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 enantiomers of 1,2-propanediol, 1,3-butanediol, 1,3-pentanediol, and their corresponding hydroxyacids, lactate, β-hydroxybutyrate, and β-hydroxypentanoate (3-hydroxyvalerate) in biological fluids. The corresponding ketoacids, acetoacetate and β-ketopentanoate, can be assayed simultaneously by pretreating the samples with (NaB 2H 4). The assays involve spiking the samples with deuterated internal standards, deproteinization, ether extraction, and derivatization of the carboxyl groups with ( R, S)-2-butanol/HCl and of the hydroxyl groups with chiral ( S)-(+)-2-phenylbutyryl chloride. Mass spectrometric analysis is conducted under ammonia positive chemical ionization. We used these assays to follow the metabolism of diol enantiomers in dogs. For ( R, S)-1,3-butanediol 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 metabolism of ( S)-1,2-propanediol was faster than that of ( R)-1,2-propanediol. ( R)-1,2-Propanediol is formed during acetone metabolism, while ( R, S)-1,3-butanediol and ( R, S)-1,3-pentanediol are potential nutrients. The assays developed will allow further investigations of the metabolism of acetone, ( R)-lactate, and artificial nutrients derived from the 1,3-butanediol and 1,3-pentanediol enantiomers.