Protodesnitazene: The identification and tissue distribution of a new nitazene

Abstract

Multiple new analogues from the 2-benzyl benzimidazole or "nitazene" class of drugs have emerged on the drug market in recent years. Nitazenes are highly potent μ-opioid receptor agonists that present a substantial public health concern due to their elevated risk of severe toxicity in overdose and their significant potential for misuse. We report on a case involving an overdose with another new analogue from this class, protodesnitazene. The drug has a similar potency to fentanyl and has not been previously reported in toxicology specimens or drug seizures. Protodesnitazene was initially identified by LC-QTOF-HRMS (High Resolution Mass Spectrometry) and distinguished from relevant isomers by chromatographic separation, with spectral and retention time matching against reference standards. A quantitation method employing solid phase extraction using mixed mode cartridges and utilizing LC-MS/MS operating in MRM mode was developed and partially validated for non-routine analyses. Concentrations for the parent drug were determined in a range of postmortem matrices and femoral blood levels (77-222 ng/mL) were found to be comparable to previously identified desnitazene compounds. Protodesnitazene was observed to metabolize extensively by N-dealkylation, O-dealkylation, and hydroxylation. Glucuronides were not present at high levels in the blood but were prominent in the urine. Protodesnitazene was also identified in an associated seized powder.