Quantification of an antitumor agent (copen) in rat plasma by liquid chromatography–electrospray ionization tandem mass spectrometry and its application in a preclinical pharmacokinetic study |
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| Authors: | Huili Zhou Yunliang Zheng Yanan Liu Xingjiang Hu Guolan Wu Jianzhong Shentu |
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| Affiliation: | 1. Research Center for Clinical Pharmacy, State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, First Affiliated Hospital, Zhejiang University, Hangzhou, China;2. Guangdong Zonk Drug R&D Limited, Guangdong, Guangzhou, China |
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| Abstract: | Copen is a derivative obtained from the structural modification of osthole, which inhibits tumoral proliferation in many tumor cell lines. A rapid and sensitive liquid chromatography–tandem mass spectrometry (LC‐MS/MS) method was established for the quantification of copen in rat plasma. After a simple sample preparation procedure by one‐step protein precipitation with methanol, copen and bicalutamide (internal standard, IS) were chromatographed on a Zorbax SB‐C18 (4.6×100 mm, 1.8 µm) column with a mobile phase consisting of methanol–5 mm ammonium formate water with 0.1% formic acid (80:20, v/v). MS detection was performed on a triple quadrupole tandem mass spectrometer in the multiple reaction monitoring mode with a positive eletrospray ionization source. The assay was validated in the concentration range of 51.58–20630 ng/mL, with a limit of quantitation (LOQ) of 51.58 ng/mL. The intra‐ and inter‐day precisions (relative standard deviation) were ≤3.21 and ≤11.3%, respectively, with accuracy (%) in the range of 94.66–102.1%. The method was fully validated in a study of the pharmacokinetics of copen (25 mg/kg) after intragastric administration in rats. Copyright © 2014 John Wiley & Sons, Ltd. |
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| Keywords: | copen LC‐MS/MS pharmacokinetics preclinical |
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