title: A novel UPLC/MS/MS method for rapid determination of metapristone in rat plasma, a new cancer metastasis chemopreventive agent derived from mifepristone (RU486).
abstract: Mifepristone (RU486) is a chemical abortifacient used by hundreds of millions of women world-wide. It has recently been used in clinical trials for psychotic depression and cancer chemotherapy. Metapristone is the most predominant biological active metabolite of mifepristone, and being developed as a novel cancer metastasis chemopreventive agent based on its unique pharmacological properties. In this study, a novel rapid and sensitive method using UPLC/MS/MS was developed and validated for quantitative analysis of metapristone in plasma, which used less plasma volume and was demonstrated to be more simple and low-cost than the published methods. Metapristone in plasma was recovered by liquid-liquid extraction using 1 mL of ethyl acetate and chromatographic separation was carried on a C₁₈ column at 35 °C, with a gradient mobile phase consisting of methanol and water containing 0.1% (v/v) formic acid at a flow rate of 0.3 mL/min. The mass spectrometric detection was carried out using a triple-quadrupole system via positive electrospray ionization. Multiple reaction monitoring was used for quantitation of m/z transitions from 416.3 to 119.9 for metapristone and from 313.1 to 109 for levonorgestrel (internal standard). Good linearity (r²> 0.9926) was achieved over a concentration range from 7.1 to 2840 ng/mL with a lower limit of quantification of 7.1 ng/mL for metapristone. The intra- and inter-day variations of the assay were 2.4-10.0% relative standard deviation with an accuracy of -5.6 to 8.6% relative error. This newly developed method was successfully applied to a pharmacokinetic study that revealed, for the first time, that there was a significant difference in pharmacokinetic profile between genders.
authors.affiliation: Cancer Metastasis Alert and Prevention Center, College of Chemistry and Chemical Engineering, Fuzhou University, Fuzhou 350002, China; School of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou 350108, China.
authors.forename: Jian-Zhong
authors.initials: JZ
authors.lastname: Chen
authors.affiliation: Cancer Metastasis Alert and Prevention Center, College of Chemistry and Chemical Engineering, Fuzhou University, Fuzhou 350002, China.
authors.forename: Ji-Chuang
authors.initials: JC
authors.lastname: Wang
authors.affiliation: Cancer Metastasis Alert and Prevention Center, College of Chemistry and Chemical Engineering, Fuzhou University, Fuzhou 350002, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Gao
authors.affiliation: School of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou 350108, China.
authors.forename: Rong-Jie
authors.initials: RJ
authors.lastname: Zeng
authors.affiliation: Cancer Metastasis Alert and Prevention Center, College of Chemistry and Chemical Engineering, Fuzhou University, Fuzhou 350002, China.
authors.forename: Zhou
authors.initials: Z
authors.lastname: Jiang
authors.affiliation: Cancer Metastasis Alert and Prevention Center, College of Chemistry and Chemical Engineering, Fuzhou University, Fuzhou 350002, China.
authors.forename: Ye-Wei
authors.initials: YW
authors.lastname: Zhu
authors.affiliation: Cancer Metastasis Alert and Prevention Center, College of Chemistry and Chemical Engineering, Fuzhou University, Fuzhou 350002, China.
authors.forename: Jing-Wei
authors.initials: JW
authors.lastname: Shao
authors.affiliation: Cancer Metastasis Alert and Prevention Center, College of Chemistry and Chemical Engineering, Fuzhou University, Fuzhou 350002, China. Electronic address: pharmlink@gmail.com.
authors.forename: Lee
authors.initials: L
authors.lastname: Jia
mesh_terms: D000818:Animals; D016588:Anticarcinogenic Agents / Q000097:blood*; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D005260:Female; D057230:Limit of Detection; D008297:Male; D015735:Mifepristone / Q000031:analogs & derivatives* / Q000097:blood; D051381:Rats; D017207:Rats, Sprague-Dawley; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D016588:Anticarcinogenic Agents; D015735:Mifepristone; C000592521:metapristone
keywords: Cancer metastasis chemopreventive agent; Metapristone; Mifepristone; Pharmacokinetics; UPLC/MS/MS