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Vol. 26 No. 2 (2014): Vol 26 Issue 2

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Application of LC-MS/MS Method for Evaluating Rosuvastatin Affinity with OATP1B1 and OATP2B1 in vitro

https://doi.org/10.14233/ajchem.2014.15376
Zhi-Yu Zhang1
1School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072, P.R. China 2State Key Laboratory of Drug Delivery Technology and Pharmacokinetics, Tianjin Institute of Pharmaceutical Research, Tianjin 300193, P.R. China *Corresponding authors: Tel/Fax: +86 22 84845242; E-mail: yixl@tjipr.com; liucx@tjipr.com
Quan-Sheng Li2
1School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072, P.R. China 2State Key Laboratory of Drug Delivery Technology and Pharmacokinetics, Tianjin Institute of Pharmaceutical Research, Tianjin 300193, P.R. China *Corresponding authors: Tel/Fax: +86 22 84845242; E-mail: yixl@tjipr.com; liucx@tjipr.com
Duan-Yun Si2
1School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072, P.R. China 2State Key Laboratory of Drug Delivery Technology and Pharmacokinetics, Tianjin Institute of Pharmaceutical Research, Tianjin 300193, P.R. China *Corresponding authors: Tel/Fax: +86 22 84845242; E-mail: yixl@tjipr.com; liucx@tjipr.com
Xiu-Lin Yi2
1School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072, P.R. China 2State Key Laboratory of Drug Delivery Technology and Pharmacokinetics, Tianjin Institute of Pharmaceutical Research, Tianjin 300193, P.R. China *Corresponding authors: Tel/Fax: +86 22 84845242; E-mail: yixl@tjipr.com; liucx@tjipr.com
Chang-Xiao Liu2
1School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072, P.R. China 2State Key Laboratory of Drug Delivery Technology and Pharmacokinetics, Tianjin Institute of Pharmaceutical Research, Tianjin 300193, P.R. China *Corresponding authors: Tel/Fax: +86 22 84845242; E-mail: yixl@tjipr.com; liucx@tjipr.com

Asian Journal of Chemistry, Vol. 26 No. 2 (2014): Vol 26 Issue 2

Abstract

Drug-drug interaction is one of the most important preclinical investigation directions. It may have serious impact on drug absorption, distribution and elimination through membrane transporters. Liquid chromatography/Tandem mass spectrometry (LC/MS/MS) could be used to investigate drug-drug interaction in vitro. A sensitive LC/MS/MS method was established for quantification of rosuvastatin in HEK293 and S2 cell lysates. Internal standard (IS) was indapamide. Detection mode was positive electrospray ionization. The lower limit of quantification (LLOQ) was 0.05 ng/mL. The affinity of rosuvastatin with organic anion-transporting polypeptides 1B1 and 2B1 (OATP1B1 and OATP2B1) was investigated through uptake experiment. All cell samples were precipitated with methanol. Analytes were separated by reversed-phase chromatography and analyzed by Tandem mass spectrometry using m/z 482.2/ 258.1 for rosuvastatin and m/z 366.1/132.1 for indapamide. Rosuvastatin uptake was saturable with Km value of 11.70 and 5.98 μM for OATP1B1 and OATP2B1. Rosuvastatin could be used as a good probe for studying membrane transporter activity and drug-drug interaction through LC/MS/MS method.

Keywords

LC/MS/MS Transporter Rosuvastatin OATP1B1 OATP2B1.
Zhang1, Z.-Y., Li2, Q.-S., Si2, D.-Y., Yi2, X.-L., & Liu2, C.-X. (2014). Application of LC-MS/MS Method for Evaluating Rosuvastatin Affinity with OATP1B1 and OATP2B1 in vitro. Asian Journal of Chemistry, 26(2), 335–341. https://doi.org/10.14233/ajchem.2014.15376
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