Abstract
Detection of new psychoactive substances and synthetic opioids is generally performed by means of targeted methods in mass spectrometry, as they generally provide adequate sensitivity and specificity. Unfortunately, new and unexpected compounds are continuously introduced in the illegal market of abused drugs, preventing timely updating of the analytical procedures. Moreover, the investigation of biological matrices is influenced by metabolism and excretion, in turn affecting the chance of past intake detectability. In this scenario, new opportunities are offered by both the non-targeted approaches allowed by modern UHPLC-HRMS instrumentation and the investigation of hair as the matrix of choice to detect long-term exposure to toxicologically relevant substances. In this study, we present a comprehensive and validated workflow that combines the use of UHPLC-QTOF-HRMS instrumentation with a simple hair sample extraction procedure for the detection of a variety of fentanyl analogues and metabolites. A simultaneous targeted and untargeted analysis was applied to 100 real samples taken from opiates users. MS and MS/MS data were collected for each sample. Data acquisition included a TOF-MS high-resolution scan combined with TOF-MS/MS acquisition demonstrating considerable capability to detect expected and unexpected substances even at low concentration levels. The predominant diffusion of fentanyl was confirmed by its detection in 68 hair samples. Other prevalent analogues were furanylfentanyl (28 positive samples) and acetylfentanyl (14 positive samples). Carfentanil, methylfentanyl, and ocfentanil were not found in any of the analyzed samples. Furthermore, the retrospective data analysis based on untargeted acquisition allowed the identification of two fentanyl analogues, namely β-hydroxyfentanyl and methoxyacetylfentanyl, which were not originally included in the panel of targeted analytes.
Highlights
Electronic supplementary material The online version of this article contains supplementary material, which is available to authorized users.1186, Ioannina 45500, GreeceIn the last decade, the general situation and world distribution of drugs of abuse has evolved dramatically with the emergence of a large variety of new psychoactive substances (NPS)
The pattern of abused synthetic opioids progressed from the over-prescription of legal analgesic drugs such as hydrocodone, oxycodone, and fentanyl, to the clandestine synthesis of new fentanyl derivatives produced for the illegal market [1, 2]
The toxicological analyses dealing with the detection of NPS/novel synthetic opioids (NSO) cannot be counted within such an ideal scenario
Summary
Fentanyl and its analogues are considered risky for their extreme pharmacological effects, as the large and ever-increasing outburst of lethal overdose cases in the USA clearly evidences [3]. One of the challenges in the development of validated methods for the analysis and identification of NSO within a rapidly changing and dynamic market is that analytical reference materials may not be commercially available or require long time to be synthesized. Preliminary HRMS-based approaches have been recently proposed, in order to screen for different classes of drugs in hair [8], for fentanyl analogues in blood [18], or for emerging synthetic cannabinoids [19]. The untargeted investigation based on a retrospective data analysis proved qualified to perform untargeted screening without the need of analytical standards
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