Simultaneous determination of mifepristone and monodemethyl-mifepristone in human plasma by liquid chromatography-tandem mass spectrometry method using levonorgestrel as an internal standard: application to a pharmacokinetic study.
A rapid and sensitive liquid chromatography/tandem mass spectrometry (LC-MS/MS) method was developed and validated to simultaneously determine mifepristone and monodemethyl-mifepristone in human plasma using levonorgestrel as the internal standard (IS). After solid-phase extraction of the plasma samples, mifepristone, monodemethyl-mifepristone and the IS were subjected to LC-MS/MS analysis using electro-spray ionization (ESI) in the multiple reaction monitoring (MRM) mode. Chromatographic separation was performed on an XTERRA MS C(18) column (150 x 2.1 mm i.d., 5 microm). The method had a chromatographic run time of 4.5 min and linear calibration curves over the concentration ranges of 5-2000 ng/mL for mifepristone and monodemethyl-mifepristone. The recoveries of the method were found to be 94.5-103.7% for mifepristone and 70.7-77.3% for monodemethyl-mifepristone. The method had a lower limit of quantification (LLOQ) of 5.0 ng/mL and a lower limit of detection (LOD) of 1.0 ng/mL for both mifepristone and monodemethyl-mifepristone. The intra- and inter-batch precision was less than 15% for all quality control samples at concentrations of 10, 100 and 1000 ng/mL. These results indicate that the method was efficient with a short run time (4.5 min) and acceptable accuracy, precision and sensitivity. The validated LC-MS/MS method was successfully used in a pharmacokinetic study in healthy female volunteers after oral administration of 25 mg mifepristone tablet.
Tang
Cheng
C
Institute of Clinical Pharmacology, School of Pharmaceutical Sciences, Sun Yat-sen University, 74 Zhongshan Road II, Guangzhou 510080, People's Republic of China.
Bi
Hui-Chang
HC
Zhong
Guo-Ping
GP
Chen
Xiao
X
Huang
Zhi-Ying
ZY
Huang
Min
M
D002853:Chromatography, Liquid / Q000379:methods*; D006801:Humans; D016912:Levonorgestrel / Q000032:analysis* / Q000592:standards; D015735:Mifepristone / Q000031:analogs & derivatives / Q000097:blood*; D012015:Reference Standards; D015203:Reproducibility of Results; D053719:Tandem Mass Spectrometry / Q000379:methods*
D015735:Mifepristone; D016912:Levonorgestrel