria Pharmaceuticals Co., Ltd, No.28 Building, Ronghui Garden, Yuhua Road, Konggang Airport Development Zone B, Shunyi District, Beijing, 101318, People's Republic of China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Gloria Pharmaceuticals Co., Ltd, No.28 Building, Ronghui Garden, Yuhua Road, Konggang Airport Development Zone B, Shunyi District, Beijing, 101318, People's Republic of China.
authors.forename: Dejie
authors.initials: D
authors.lastname: Sun
authors.affiliation: Gloria Pharmaceuticals Co., Ltd, No.28 Building, Ronghui Garden, Yuhua Road, Konggang Airport Development Zone B, Shunyi District, Beijing, 101318, People's Republic of China.
authors.forename: Shi
authors.initials: S
authors.lastname: Liu
authors.affiliation: Gloria Pharmaceuticals Co., Ltd, No.28 Building, Ronghui Garden, Yuhua Road, Konggang Airport Development Zone B, Shunyi District, Beijing, 101318, People's Republic of China.
authors.forename: Jinling
authors.initials: J
authors.lastname: Cai
authors.affiliation: National Beijing Center for Drug Safety Evaluation and Research, Beijing Institute of Pharmacology and Toxicology, Academy of Military Medical Sciences, 27 Taiping Road, Haidian District, Beijing, 100850, People's Republic of China.
authors.forename: Yongbiao
authors.initials: Y
authors.lastname: Guan
authors.affiliation: National Beijing Center for Drug Safety Evaluation and Research, Beijing Institute of Pharmacology and Toxicology, Academy of Military Medical Sciences, 27 Taiping Road, Haidian District, Beijing, 100850, People's Republic of China.
authors.forename: Rigao
authors.initials: R
authors.lastname: Ding
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000097:blood* / Q000378:metabolism; D005260:Female; D000882:Haplorhini / Q000097:blood*; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000097:blood / Q000188:drug therapy / Q000378:metabolism; D057230:Limit of Detection; D008297:Male; D047428:Protein Kinase Inhibitors / Q000097:blood* / Q000378:metabolism; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors
keywords: LC/MS/MS; meditinib; monkey plasma; novel tyrosine kinase inhibitor; pharmacokinetics