Authors: (including presenting author): :
Yeung CW (1)(2), Tang MHY (1)(2), Tong HF (3), Ching CK (1)(2), Chong YK (1)(2)
Affiliation: :
(1) Hospital Authority Toxicology Reference Laboratory, Hong Kong SAR, China
(2) Chemical Pathology Laboratory, Department of Pathology, Princess Margaret Hospital, Hong Kong SAR, China
(3) Western Diagnostic Pathology, Australia
Keyword 1: :
Protonitazene
Keyword 2: :
New synthetic opioids
Keyword 3: :
Opioid toxidrome
Keyword 4: :
Mass spectrometry
Introduction: :
Nitazenes, a class of highly potent new synthetic opioids (NSO), are new psychoactive substances (NPS) gaining worldwide concern recently. An increasing number of nitazene-related intoxications and fatalities has been reported in North America and Europe. Here, we present a local cluster of unbeknownst protonitazene consumption and poisoning during a party event. Features of NPS poisoning and in vivo metabolism of protonitazene are highlighted.
Objectives: :
To diagnose new synthetic opioid poisoning with mass spectrometric analysis of biological samples.
To investigate the in vivo metabolism of protonitazene.
Methodology: :
Clinical records of the affected individuals were retrieved for review.
Biological specimens of the individuals were pretreated with glucuronidase digestion and solid-phase extraction. They were then analyzed using ultra-high performance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry (UHPLC-QTOF-MS), together with available reference standards. Data analysis was performed on the SCIEX OS software using an in-house database containing the retention time, monoisotopic mass, and MS/MS spectral library of therapeutic drugs, common drugs of abuse/NPS, and their metabolites.
Result & Outcome: :
The cluster comprised four individuals. One individual was pronounced dead before arrival to hospital, hence not within the realm of the present study. The other three individuals presented with varying severity of mixed opioid and sympathomimetic toxidrome, but their clinical histories only suggested stimulant and cannabis intake. Initial toxicology screening detected stimulants and ketamine, which failed to explain the opioid toxidrome. NSO intoxication was therefore suspected.
Search for NSO in the biological specimens of the cases revealed the parent drug protonitazene in the urine specimens of two cases, whereas metabolites of protonitazene were detected in the urine specimens of all three cases, which strongly suggested that their consumed substance had been laced with protonitazene. These findings shed light on the in vivo metabolism of protonitazene, which could facilitate future case detection. This cluster of protonitazene poisoning also displays the prototypical features of NPS intoxication, including mislabeling of consumed substance, discordant clinical picture, and the difficulty in drug detection. Hence, vigilance of frontline clinicians and laboratory personnel and their collaborative effort are vital to continue the combat against misuse of nitazenes and other NPS.
