QUANTIFICATION OF S-CARBOXYMETHYL-(R)-CYSTEINE IN HUMAN PLASMA BY HIGH-PERFORMANCE ION-EXCHANGE LIQUID-CHROMATOGRAPHY ATMOSPHERIC-PRESSURE IONIZATION MASS-SPECTROMETRY

The determination of S-carboxynnethyl-(R)-cysteine (SCMC) in human pla sma during extended bioequivalence studies demands a rapid, accurate a nd selective assay technique. A liquid chromatographic/mass spectromet ric method was developed which involves rough protein precipitation fo llowed by high-performance liquid chromatographic separation with an i on-exchange column and atmospheric pressure ionization (API) mass spec trometric detection, with the instrument operating with electrospray i onization (ESI) and in the selected-ion monitoring mode. The drug and the internal standard S-[(R)-1-carboxyethyl]-(R)-cysteine (SCEC) are d etected by focusing the first quadrupole of the triple stage system on MH+ ions, thus permitting elimination of endogenous interfering subst ances and allowing a detection limit of 0.05 mu g ml(-1). The chromato graphic run time is 16 min and the method has sufficient sensitivity, precision, accuracy and selectivity for routine analyses of clinical p lasma samples containing SCMC at concentrations in the range 0.2-20 mu g ml(-1). In summary, this LC/MS-based assay of SCMC demonstrates adv antages of easy sample preparation, low limit of quantification (200 n g per ml of human plasma) without any derivatization step, high specif icity and rapid sample analysis with an overall throughput of more tha n 60 analyses per day. (C) 1997 by John Wiley & Sons, Ltd.