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Development of a rapid and sensitive UPLC‐MS/MS assay for the determination of TM‐2 in beagle dog plasma and its application to a pharmacokinetic study
Author(s) -
Lin Hongli,
Zhao Yunli,
Men Lei,
Yang Mingjing,
Liu Hui,
Shao Yanjie,
Wang Pei,
Tang Xing,
Yu Zhiguo
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.3246
Subject(s) - chemistry , chromatography , beagle , electrospray ionization , selected reaction monitoring , ammonium acetate , extraction (chemistry) , acetonitrile , pharmacokinetics , mass spectrometry , analyte , high performance liquid chromatography , tandem mass spectrometry , analytical chemistry (journal) , medicine
A simple and sensitive method based on ultra‐high‐performance liquid chromatography–tandem mass spectrometry (UPLC‐MS/MS) has been developed for the determination of TM‐2, which was a novel semi‐synthetic taxane derivative in beagle dog plasma. Cabazitaxel was chosen as internal standard. Following extraction by methyl tert ‐butyl ether, the chromatographic separation was achieved on a Thermo Syncronis C 18 column (50 × 2.1 mm, 1.7 µm) by gradient elution within a runtime of 3.5 min. The mobile phase consisted of (A) acetonitrile and (B) 2 mmol/L ammonium acetate in water. The detection was accomplished using positive ion electrospray ionization in multiple reaction monitoring mode. The MS/MS ion transitions were monitored at m / z 812.39 → 551.35 for TM‐2 and 836.36 → 555.26 for IS, respectively. The method was linear for TM‐2 ( r = 0.9924) ranging from 2.5 to 1000 ng/mL. The intra‐day and inter‐day precisions (relative standard deviation) were within 8.0 and 17.6%, respectively, and the accuracy (relative error) was less than 2.3%. The extraction recovery ranged from 83.1 to 97.1%. The reliable method was successfully applied to a pharmacokinetic study of TM‐2 in beagle dogs after intravenous drip with different doses of 0.6, 1.2, and 2.4 mg/kg, respectively. Copyright © 2014 John Wiley & Sons, Ltd.