Study: GC-MS to Investigate Toxicology Following Italy Prison Riots

A recent study done by scientists from a group of Italian universities and government offices examined three drug overdose deaths resulting from a prison riot during the initial wave of the SARS-CoV-2 pandemic. To ascertain the nature of these deaths, a comprehensive toxicological analysis was conducted. Immunochemical screening and gas chromatography-mass spectrometry (GC-MS) were used to detect a spectrum of drugs, including 3,4-Methylenedioxymethamphetamine (MDMA, commonly referred to as “ecstasy” or “Molly”), methadone, morphine, cannabis derivatives, benzodiazepines, and others. The toxicological findings revealed high concentrations of various substances in the biological fluids of the deceased inmates. The authors published their research in Frontiers in Psychology (1).

During the first wave of the SARS-CoV-2 pandemic in Italy, the first Western country to face the viral outbreak in 2020, a series of prison riots took place after some government decrees temporarily imposed restrictions on family visits . In a central Italian detention facility, a riot occurred, and national news reported that a total of fourteen detainees were injured; eight required hospitalizations, three were admitted to intensive care, and three died after raiding the infirmary and taking drugs that had been kept there (2-4).

A general search for non-volatile organic compounds in biological samples of the three dead prisoners was performed using GC-MS. The samples underwent extraction with ethyl acetate in different environments (acidic, neutral, alkaline), and the analysts employed solid-phase extraction columns (1). The results revealed that, in the cases under study, intoxication was due to a combination of substances: tramadol and mirtazapine (Case #1), methadone and mirtazapine (Case #2), and methadone, mirtazapine, and diazepam (Case #3). In Case #1, tramadol concentration values were consistent with findings reported in the literature on acute intoxication, whereas in Case #2 depressant drug concentrations were in the therapeutic range, making it possible to hypothesize synergistic effects in the cerebral nervous system. Although there are no formally known significant interactions between methadone and mirtazapine, these drugs together can both promote fatal arrhythmias (6-8). However, tramadol has been known to show a double toxic effect because of its ability to depress the respiratory function and cause serotonin syndrome, which explains the seizures it can induce; the convulsive effect could be a result of monoamine uptake inhibition caused by enantiomers (9-13). In this context, the analysts found the co-ingestion of tramadol and mirtazapine to be of note due to the latter’s noradrenergic and serotonergic effects, which result in synergistic action (14,15). Cases of acute intoxication due to tramadol and other antidepressant drugs have been documented in the past (16).

The authors noted that, regarding the limits related to toxicological examinations, GC-MS is inherently inadequate for identifying several low-dose active substances, including new psychoactive substances, despite a full scan total ion chromatogram search being conducted. Therefore, it is important to remember that the three cases were studied comprehensively, while also relying on the available circumstantial data (1).

Man in prison hold steel cage jail bars. © methaphum - stock.adobe.com

References

1. Tomassini, L.;Giuli, G.; Bottoni, E.;David, M. C.; Scendoni, R. Drug Overdose Deaths During Prison Riots and Mental States of Prisoners: A Case Study. Front. Psychiatry 2024, (13) 15, 1377995. DOI: 10.3389/fpsyt.2024.1377995

2. Caputo, F.; Gratteri, S.; Sacco, M.A.; Scalise, C.; Cacciatore, G.; Bonetta, F. et al. Covid-19 Emergency in Prison: Current Management and Forensic Perspectives. Med. Leg. J. 2020, 88, 185–186. DOI: 10.1177/0025817220923693

3. COSA INSEGNA LA RIVOLTA IN CARCERE. 2021. http://www.formatrieti.it/cosa-insegna-la-rivolta-carcere.

4. Coronavirus, carceri, ancora proteste. Tre detenuti morti a Rieti, le vittime salgono a dodici. la Repubblica 2021. https://www.repubblica.it/cronaca/2020/03/10/news/coronavirus_carceri_ancora_proteste_tre_detenuti_morti_a_rieti-250829816/.

