Chiral capillary electrophoresis of the methaqualone rotamers: Indication of a stereoselective metabolism

Methaqualone (MQ, 2-methyl-3-o-tolylquinazolin-4(3H)-one) is a hypnotic and anticonvulsive drug in which the rotation about the nitrogen-to-aryl bond between the planar 2-methyl-quinazolin-4(3H)-one structure and the o-tolyl moiety is sterically hindered. MQ is thus a chiral substance whose enantiom ers are shown to be separable by acidic chiral capillary electrophoresis (C E) in presence of (2-hydroxypropyl)-beta -cyclodextrin (OHP-beta -CD). Usin g a pH 2.5 phosphate buffer containing 8 mM OHP-beta -CD, chiral discrimina tion is possible up to an intracapillary temperature of at least 70 degrees C. For a given capillary length, optimized separation is attained at the lo west running temperature. CE is demonstrated to be a simple and an attracti ve approach for analysis of MQ enantiomers in alkaline extracts of urines t hat were collected after single-dose administration of a tablet containing 250 mg MQ. Electropherograms obtained with urines collected at different ti me intervals after drug intake reveal that the size ratio of the two peaks allocated to MQ is changing with time, thus indicating the existence of a s tereoselective metabolism of that drug. For unambiguous elucidation of the stereoselectivity, however, chiral analyses of urinary MQ metabolites will have to be undertaken. (C) 2001 John Wiley & Sons, Inc.