DETERMINATION OF DEXTROMETHORPHAN AND DEXTRORPHAN IN HUMAN PLASMA BY LIQUID-CHROMATOGRAPHY TANDEM MASS-SPECTROMETRY

Rapid, sensitive and selective methods were developed for the determin ation of dextromethorphan and its major metabolite, dextrorphan, in hu man plasma using liquid chromatography/tandem mass spectrometry (LC/MS /MS). Plasma samples spiked with stable-isotope internal standards wer e prepared for analysis by a liquid-liquid back-extraction procedure. Dextromethorphan and dextrorphan were chromatographed on a short rever sed-phase column, using separate isocratic mobile phase conditions opt imized to elute each compound in similar to 1.1 min. For both analytes , calibration curves were obtained over four orders of magnitude and t he limit of quantitation was 5 pg ml(-1) using a 1 mi plasma sample vo lume. The accuracy across the entire range of spiked DEX and DOR conce ntrations was, in general, within 10% of the spiked value. The precisi on was generally better than 6% for replicate sample preparations at l evels of 50 pg ml(-1) or higher and typically better than 12% at level s below 50 pg ml(-1). The method was applied for the evaluation of the pharmacokinetic profiles of dextromethorphan and dextrorphan in a hum an volunteer following peroral administration of a commercially availa ble cough formulation. (C) 1997 John Wiley & Sons, Ltd.