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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
Author(s) -
Zhou Huili,
Zheng Yunliang,
Liu Yanan,
Hu Xingjiang,
Wu Guolan,
Shentu Jianzhong
Publication year - 2015
Publication title -
biomedical chromatography
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.4
H-Index - 65
eISSN - 1099-0801
pISSN - 0269-3879
DOI - 10.1002/bmc.3375
Subject(s) - chemistry , chromatography , ammonium formate , protein precipitation , formic acid , electrospray ionization , selected reaction monitoring , mass spectrometry , tandem mass spectrometry , detection limit , liquid chromatography–mass spectrometry , pharmacokinetics , medicine
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‐C 18 (4.6×100 mm, 1.8 µm) column with a mobile phase consisting of methanol–5 m m 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.