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Purpose <p>The presence of 2-benzylbenzimidazole-derived opioids (nitazenes) in the drug market is steadily increasing. These often highly potent synthetic opioids can cause severe, potentially fatal effects. This case report presents a fatal intoxication following the vaping of the novel synthetic opioid <i>N</i>-pyrrolidino protonitazene (protonitazepyne), detected in serum obtained 10&#xa0;h postmortem and in multiple specimens collected at autopsy three days after death.</p> Methods <p>Concentrations of <i>N</i>-pyrrolidino protonitazene in postmortem serum, heart blood, femoral blood, liver, bile, and stomach contents were determined using liquid chromatography–tandem mass spectrometry (LC–MS/MS) with a standard addition approach. Urine and serum were additionally analyzed via LC–MS/MS using external matrix calibration.</p> Results and discussion <p><i>N</i>-Pyrrolidino protonitazene was detected at 3.8 ng/mL in postmortem serum, 1.7 ng/mL in heart blood, approx. 0.52 ng/mL in femoral blood, 0.34 ng/g in liver, 32.3 ng/mL in bile, and 19.7 ng/mL in stomach contents. Urine contained 8.8 ng/mL. Additional findings in postmortem serum included pregabalin (7.2&#xa0;µg/mL), sertraline (66 ng/mL), naloxone (10.2 ng/mL), mitragynine (11.5 ng/mL), and traces of quetiapine. These co-ingestants did likely not account for the fatal outcome. With an estimated in vitro potency approximately 25-fold greater than fentanyl, even low doses of N-pyrrolidino protonitazene can be lethal. Elevated heart-to-femoral blood ratios indicate postmortem redistribution, while declining levels over time may indicate compound instability.</p> Conclusion <p>Due to its high potency, <i>N</i>-pyrrolidino protonitazene is considered the primary cause of death. Accordingly, a toxicological significance score of 3 is assigned, underscoring the potential public health risk posed by this novel synthetic opioid.</p>

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A case of fatal intoxication with the novel synthetic opioid N-pyrrolidino protonitazene

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年10月18日

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  • Sophia Wrbas,
  • Tom R. Sundermann,
  • Volker Auwärter,
  • Laura M. Huppertz

摘要

Purpose

The presence of 2-benzylbenzimidazole-derived opioids (nitazenes) in the drug market is steadily increasing. These often highly potent synthetic opioids can cause severe, potentially fatal effects. This case report presents a fatal intoxication following the vaping of the novel synthetic opioid N-pyrrolidino protonitazene (protonitazepyne), detected in serum obtained 10 h postmortem and in multiple specimens collected at autopsy three days after death.

Methods

Concentrations of N-pyrrolidino protonitazene in postmortem serum, heart blood, femoral blood, liver, bile, and stomach contents were determined using liquid chromatography–tandem mass spectrometry (LC–MS/MS) with a standard addition approach. Urine and serum were additionally analyzed via LC–MS/MS using external matrix calibration.

Results and discussion

N-Pyrrolidino protonitazene was detected at 3.8 ng/mL in postmortem serum, 1.7 ng/mL in heart blood, approx. 0.52 ng/mL in femoral blood, 0.34 ng/g in liver, 32.3 ng/mL in bile, and 19.7 ng/mL in stomach contents. Urine contained 8.8 ng/mL. Additional findings in postmortem serum included pregabalin (7.2 µg/mL), sertraline (66 ng/mL), naloxone (10.2 ng/mL), mitragynine (11.5 ng/mL), and traces of quetiapine. These co-ingestants did likely not account for the fatal outcome. With an estimated in vitro potency approximately 25-fold greater than fentanyl, even low doses of N-pyrrolidino protonitazene can be lethal. Elevated heart-to-femoral blood ratios indicate postmortem redistribution, while declining levels over time may indicate compound instability.

Conclusion

Due to its high potency, N-pyrrolidino protonitazene is considered the primary cause of death. Accordingly, a toxicological significance score of 3 is assigned, underscoring the potential public health risk posed by this novel synthetic opioid.