Autor: |
Hui Liu, Pan-Pan Wu, Ming-Jing Yang, Lei Men, Hong-Li Lin, Yun-Li Zhao, Xing Tang, Zhi-Guo Yu |
Jazyk: |
angličtina |
Rok vydání: |
2016 |
Předmět: |
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Zdroj: |
Journal of Pharmaceutical Analysis, Vol 6, Iss 1, Pp 32-38 (2016) |
Druh dokumentu: |
article |
ISSN: |
2095-1779 |
DOI: |
10.1016/j.jpha.2015.08.001 |
Popis: |
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. |
Databáze: |
Directory of Open Access Journals |
Externí odkaz: |
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