LC-MS/MS Confirms Fatal Oral Fentanyl Patch Misuse

Fentanyl is a major cause of the worldwide opioid crisis because it is extremely powerful and highly addictive. Japan has traditionally had very low rates of opioid addiction, but prescription drugs being taken by people they were not prescribed for has become a growing concern, especially among teenagers and young adults. A team of Japanese researchers published an article in the journal Legal Medicine¹ which describes a fatal overdose in which a person deliberately chewed or swallowed a fentanyl skin patch, a medication designed to be worn on the skin and release the drug slowly. Liquid chromatography–tandem mass spectrometry (LC–MS/MS) was used to determine fentanyl concentrations in the deceased’s peripheral blood and heart serum.

Why Is Fentanyl Misuse a Growing Concern in Japan?

Fentanyl is a man-made opioid that is roughly 50 to 100 times stronger than morphine. It holds a contradictory place in modern medicine: it's essential for treating severe cancer pain and pain during and after surgery, yet it is now the leading cause of opioid deaths around the world. In North America, illegally made fentanyl and similar drugs have fueled wave after wave of overdose deaths, overtaking both prescription painkillers and heroin as the main cause of fatal overdoses.^2-4

Japan, on the other hand, has long had one of the lowest rates of opioid use among wealthy countries, and it has largely escaped the heroin epidemics that have shaped drug policies in the West. Even so, a different problem has been growing at home: prescription medicines, including opioids, are increasingly being misused, often by teenagers and young adults. The misuse of mind-altering drugs by young people has become a serious and growing concern for investigators in Japan.^5-9

What Happened in This Case, and What Caused the Death?

In the case described in the article, a teenager in their late teens, who had a history of depression and gender incongruence, was found dead at home. They had no history of long-term pain and had not been prescribed opioids. An autopsy found five cut-up pieces of a fentanyl skin patch in their stomach. Laboratory testing of their blood found high levels of fentanyl, along with norfentanyl, the substance the body produces when it breaks fentanyl down. Investigators also found high levels of pregabalin, a medication used for nerve pain and anxiety. Together, the patch pieces in the stomach and the blood test results pointed to a fatal overdose from swallowing the patch. However, the researchers were careful in interpreting how much fentanyl the body had broken down, since drug levels can shift around the body after death. They concluded that because the teenager's body was not used to opioids, and because pregabalin and a type of sedative were also present, all of which slow down the brain and breathing, these factors likely added to the fatal outcome.¹

“This case,” write the authors of the paper,¹ “highlights the risks associated with high-potency opioid diversion and abusive routes of administration in psychologically vulnerable young people.”

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References

1. Miura, H.; Miyao, M.; Furukawa, S. et al. Fatal Oral Ingestion of a Sectioned Transdermal Fentanyl Patch in an Opioid-naïve Youth with Gender Incongruence: A Forensic Case Report from Japan. Leg Med (Tokyo) 2026, 87, 103018. DOI: 10.1016/j.legalmed.2026.103018
2. Armenian, P.; Vo, K. T.; Barr-Walker, J. et AL. Fentanyl, Fentanyl Analogs and Novel Synthetic Opioids: A Comprehensive Review. Neuropharmacology 2018, 134 (Pt A), 121-132. DOI: 10.1016/j.neuropharm.2017.10.016
3. Comer, S. D.; Cahill, C. M. Fentanyl: Receptor Pharmacology, Abuse Potential, and Implications for Treatment. Neurosci Biobehav Rev. 2019, 106, 49-57. DOI: 10.1016/j.neubiorev.2018.12.005
4. Friedman, J.; Shover, C. L. Charting the Fourth Wave: Geographic, Temporal, Race/Ethnicity and Demographic Trends in Polysubstance Fentanyl Overdose Deaths in the United States, 2010-2021. Addiction 2023, 118 (12), 2477-2485. DOI: 10.1111/add.16318
5. Jayawardana, S.; Forman, R.; Johnston-Webber, C. et al. Global Consumption of Prescription Opioid Analgesics Between 2009-2019: A Country-level Observational study. EClinicalMedicine 2021, 42, 101198. DOI: 10.1016/j.eclinm.2021.101198
6. Onishi, E.; Kobayashi, T.; Dexter, E. et al. Comparison of Opioid Prescribing Patterns in the United States and Japan: Primary Care Physicians' Attitudes and Perceptions. J Am Board Fam Med. 2017, 30 (2), 248-254. DOI: 10.3122/jabfm.2017.02.160299
7. Takasusuki, T.; Hayashi, S.; Koretaka, Y. et al. Prevalence of and Risk Factors for Prescription Opioid Misuse, Abuse, Diversion and Doctor Shopping in Japan: A Survey Study. Pain Ther. 2022, 11 (3), 987-1009. DOI: 10.1007/s40122-022-00409-6
8. Shimane, T.; Inoura, S.; Kitamura, M. et al. Prevalence of Over-the-Counter Drug Abuse and Associated Psychosocial Factors Among High School Students: A Nationwide Cross-Sectional Survey in Japan. Neuropsychopharmacol Rep. 2025, 45 (2), e70030. DOI: 10.1002/npr2.70030
9. Natori, Y.; Miura, H.; Yoshimoto, T. et al. Evaluation of Various Internal Standards for Quantification of Dextromethorphan and Diphenhydramine in Plasma: A Fatal Overdose Case of a Mid-teenager Caused by Personally Imported and Over-the-counter Medicines. Forensic Toxicol. 2026, 44 (1), 86-95. DOI: 10.1007/s11419-025-00736-1