Abstract
PurposeThe paper presents a report on the comprehensive assessment of a novel synthetic opioid (NSO) termed U-47700, and its two metabolites: N-desmethyl-U-47700 and N,N-didesmethyl-U-47700 in autopsy blood samples taken from 12 cases of fatal poisonings.MethodsThe analysis of the examined samples was based on the solid-phase extraction/liquid chromatography–electrospray ionization-tandem mass spectrometry method, which was developed in the validation process. In the quantitative analytical studies, deuterium analytes analogs were used, namely U-47700-d6 and N-desmethyl-U-47700-d3.ResultsThe validation parameters of the method were determined, including the limits of quantification on the 1 ng/mL level, calibration curves range of 1–1000 ng/ml, intra-assay precisions and accuracies of 1.1–20.2% and −18.9–9%, respectively, and inter-assay precisions and accuracies of 2.9–13.0% and -11.4–3.3%, respectively. The matrix effects and the extraction efficiencies were formed at the levels of 54.0–119% and 53.0–118%, respectively. The parent substance and its metabolites in blood samples have been shown to be relatively stable under various conditions within the 21-day study. The concentration levels demonstrated in the analyzed blood samples were: U-47700 in the range of 83–24,000 ng/mL, N-desmethyl-U-47700 in the range of 2.0–7520 ng/mL and N,N-didesmethyl-U-47700 in the range of 18–1947 ng/mL.ConclusionsThe simultaneous quantification of U-47700, N-desmethyl-U-47700 and N,N-didesmethyl-U-47700 seems very useful to confirm the cause of death and to estimate antemortem interval. To our knowledge this is the first trial to measure phase I metabolites of U-47700 in authentic human blood samples.
Highlights
New psychoactive substances (NPS) are synthetic alternatives to more traditional drugs of abuse, engineered to circumvent the existing drug control laws
The specificity of the above method was tested by the use of more than about 400 compounds, such as medicines, drugs of abuse and NPS including novel synthetic opioid (NSO)
For the first time, a report on the comprehensive assessment of an NSO termed U-47700, and its two metabolites N-desmethyl-U-47700 and N,N-didesmethyl-U-47700 in autopsy blood samples collected from 12 cases of fatal poisonings
Summary
New psychoactive substances (NPS) are synthetic alternatives to more traditional drugs of abuse, engineered to circumvent the existing drug control laws. The emergence of NPS is a global phenomenon fuelled by the growth of Internet commerce and manufacturing capacity of Asian countries [1]. As the recreational consumption of NPS has been increasing in Europe and in the world for the Department of Forensic Medicine, Jagiellonian University Medical College, Grzegórzecka 16 St., 31‐531 Kraków, Poland past decade, such compounds have proven to be quite a challenge for public health and drug policies globally [2]. While synthetic cathinones and cannabinoids continue to predominate, an increasing number of synthetic opioids including fentanyl derivatives and non-fentanyl analogs are more commonly encountered in the recreational (i.e., non-medical) drug market in Europe and elsewhere [3, 4]. Novel synthetic opioids (NSOs) are progressively more often encountered in illicit heroin and counterfeit pain pills. Many NSOs are resurrected from older biomedical literature or patent applications, but limited information is available about their biological effects [1]
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