Determination of norelgestromin in rabbit plasma by LC-MS/MS and its application to the pharmacokinetic study of ORTHO EVRA.
A simple, sensitive and rapid method is presented for the determination of norelgestromin using LC-MS/MS, interfaced via an electrospray ionization (ESI) probe, operating in the positive ion mode with multiple reaction monitoring (MRM). The method was developed and validated over the concentration range of 0.05-20 ng/ml, and showed excellent linearity. The intra- and inter-assay accuracy error and precision were ranging from -2.3% to 6.0% of nominal values and 2.2% to 7.8% over the three concentration levels evaluated. The concentration of formic acid in mobile phase was optimized to achieve satisfactory injection reproducibility and sensitivity, and sample preparation was optimized, with only 1.6 ml organic solvents used in performing the liquid-liquid extraction. The method has been successfully applied to a pharmacokinetic study of the ORTHO EVRA patch in rabbits.
Liu
Xiaofen
X
Shanghai Institute of Pharmaceutical Industry, National Pharmaceutical Engineering and Research Center, Shanghai 201203, PR China.
Ding
Cungang
C
Ge
Qinghua
Q
Zhi
Xiaojin
X
Zhou
Zhen
Z
D000818:Animals; D002853:Chromatography, Liquid; D003277:Contraceptives, Oral, Combined / Q000097:blood* / Q000493:pharmacokinetics; D004338:Drug Combinations; D004355:Drug Stability; D004997:Ethinyl Estradiol / Q000493:pharmacokinetics*; D005260:Female; D016014:Linear Models; D009644:Norgestrel / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics; D010091:Oximes / Q000097:blood / Q000493:pharmacokinetics; D011817:Rabbits; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D053719:Tandem Mass Spectrometry / Q000379:methods*
D003277:Contraceptives, Oral, Combined; D004338:Drug Combinations; C511292:Ortho Evra; D010091:Oximes; D009644:Norgestrel; D004997:Ethinyl Estradiol; C449219:norelgestromin