Potential of High-Resolution Mass Spectrometry for the Detection of Drugs and Metabolites in Hair: Methoxetamine in a Real Forensic Case.

The analysis of drugs of abuse in hair and other biological matrices of forensic interest requires great selectivity and sensitivity. This is done traditionally through target analysis, with one or more analytical methods, or with different and specific preanalytical phases, and complex procedures performed by the toxicological laboratories, and there is no exception with ketamine-like compounds, such as methoxetamine, a new psychoactive substance whose use has increased in the last decades, and continues to grow quickly year by year. More validated methods of analysis are needed to detect these substances in low concentrations selectively. Reanalyzing the samples of a former case of a polydrug consumer accused of a crime against public health in Spain, five metabolites of methoxetamine (normethoxetamine, O-desmethylmethoxetamine, dehydromethoxetamine, dihydronormethoxetamine and hydroxynormethoxetamine) were tentatively detected using a high-resolution technique, that is, liquid chromatography coupled to high-resolution mass spectrometry (LC-HR-MS-MS). The highest analytical selectivity of LC-HR-MS-MS method together a universal and simpler pretreatment stages has demonstrated to allow faster analysis and more sensitivity than the one performed traditionally at the INTCF laboratories, which was gas chromatography coupled to mass spectrometry.

Prevalence study of drugs and new psychoactive substances in hair of ketamine consumers using a methanolic direct extraction prior to high-resolution mass spectrometry.

Few studies have reported the prevalence or incidence about the consumption of new psychoactive substances (NPS). The hair analysis can be useful for this purpose. At the present, ketamine is the most consumed arylcyclohexylamine associated to young consumers and polyconsumption profiles. For this reason, ketamine consumer cases become very interesting to provide information on NPS prevalence. In this work, ten former cases of the National Institute of Toxicology and Forensic Science (INTCF) of Madrid Department (INTCFM), all of them belonging to defendants accused of crimes against public health and who had been found positive to ketamine, were reassessed. At the first toxicological analysis of those hair samples, a positive consume in ketamine had been determined by gas chromatography coupled to mass spectrometry (GC-MS). In this work, the same hair samples were reanalyzed by high-resolution mass spectrometry ( UHPLC-HRMS/MS) using an incubation methanolic extraction combined with a single, simpler, non-selective and direct sample pre-treatment. After corroborating the GC-MS results previously obtained for the same samples, the detection of additional NPS using this new methodology evidenced its benefits and opened the possibility to perform a NPS prevalence study. In brief, in those cases with a positive consumption in ketamine, a polyconsumption of other drugs and NPS was found, including different arylcyclohexylamines as deschloroketamine, 3-MeO-PCP and methoxetamine; and cathinones as methylmetcathinone and N-ethyl-pentylone.

A validated GC-MS method for ketamine and norketamine in hair and its use in authentic cases.

This work has shown that it is a valid method for determining ketamine, norketamine and amphetamines derivates in hair samples of forensic cases. This method was validated meeting the criteria of sensitivity and accuracy for detecting repeated consumption of ketamine in hair samples of forensic interest, according to the proposed cut-off for ketamine of 0.5 ng/mg. The detection of norketamine allowed discriminating between active uses and external contamination. The assessed method was applied for analyzing 1189 hair samples of judicial interest received in the INTCF along 15 months, obtaining 62 positive in ketamine consumption. This means a 5.2% of positivity. Ketamine consumers present a profile of young age (21-30 years old), polydrug use with consumption of synthetic substances preferably MDMA and, then, amphetamine. As consumer is collective, prone to consume new psychoactive substances, requires special attention due to they show a consumer profile with higher prevalence in MDMA than amphetamine, indicating that ketamine consumers belong to a subgroup with a different profile within the INTCF casuistry. The results of the exercises of the proficiency tests performed satisfactorily in all cases. In conclusion, it is a suitable method also to evaluate the chronic consumption of ketamine, in addition to amphetamines in the same method of analysis.