Simultaneous Chiral Analysis of Methamphetamine and its Metabolites by Capillary Electrophoresis/Mass Spectrometry with Direct Injection of Urine

Abstract

We describe a rapid and simple method for the analysis of the d- and l-isomers of seven methamphetamine-related compounds and the d-isomer of pseudoephedrine (pseudoEP) by capillary electrophoresis/mass spectrometry (CE/MS) with direct injection of urine. The compounds were methamphetamine (MA), amphetamine (AP), dimethylamphetamine, ephedrine, norephedrine, methylephedrine, p-hydroxymethamphetamine (pOHMA). The electrolyte was 1 M formic acid/1 M ammonium formate (10/0.2, v/v) (pH 2.0) containing 1.5 mM heptakis-(2,6-diacetyl-6-sulfato)-β-cyclodextrin. The 14 enantiomers and d-pseudoEP were completely separated within 30 min. A urine sample was mixed with an equal volume of internal standard solution, filtered with a 0.45 μm filter and then injected into the CE/MS system. In an analysis of urine sample from a healthy person spiked with racemic MA and AP, the reproducibilities (n = 6) of the migration times and peak areas after correction by an internal standard were under 0.08% and under 3.6%, respectively. The detection limits using selected ion monitoring were 0.01 μg/ml (which corresponds to 0.02 μg/ml urine) for the enantiomers of MA, AP and pOHMA. The detection yields of the enantiomers of MA, AP and pOHMA from urine were in the range of 97.7-108.8%. The proposed method was successfully used for the chiral analysis of urine samples from MA and dimethylamphetamine (DMA) addicts and patients under selegiline pharmacotherapy.