S. Zaugg et W. Thormann, Chiral capillary electrophoresis of the methaqualone rotamers: Indication of a stereoselective metabolism, J MICROCOL, 13(3), 2001, pp. 96-101
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.