Brorphine and Its Analogues: Pharmacology, Toxicology, and Biomonitoring

The rise of nonfentanyl synthetic opioids such as brorphine highlights the dynamic evolution of illicit opioid markets and the persistent toxicological and public health risks they pose.

Studies reporting the pharmacology, toxicology, and analytical detection of brorphine and its analogues were identified through systematic searches of PubMed and Scopus databases. Additional data from official international organizations' early-warning platforms were also included.

Brorphine acts as a potent μ-opioid receptor agonist with preclinical evidence of strong antinociceptive activity, respiratory depression, and abuse potential. Since 2019, it has been increasingly identified in forensic casework, frequently in combination with fentanyl or benzodiazepines, and implicated in multiple nonfatal and fatal intoxications. Structurally related analogues, including halogenated derivatives and "orphine-type" compounds, whose pharmacological properties and toxicological profiles are not well understood, have emerged. Although several liquid chromatography coupled with mass spectrometry-based methods exist for brorphine detection, no validated analytical workflows or certified reference materials are currently available for its analogues, limiting comprehensive monitoring and biomonitoring capacity.

The rapid spread of brorphine and its analogues underscores the ongoing transition from fentanyl derivatives toward novel nonfentanyl μ-opioid receptor agonists. These substances pose significant analytical and toxicological challenges and require increased international surveillance, improved laboratory capabilities, and coordinated public health responses to reduce their impact.