Chemometrics-assisted chromatographic fingerprinting: An illicit methamphetamine case study

Abstract

The volatile chemical constituents in complex mixtures can be analyzed using gas chromatography with mass spectrometry. This analysis allows the tentative identification of diverse impurities of an illicit methamphetamine sample. The acquired two-dimensional data of liquid-liquid extraction was resolved by multivariate curve resolution alternating curve resolution to elucidate the embedded peaks effectively. This is the first report on the application of a curve resolution approach for chromatogram fingerprinting to identify particularly the embedded impurities of a drug of abuse. Indeed, the strong and broad peak of methamphetamine makes identifying the underlying peaks problematic and even impossible. Mathematical separation instead of conventional chromatographic approaches was performed in a way that trace components embedded in methamphetamine peak were successfully resolved. Comprehensive analysis of the chromatogram, using multivariate curve resolution, resulted in elution profiles and mass spectra for each pure compound. Impurities such as benzaldehyde, benzyl alcohol, benzene, propenyl methyl ketone, benzyl methyl ketone, amphetamine, N-benzyl-2-methylaziridine, phenethylamine, N,N,α-trimethylamine, phenethylamine, N,α,α-trimethylmethamphetamine, N-acetylmethamphetamine, N-formylmethamphetamine, and other chemicals were identified. A route-specific impurity, N-benzyl-2-methylaziridine, indicating a synthesis route based on ephedrine/pseudoephedrine was identified. Moreover, this is the first report on the detection of impurities such as phenethylamine, N,α,α-trimethylamine (a structurally related impurity), and clonitazene (as an adulterant) in an illicit methamphetamine sample.

Methamphetamine (N-methylamphetamine)-induced renal disease: underevaluated cause of end-stage renal disease (ESRD)

“…Some of the impurities reported in the literature include N -isopropyl benzylamine, cocaine, phenethylamine and acetic acid 20 21…”

DARK Classics in Chemical Neuroscience: Etonitazene and Related Benzimidazoles

“…Curiously, two publications have claimed the identification by GC–MS of clonitazene as an environmental contaminant: in wastewater at the Rhone area near Lyon, France, and in air particulate matter under foggy weather in Wuhan, China . Clonitazene has also been reported as an impurity in an illicit methamphetamine sample …”

Interpol review of controlled substances 2016–2019

“…Methamphetamine: 2016 fluorescent film for detecting n-methamphetamine in vapor with a detection limit of 5.5 ppb [ 239 ], analysis of impurities in methamphetamine using a liquid-liquid extraction (LLE) method and analysis by GC-FID [ 240 ]; electrochemiluminescence for the direct detection of methylamphetamine and other amphetamine type stimulants in street samples and biological matrices without the need for pretreatment or extraction [ 241 ]; capillary microextraction for sampling of methamphetamine vapor at clandestine laboratories [ 242 ]; method to estimate the consumption and prevalence of methamphetamine based on wastewater analysis [ 243 ]; impurity characterization of seized methamphetamine crystals by GC-MS [ 244 ]; visual detection of methamphetamine and MDMA in the low micromolar range using gold nanoparticles as a colorimetric probe [ 245 ]; optimization of an electrochemical method to detect methamphetamine [ 246 ]; estimation of the synthetic routes of seized methamphetamines using GC-MS and multivariate analysis [ 247 ]; G-quadruplex-hemin DNAzyme molecular beacon probe for the detection of methamphetamine [ 248 ]; improved chiral separation of Methamphetamine enantiomers Using CSP-LC-MS/MS [ 249 ]; 2017 benchtop NMR for the analysis of samples from suspected clandestine laboratories [ 250 ]; impurity profiling of methamphetamine synthesized from clandestine methylamine [ 251 ]; remediating interior building surfaces contaminated by methamphetamine [ 252 ]; mobile application with evidence-based information on crystal methamphetamine [ 253 ]; airborne methamphetamine sampling using capillary microextraction [ 254 ]; chiral supercritical fluid chromatography method for differentiation of methamphetamine enantiomers in forensic samples [ 255 ]; mathematical separation instead of conventional chromatographic approaches to resolve trace impurities embedded in the methamphetamine peak [ 256 ]; isolation and characterization of trans-N-methyl-4-methyl-5-phenyl-4-penten-2-amine hydrochloride, trace processing impurity found in some methamphetamine samples [ 257 ]; fluorescence and chemiluminescence procedures for methamphetamine determination [ 258 ]; 2018 developed a simple and effective physical characteristic profiling method for Methamphetamine tablets with capital letter WY logos, which realized the discrimination between linked and unlinked tablet seizures from 2011 to 2015 in China, indicating the existence of a huge clandestine factory incessantly manufacturing methamphetamine tablets [ 259 ]; a dilute-and-shoot UHPLC-MS/MS method for the simultaneous identification and quantitation of 23 organic manufacturing impurities in illicit methamphetamine [ 260 ]; a complete synthesis of methamphetamine and analysis of the final product by both GC-MS and ESI-MS to identify impurities […”