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

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 (50x2.1 mm, 1.7 mu m) 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 812.39551.35 for TM-2 and 836.36555.26 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 (c) 2014 John Wiley & Sons, Ltd.