Simultaneous detection and quantitation of organic impurities in methamphetamine by ultra‐high‐performance liquid chromatography–tandem mass spectrometry, a complementary technique for methamphetamine profiling

Abstract

The analysis of organic impurities plays an important role in the impurity profiling of methamphetamine, which in turn provides valuable information about methamphetamine manufacturing, in particular its synthetic route, chemicals, and precursors used. Ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) is ideally suited for this purpose due to its excellent sensitivity, selectivity, and wide linear range in multiple reaction monitoring (MRM) mode. In this study, a dilute-and-shoot UHPLC-MS/MS method was developed for the simultaneous identification and quantitation of 23 organic manufacturing impurities in illicit methamphetamine. The developed method was validated in terms of stability, limit of detection (LOD), lower limit of quantification (LLOQ), accuracy, and precision. More than 100 illicitly prepared methamphetamine samples were analyzed. Due to its ability to detect ephedrine/pseudoephedrine and its high sensitivity for critical target markers (eg, chloro-pseudoephedrine, N-cyclohexylamphetamine, and compounds B and P), more impurities and precursor/pre-precursors were identified and quantified versus the current procedure by gas chromatography-mass spectrometry (GC-MS). Consequently, more samples could be classified by their synthetic routes. However, the UHPLC-MS/MS method has difficulty in detecting neutral and untargeted emerging manufacturing impurities and can therefore only serve as a complement to the current method. Despite this deficiency, the quantitative information acquired by the presented UHPLC-MS/MS methodology increased the sample discrimination power, thereby enhancing the capacity of methamphetamine profiling program (MPP) to conduct sample-sample comparisons.

Analysis of N,N‐dimethylamphetamine in wastewater – a pyrolysis marker and synthesis impurity of methamphetamine

“…Data from forensic analyses of MA seizures indicate that DMA was detected in 58% of all seizures ( n = 794) and that, when detected, its ratio to MA was generally below 0.0025 (87% of DMA‐positive seizures). These results are line with recent findings by Li et al, who quantified DMA levels in 100 MA seizures from the USA. In their work, the highest concentration reported was equal to 449 ng of DMA per mg of MA hydrochloride (equivalent to a DMA/MA ratio of 0.00056 expressed as MA freebase).…”

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 […”

UHPLC–MS/MS quantitation of porphyroxine in opium and application of porphyroxine‐acetylated products as signature markers for heroin

“…UHPLC–MS/MS has become a common technology in the forensic community for the routine analysis of trace target compounds because of its high selectivity and sensitivity in multiple reactions monitoring (MRM) mode. A few recent publications, including two from this laboratory, discussed the applicability of UHPLC–MS/MS method in drug profiling, specifically, Lurie et al on heroin profiling …”

“…A few recent publications, including two from this laboratory, discussed the applicability of UHPLC-MS/MS method in drug profiling, specifically, Lurie et al on heroin profiling. 16,17 Due to the inconsistencies in climate and cultivation practices, and varying opium poppy varieties, there are differences in the alkaloid profiles of opium from different regions. Thus, several studies have been conducted to differentiate and geo-source opium by employing multivariate analysis on the quantified amounts of these alkaloids.…”