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 mo fetil and its active metabolite mycophenolic acid in different human skin l ayers after dermal administration is presented. The skin layers were separa ted after in vitro penetration experiments and a methanolic extraction was performed. positive ion electrospray HPLC-MS in selected ion monitoring mod e was used to quantify the substances after isocratic separation by a C-18 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 concentra tion of both drugs over the range of 25-1000 ng/ml (r(2)greater than or equ al to0.996) with accuracy less than or equal to9.8% and precision less than or equal to 13.2%. Total imprecision at quantification limits was 15.2% at 10 ng/ml and 16.3% at 1500 ng/ml for MMF and 15.1% at 21.0 ng/ml and 17.5% at 1300 ng/ml for MPA. This HPLC-MS method will be applicable to the profi ling of MMF amounts in skin and its conversion to MPA after application of different formulations. (C) 2001 Elsevier Science B.V. All rights reserved.