Estimation of synthetic route of methamphetamine samples seized in China by direct analysis in real time with high-resolution mass spectrometry and chemometric analysis of organic impurities

Abstract

A direct analysis in real time combined with high-resolution mass spectrometry (DART-HRMS) method was established to quickly detect organic impurities in methamphetamine (MA) samples. A partial least-squares discriminant analysis (PLS-DA) model was established by using MA samples with known synthetic pathways, and the synthetic pathways of unknown MA were determined by the PLS-DA model. The PLS-DA model was used to analyze characteristic organic impurities, which were identified as chemical markers in different synthetic-pathway MA samples by VIP (Variable Importance for the Projection) values and p-values. Thirty organic impurities were determined by DART-HRMS. Among these compounds, 7 organic impurities had a VIP value greater than 1, which indicated specificity for the grouping, including amphetamine, 1-phenylpropan-2-one oxime, N-formylamphetamine, ephedrine/pseudoephedrine, bibenzyl, α-methyldiphenethylamine and 1,3-diphenylacetone, while 5 organic impurities played a important role in classifying three groups. Amphetamine and 1-phenylpropan-2-one oxime played an important role in the R group, which represented MA samples using 1-phenyl-2-propanone as a starting material in the reductive amination reaction. Bibenzyl was important in the N group, in which MA samples were produced by ephedrine or pseudoephedrine and the iodine /phosphorus (I/P) (Nagai, Moscow, or Hypo) method. Ephedrine/pseudoephedrine and α–methyldiphenethylamine were important in the E group, in which samples were produced by ephedrine or pseudoephedrine and the catalytic hydrogenation method. The established PLS-DA model was also used to analyse MA samples of unknown synthetic routes. This established method is simple and fast and can achieve high-throughput analysis of samples to save time and analyse more samples. The analysis results provide effective information for drug law enforcement agencies.