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

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. 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. 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. 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.