Detection and discrimination of sedative-hypnotics in spiked beverage dry residues using attenuated total reflectance-Fourier transform infrared (ATR-FTIR) spectroscopy combined with chemometrics.

Drugs-facilitated crimes (DFCs) involve the incapacitation of victims under the influence of drugs. Conventionally, a drug administration act is often determined through the examination of biological samples; however, dry residues from any surface, such as drinking glass if related to a DFC could be a potential source of evidence. This study was aimed to establish an attenuated total reflectance-Fourier transform infrared (ATR-FTIR) spectroscopy coupled with chemometrics for the determination of spiked sedative-hypnotics from dry residues of a drug-spiked beverage. In this study, four sedative-hypnotics, namely diazepam, ketamine, nimetazepam, and xylazine were examined using ATR-FTIR spectroscopy. Subsequently, the ATR-FTIR profiles were compared and decomposed by principal component analysis (PCA) followed by linear discriminant analysis (LDA) for their detection and discrimination. Visual comparison of ATR-FTIR profiles revealed distinct spectra among the tested drugs. An initial unsupervised exploratory PCA model indicated the separation of four main sedative-hypnotics clusters, and the proposed PCA score-LDA model had allowed for a 100% accurate classification. Discrimination of sedative-hypnotics from a dry beverage previously spiked with these drugs was also possible upon an additional extraction procedure. In conclusion, ATR-FTIR coupled with PCA score-LDA model was useful in detecting and discriminating sedative-hypnotics, including those that had been previously spiked into a beverage.

Vortex-assisted dispersive liquid-liquid microextraction-gas chromatography (VADLLME-GC) determination of residual ketamine, nimetazepam, and xylazine from drug-spiked beverages appearing in liquid, droplet, and dry forms.

Presently, investigations of drug-facilitated crimes (DFCs) rely on the detection of substances extracted from biological samples following intake by the victim. However, such detection requires rapid sampling and analysis prior to metabolism and elimination of the drugs from the body. In cases of suspected DFCs, drug-spiked beverage samples, whether in liquid, droplet, or even dried form, can be tested for the presence of spike drugs and used as evidence for the occurrence of DFCs. This study aimed to quantitatively determine three sedative-hypnotics (ketamine, nimetazepam, and xylazine) from drug-spiked beverages using a vortex-assisted dispersive liquid-liquid microextraction-gas chromatography (VADLLME-GC) approach. In this study, a GC method was first developed and validated, followed by the optimization of the VADLLME protocol, which was then applied to quantify the target substances in simulated forensic case scenarios. The developed GC method was selective, sensitive (limit of detection: 0.08 µg/ml [ketamine]; 0.16 µg/ml [nimetazepam]; 0.08 µg/ml [xylazine]), linear (R2 > 0.99), precise (%RSD <7.2%), and accurate (% recovery: 92.8%-103.5%). Higher recoveries were achieved for the three drugs from beverage samples in liquid form (51%-97%) as compared to droplet (48%-96%) and dried (44%-93%) residues. The recovery was not hindered by very low volumes of spiked beverage and dried residues. In conclusion, the developed VADLLME-GC method successfully recovered ketamine, nimetazepam, and xylazine from spiked beverages that are likely to be encountered during forensic investigation of DFCs.

Heroin in Malaysia and Singapore.

Clandestine heroin laboratories have been a feature of the Malaysian illicit drug scene since soon after the abuse of heroin emerged in 1972. The first few clandestine heroin laboratories which synthesised heroin via the acetylation of imported morphine were uncovered in 1973 and 1977. By the mid-1980s, this type of laboratory was replaced by heroin-cutting laboratories whereby imported high-grade heroin was cut to street heroin. This was to meet the rising demand for the drug owing to the rapid escalation of the number of drug users. Over the years, the most significant change in the composition of the street heroin is the decrease in its purity from 30%-50% to 3%-5%. Caffeine has remained the major adulterant and chloroquine is detected in virtually all recent seizures.

Clarification of route specific impurities found in methylamphetamine synthesised using the Birch method.

This paper focuses on the determination of route specific impurities produced when methylamphetamine is synthesised using the Birch reduction. Previous work available in the scientific literature reported only one route specific impurity using ephedrine hydrochloride as the starting material. In this paper we investigated the impurity profiles of methylamphetamine produced from both the salt and base forms of ephedrine and pseudoephedrine. A new previously unreported route specific impurity was revealed as was the potential absence of the previously reported impurity in the profile of samples prepared from the free base.

Investigation of the reaction impurities associated with methylamphetamine synthesized using the Nagai method.

The synthesis of methylamphetamine hydrochloride from l-ephedrine or d-pseudoephedrine hydrochloride via reduction with hydriodic acid and red phosphorus was investigated. Eighteen batches of methylamphetamine hydrochloride were synthesized in six replicate batches using three different reaction times. This allowed the investigation of the variation of impurities in the final product with reaction time. The results obtained have resolved previously conflicting impurity profile data reported in the literature for this synthesis route. The impurity profile was shown to change with reaction time, and all previously reported impurity components were identified but not in all batches. Additionally, 20 batches of methylamphetamine hydrochloride were synthesized from either from l-ephedrine or d-pseudoephedrine hydrochloride in reactions which were allowed to proceed for 24 h. The impurities present in the resulting batches were investigated, and route-specific impurities present in all batches were identified. Batch-to-batch fluctuations in the resultant chromatographic impurity profile, despite careful synthetic monitoring and control, were also noted.

Characterization of route specific impurities found in methamphetamine synthesized by the Leuckart and reductive amination methods.

Impurity profiling of seized methamphetamine can provide very useful information in criminal investigations and, specifically, on drug trafficking routes, sources of supply, and relationships between seizures. Particularly important is the identification of "route specific" impurities or those which indicate the synthetic method used for manufacture in illicit laboratories. Previous researchers have suggested impurities which are characteristic of the Leuckart and reductive amination (Al/Hg) methods of preparation. However, to date and importantly, these two synthetic methods have not been compared in a single study utilizing methamphetamine hydrochloride synthesized in-house and, therefore, of known synthetic origin. Using the same starting material, 1-phenyl-2-propanone (P2P), 40 batches of methamphetamine hydrochloride were synthesized by the Leuckart and reductive amination methods (20 batches per method). Both basic and acidic impurities were extracted separately and analyzed by GC/MS. From this controlled study, two route specific impurities for the Leuckart method and one route specific impurity for the reductive amination method are reported. The intra- and inter-batch variation of these route specific impurities was assessed. Also, the variation of the "target impurities" recently recommended for methamphetamine profiling is discussed in relation to their variation within and between production batches synthesized using the Leuckart and reductive amination routes.