Simultaneous determination of myristyl nicotinate, nicotinic acid, and nicotinamide in rabbit plasma by liquid chromatography–tandem mass spectrometry using methyl ethyl ketone as a deproteinization solvent

摘要: Myristyl nicotinate (Nia-114) is an ester prodrug being developed for delivery of nicotinic acid (NIC) into the skin prevention actinic keratosis and its progression to cancer. To facilitate dermal studies Nia-114, a novel liquid chromatography-tandem mass spectrometry (LC-MS/MS) method using methyl ethyl ketone (MEK) as deproteinization solvent was validated simultaneous determination NIC, nicotinamide (NAM) in rabbit plasma. NAM principal metabolite which also expected have chemopreventive properties. The analytes were chromatographically separated Spherisorb Cyano column under isocratic conditions, detected by multiple reaction monitoring (MRM) positive-ion electrospray ionization mode with run time 9 min. utilized plasma sample volume 0.2 ml isotope-labeled D4 forms each analyte internal standards. linear over concentration range 2-1000, 8-1000, 75-1000 ng/ml, NAM, respectively. intra- inter-day assay accuracy precision within +/-15% all at low, medium, high quality control standard levels. relatively value lower limit quantitation (LLOQ) demonstrated be due level endogenous (about 350 ng/ml). Endogenous levels NIC human, dog, rat, mouse determined, mean values ranged from <2 ng/ml 38.3 233 622 mouse. Nia-114 generally unstable plasma, evidenced loss 44-50% room temperature 2 h, 64-70% upon storage -20 degrees C 1 week, whereas it stable (<7% loss) -80 month.