Quantification of mycophenolate mofetil in human skin extracts using high-performance liquid chromatography-electrospray mass spectrometry.
A sensitive and selective method for the quantification of mycophenolate mofetil and its active metabolite mycophenolic acid in different human skin layers after dermal administration is presented. The skin layers were separated after in vitro penetration experiments and a methanolic extraction was performed. Positive ion electrospray HPLC-MS in selected ion monitoring mode was used to quantify the substances after isocratic separation by a C18 analytical column. The minimum detectable concentrations were 850 pg/ml for MMF and 1 ng/ml for MPA. The peak areas depended linearly on the concentration of both drugs over the range of 25-1,000 ng/ml (r2 > or = 0.996) with accuracy < or =9.8% and precision < or = 13.2%. Total imprecision at quantification limits was 15.2% at 10 ng/ml and 16.3% at 1,500 ng/ml for MMF and 15.1% at 21.0 ng/ml and 17.5% at 1,300 ng/ml for MPA. This HPLC-MS method will be applicable to the profiling of MMF amounts in skin and its conversion to MPA after application of different formulations.
Plätzer
M
M
Martin-Luther-University, Department of Pharmacy, Institute of Pharmaceutics and Biopharmaceutics, Halle Saale, Germany.
Jahn
K
K
Wohlrab
J
J
Neubert
R H
RH
D002851:Chromatography, High Pressure Liquid / Q000379:methods; D006801:Humans; D007166:Immunosuppressive Agents / Q000032:analysis*; D013058:Mass Spectrometry; D009173:Mycophenolic Acid / Q000031:analogs & derivatives / Q000032:analysis*; D011355:Prodrugs / Q000032:analysis*; D012867:Skin / Q000737:chemistry*
D007166:Immunosuppressive Agents; D011355:Prodrugs; D009173:Mycophenolic Acid