5. De Decker, K.; Cordonnier, J.; Jacobs, W.; Coucke, V.; Schepens, P.; Jorens, P. G. Fatal Intoxication Due to Tramadol Alone: Case Report and Review of the Literature. Forensic Sci. Int. 2008, 175, 79–82. DOI: 10.1016/j.forsciint.2007.07.010

6. McCance-Katz, E. F.; Sullivan, L.; Nallani, S. Drug Interactions of Clinical Importance Among the Opioids, Methadone and Buprenorphine, and Other Frequently Prescribed Medications: A Review. Am. J. Addict. 2010, 19, 4–16. DOI: 10.1111/j.1521-0391.2009.00005.x

7. Berling, I.; Isbister, G. K. Mirtazapine Overdose is Unlikely to Cause Major Toxicity. Clin. Toxicol. Phila. Pa. 2014, 52, 20–24. DOI: 10.3109/15563650.2013.859264

8. Klein, M. G.; Krantz, M. J.; Fatima, N.; Watters, A.; Colon-Sanchez, D.; Geiger, R. M. et al. Methadone Blockade of Cardiac Inward Rectifier K+ Current Augments Membrane Instability and Amplifies U Waves on Surface ECGs: A Translational Study. J. Am. Heart Assoc. Cardiovasc. Cerebrovasc. Dis. 2022, 11, e023482. DOI: 10.1161/JAHA.121.023482

9. Chandanwale, A. S.; Sundar, S.; Latchoumibady, K.; Biswas, S.; Gabhane, M.; Naik, M.et al. Efficacy and Safety Profile of Combination of Tramadol-Diclofenac versus Tramadol-Paracetamol in Patients with Acute Musculoskeletal Conditions, Postoperative Pain, and Acute Flare of Osteoarthritis and Rheumatoid Arthritis: A Phase III, 5-day Open-Label Study. J. Pain. Res. 2014, 7, 455–463. DOI: 10.2147/JPR.S67817

10. Sonis J. Tramadol for Acute Pain: A Review of the Evidence. Am. Fam. Physician 2005, 72, 1964. https://www.proquest.com/scholarly-journals/tramadol-acute-pain-review-evidence-reply/docview/234150833/se-2

11. Hawton, K.; Ferrey, A.; Casey, D.; Wells, C.; Fuller, A.; Bankhead C, et al. Relative Toxicity of Analgesics Commonly Used for Intentional Self-Poisoning: A Study of Case Fatality Based on Fatal and Non-Fatal Overdoses. J. Affect. Disord. 2019, 246, 814–819. DOI: 10.1016/j.jad.2019.01.002

12. Ryan, N. M.; Isbister, G. K. Tramadol Overdose Causes Seizures and Respiratory Depression but Serotonin Toxicity Appears Unlikely. Clin. Toxicol. Phila. Pa. 2015, 53, 545–550. DOI: 10.3109/15563650.2015.1036279

13, Spiller, H. A.; Gorman, S. E.; Villalobos, D.; Benson, B. E.; Ruskosky, D. R.; Stancavage, M. M. et al. Prospective Multicenter Evaluation of Tramadol Exposure. J. Toxicol. Clin. Toxicol. 1997, 35, 361–364. DOI: 10.3109/15563659709043367

14. Droghe e dipendenze [Internet]. XV rapporto sulle condizioni di detenzione 2019. https://www.antigone.it/quindicesimo-rapporto-sulle-condizioni-di-detenzione/droghe-e-dipendenze/.

15. Baltieri, D. A. Predictors of Drug Use in Prison Among Women Convicted of Violent Crimes. Crim. Behav. Ment. Health CBMH 2014, 24, 113–128. DOI: 10.1002/cbm.1883

Singleton, N.; Farrell, M.; Meltzer, H. Substance Misuse Among Prisoners in England and Wales. Int. Rev. Psychiatry Abingdon Engl. 2003, 15, 150–152. DOI: 10.1080/0954026021000046092