Negative ion chemical ionization for the determination of methylphenidate in human plasma by stable isotope dilution gas chromatography/mass spectrometry

A sensitive and specific method for the determination of methylphenidate in human plasma is presented. Methylphenidate was extracted from plasma by so lvent extraction with hexane at pH 9.3 and derivatized to its heptafluorobu tyrate derivative. The derivative was measured by gas chromatography/negati ve ion chemical ionization mass spectrometry without any further purificati on. Using this detection mode, a diagnostically useful fragment ion at m/z 369 was obtained at high relative abundance, O-18(2)-labelled methylphenida te was used as an internal standard and its rapid and facile preparation fr om the unlabeled compound is described. Calibration graphs were Linear with in the range 0.14-18.25 ng ml(-1). The inter-assay precision nas 8.7% (0.14 ng ml(-1)) and 3.1% (4.56 ng ml(-1)) and the intra-assay variability was 1 .3% (0.14 ng ml(-1)) and 0.4% (4.56 ng ml(-1)). Accuracy determinations sho wed deviations of +0.7% (0.14 ng ml(-1)) and -2.5% (4.56 ng ml(-1)). The me thod is rugged, rapid and robust and has been applied to the batch analysis of methylphenidate during pharmacokinetic profiling of the drug. Copyright (C) 2000 John Wiley & Sons, Ltd.