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.
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 51.58-20,630 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.
Research Center for Clinical Pharmacy, State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, First Affiliated Hospital, Zhejiang University, Hangzhou, 310003, China.
Huili
H
Zhou
Research Center for Clinical Pharmacy, State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, First Affiliated Hospital, Zhejiang University, Hangzhou, 310003, China.
Yunliang
Y
Zheng
Guangdong Zonk Drug R&D Limited, Guangdong, Guangzhou, 510730, China.
Yanan
Y
Liu
Research Center for Clinical Pharmacy, State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, First Affiliated Hospital, Zhejiang University, Hangzhou, 310003, China.
Xingjiang
X
Hu
Research Center for Clinical Pharmacy, State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, First Affiliated Hospital, Zhejiang University, Hangzhou, 310003, China.
Guolan
G
Wu
Research Center for Clinical Pharmacy, State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, First Affiliated Hospital, Zhejiang University, Hangzhou, 310003, China.
Jianzhong
J
Shentu
D000818:Animals; D000970:Antineoplastic Agents / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics; D002853:Chromatography, Liquid / Q000379:methods*; D003374:Coumarins / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics; D016014:Linear Models; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D021241:Spectrometry, Mass, Electrospray Ionization; D053719:Tandem Mass Spectrometry / Q000379:methods*
D000970:Antineoplastic Agents; D003374:Coumarins
LC-MS/MS; copen; pharmacokinetics; preclinical