Application of a UPLC-MS/MS method to the protein binding study of TM-2 in rat, human and beagle dog plasma

作者：Liu, Hui; Wu, Pan-Pan; Yang, Ming-Jing; Men, Lei; Lin, Hong-Li; Zhao, Yun-Li; Tang, Xing; Yu, Zhi-Guo^*

来源：Journal of Pharmaceutical Analysis, 2016, 6(1): 32-38.

DOI：10.1016/j.jpha.2015.08.001

TM-2 known as a potential antitumor drug is a novel semi-synthetic taxane derivative. As drugprotein interactions contribute to insights into pharmacokinetic and pharmacodynamic properties, we elucidated the binding of TM-2 to plasma protein. In this study, a simple, rapid and reliable method was developed and validated employing equilibrium dialysis for the separation of bound and unbound drugs and ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) for the quantitation. Protein binding reached equilibrium within 24 h of incubation at 37 degrees C. After liquid-liquid extraction with methyl tert-butyl ether, the samples were separated on Thermo Syncronis UPLC (R) C-18 (2.1 mmx50 mm, 1.7 mu m), and acquisition of mass spectrometric data was performed in multiple reaction monitoring (MRM) mode via positive electrospray ionization. The assay was linear over the concentration rang of 52000 ng/mL. The intra- and inter-day precisions were 0.1%-14.8%, and the accuracy was from -6.4% to 7.0%. This assay has been successfully applied to a protein binding study of TM-2 in rat, human and beagle dog plasma. TM-2 showed high protein binding of 81.4%+/- 6.5% (rat), 87.9%+/- 3.6% (human) and 79.4%+/- 4.0% (beagle dog). The results revealed that there was an insignificant difference among the three species.

• 出版日期2016-2
• 单位沈阳药科大学