ASSAY OF THE ENANTIOMERS OF 1,2-PROPANEDIOL, 1,3-BUTANEDIOL, 1,3-PENTANEDIOL, AND THE CORRESPONDING HYDROXYACIDS BY GAS-CHROMATOGRAPHY MASS-SPECTROMETRY

We developed gas chromatographic-mass spectrometric assays for the ena ntiomers of 1,2-propanediol, 1,3-butanediol, 1,3-pentanediol, and thei r corresponding hydroxyacids, lactate, beta-hydroxybutyrate, and beta- hydroxypentanoate (3-hydroxyvalerate) in biological fluids. The corres ponding ketoacids, acetoacetate and beta-ketopentanoate, can be assaye d simultaneously by pretreating the samples with (NaBH4)-H-2. The assa ys involve spiking the samples with deuterated internal standards, dep roteinization, ether extraction, and derivatization of the carboxyl gr oups with (R,S)-2-butanol/HCl and of the hydroxyl groups with chiral ( S)-(+)-2-phenylbutyryl chloride. Mass spectrometric analysis is conduc ted under ammonia positive chemical ionization. We used these assays t o follow the metabolism of diol enantiomers in dogs. For (R,S)-1,3-but anediol and (R,S)-1,3-pentanediol, the uptakes from dog plasma of the R and S enantiomer of each diol were identical. In contrast, the metab olism of (S)-1,2-propanediol was faster than that of (R)-1,2-propanedi ol. (R)-1,2-Propanediol is formed during acetone metabolism, while (R, S)-1,3-butanediol and (R,S)-1,3-pentanediol are potential nutrients. T he assays developed will allow further investigations of the metabolis m of acetone, (R)-lactate, and artificial nutrients derived from the 1 ,3-butanediol and 1,3-pentanediol enantiomers. (C) 1994 Academic Press , Inc.