Application of a UPLC–MS/MS method to the protein binding study of TM-2 in rat, human and beagle dog plasma
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 d...
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doaj-caf80a262fee494a860bbd937fb035b02021-04-02T08:12:10ZengElsevierJournal of Pharmaceutical Analysis2095-17792016-02-0161323810.1016/j.jpha.2015.08.001Application of a UPLC–MS/MS method to the protein binding study of TM-2 in rat, human and beagle dog plasmaHui Liu0Pan-Pan Wu1Ming-Jing Yang2Lei Men3Hong-Li Lin4Yun-Li Zhao5Xing Tang6Zhi-Guo Yu7School of Pharmacy, Shenyang Pharmaceutical University, Wenhua Road 103, Shenhe District, Shenyang 110016, ChinaSchool of Pharmacy, Shenyang Pharmaceutical University, Wenhua Road 103, Shenhe District, Shenyang 110016, ChinaSchool of Pharmacy, Shenyang Pharmaceutical University, Wenhua Road 103, Shenhe District, Shenyang 110016, ChinaSchool of Pharmacy, Shenyang Pharmaceutical University, Wenhua Road 103, Shenhe District, Shenyang 110016, ChinaSchool of Pharmacy, Shenyang Pharmaceutical University, Wenhua Road 103, Shenhe District, Shenyang 110016, ChinaSchool of Pharmacy, Shenyang Pharmaceutical University, Wenhua Road 103, Shenhe District, Shenyang 110016, ChinaSchool of Pharmacy, Shenyang Pharmaceutical University, Wenhua Road 103, Shenhe District, Shenyang 110016, ChinaSchool of Pharmacy, Shenyang Pharmaceutical University, Wenhua Road 103, Shenhe District, Shenyang 110016, ChinaTM-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.http://www.sciencedirect.com/science/article/pii/S2095177915300058TM-2Plasma protein bindingUPLC–MS/MS |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Hui Liu Pan-Pan Wu Ming-Jing Yang Lei Men Hong-Li Lin Yun-Li Zhao Xing Tang Zhi-Guo Yu |
spellingShingle |
Hui Liu Pan-Pan Wu Ming-Jing Yang Lei Men Hong-Li Lin Yun-Li Zhao Xing Tang Zhi-Guo Yu Application of a UPLC–MS/MS method to the protein binding study of TM-2 in rat, human and beagle dog plasma Journal of Pharmaceutical Analysis TM-2 Plasma protein binding UPLC–MS/MS |
author_facet |
Hui Liu Pan-Pan Wu Ming-Jing Yang Lei Men Hong-Li Lin Yun-Li Zhao Xing Tang Zhi-Guo Yu |
author_sort |
Hui Liu |
title |
Application of a UPLC–MS/MS method to the protein binding study of TM-2 in rat, human and beagle dog plasma |
title_short |
Application of a UPLC–MS/MS method to the protein binding study of TM-2 in rat, human and beagle dog plasma |
title_full |
Application of a UPLC–MS/MS method to the protein binding study of TM-2 in rat, human and beagle dog plasma |
title_fullStr |
Application of a UPLC–MS/MS method to the protein binding study of TM-2 in rat, human and beagle dog plasma |
title_full_unstemmed |
Application of a UPLC–MS/MS method to the protein binding study of TM-2 in rat, human and beagle dog plasma |
title_sort |
application of a uplc–ms/ms method to the protein binding study of tm-2 in rat, human and beagle dog plasma |
publisher |
Elsevier |
series |
Journal of Pharmaceutical Analysis |
issn |
2095-1779 |
publishDate |
2016-02-01 |
description |
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. |
topic |
TM-2 Plasma protein binding UPLC–MS/MS |
url |
http://www.sciencedirect.com/science/article/pii/S2095177915300058 |
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