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

•Thirty organic impurities in MA samples were detected by the DART-HRMS to infer the synthetic route.•The PLS-DA model was established from known MA samples and was used to infer the synthetic pathway of unknown MA samples.•The synthetic pathway of actual MA was determined to provide information for the detection of samples. 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.