Determination of methamphetamine enantiomer ratios in urine by gas chromatography—mass spectrometry

Analysis of the enantiomers of methamphetamine and its metabolite amphetamine is an extremely important process for a number of scientific disciplines. From studies of biological activity and mechanisms through determination of precursor molecules in a criminal investigation are all served by this analytical procedure. Utilization of gas chromatography—mass spectrometry with chiral derivatizing reagents is the most common chiral procedure and produces excellent results. Of the chiral derivatizing reagents available, the most widely used is trifluoroacetyl-l-prolyl chloride (TPC). Utilization of other derivatives require either synthesis by the analyst or have not shown themselves to provide as good a separation as did the TPC reagent.

Use of chiral stationary phases yield good results but the disadvantages of temperature limits of these columns and the narrow use to which the columns can be put has limited their utilization. A significant utility of the chiral stationary phase is the ability to determine the purity of a chiral derivatizing reagent. Even if not used for routine analysis of enantiomers, utilization of this procedure can determine the purity of a reagent such as TPC and allow for accurate calculation of actual amounts of each enantiomer. This can be estimated using chiral derivatives on an achiral column, but it is limited to the extent that it is not able to differentiate enantiomeric impurity in the reagent versus the drug itself. Description of chromatographic procedures primarily focusing on gas chromatographic—mass spectrometric techniques but also including liquid chromatographic techniques along with examples of extraction and derivatization procedures is the focus of this review.