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

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• 作者：Hui Liu^a ; ^b ; Pan-Pan Wu^a ; Ming-Jing Yang^a ; Lei Men^a ; Hong-Li Lin^a ; Yun-Li Zhao^a ; Xing Tang^a ; Zhi-Guo Yu^a ; ^{zhiguo-yu@163.com" class="auth_mail" title="E-mail the corresponding author}
• 关键词：TM-2 ; Plasma protein binding ; UPLC&ndash ; MS/MS
• 刊名：Journal of Pharmaceutical Analysis
• 出版年：2016
• 出版时间：February 2016
• 年：2016
• 卷：6
• 期：1
• 页码：32-38
• 全文大小：1156 K

文摘

TM-2 known as a potential antitumor drug is a novel semi-synthetic taxane derivative. As drug–protein 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 °C. After liquid–liquid extraction with methyl tert-butyl ether, the samples were separated on Thermo Syncronis UPLC^® C₁₈ (2.1 mm×50 mm, 1.7 µm), 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 5–2000 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.