An emerging category of chemical treat agents are synthetic opioids, like fentanyl, carfentanil and remifentanil [1].

These toxic chemicals, that target the central nervous system, have lethal doses that are comparable to traditional nerve agents. Because of its potency and wide availability, these opioids are often found at crime scenes or the cause of overdoses. In addition to establishing the nature of the agent used, addressing the question of its origin is of equal if not greater importance to accurately reconstruct events and find the persons and institutions responsible.

Chemical profiling can be applied to establish a link between material found at the crime scene and a person or location. In the field of illicit drugs, chemical attribution signatures are often impurity profiles [2]. However, after exposure it is often difficult to find intact traces of the chemical that was used. Therefore, it would be valuable if chemical attribution signatures could also be obtained from biological samples.

"After exposure it is often difficult to find intact traces of the chemical that was used."

The process in the body could be mimicked in vitro by incubation of opioid samples with human microsomes [3,4]. Subsequently, it would be valuable to identify the remaining impurities post-metabolism, which is typically analysed by analytical methods such as gas chromatography-mass spectrometry and liquid chromatography-mass spectrometry [2,5].

This literature thesis aims to identify the main metabolic pathway of carfentanil and remifentanil. In addition, relevant analytical methods are examined for identifying the compounds and the impurities which can be used for chemical profiling.

Apply for a literature thesis on this subject. You can find more information at: open_in_new clhc.nl

References

[1] J.R. Riches, R.W. Read, R.M. Black, N.J. Cooper, C.M. Timperley, Analysis of clothing and urine from Moscow theatre siege casualties reveals carfentanil and remifentanil use., J. Anal. Toxicol. 36 (2012) 647–56. https://doi.org/10.1093/jat/bks078.

[2] I.S. Lurie, A.L. Berrier, J.F. Casale, R. Iio, J.S. Bozenko, Profiling of illicit fentanyl using UHPLC-MS/MS, Forensic Sci. Int. 220 (2012) 191–196.

[3] M.G. Feasel, A. Wohlfarth, J.M. Nilles, S. Pang, R.L. Kristovich, M.A. Huestis, Metabolism of Carfentanil, an Ultra-Potent Opioid, in Human Liver Microsomes and Human Hepatocytes by High-Resolution Mass Spectrometry, AAPS J. 18 (2016) 1489–1499. https://doi.org/10.1208/s12248-016-9963-5.

[4] L. Kong, A.J. Walz, Mass spectrometric characterization of carfentanil metabolism in human, dog, and rat lung microsomes via comparison to chemically synthesized metabolite standards, Forensic Toxicol. 38 (2020) 352–364. https://doi.org/10.1007/s11419-019-00521-x.

[5] A.D. Winokur, L.M. Kaufman, J.R. Almirall, Differentiation and identification of fentanyl analogues using GC-IRD, Forensic Chem. 20 (2020) 100255. https://doi.org/10.1016/j.forc.2020.100255.