Benzodiazepines enhance GABA-A signaling and are used as sedative-hypnotic, anxiolytic, and anticonvulsant agents. They are relatively safe alone but potentiate opioid-induced respiratory depression and contribute to many polydrug deaths.¹ Immunoassay screens detect the class but often miss clonazepam and lorazepam, so LC-MS/MS is needed to identify the specific agent.²

Benzodiazepines frequently contribute to fatal overdoses when combined with opioids and alcohol.² Point-of-care immunoassays that detect only the drug class can miss clinically important agents such as clonazepam and lorazepam, so a class-level negative can be falsely reassuring.³

Immunoassays detect the benzodiazepine class but vary in sensitivity and often miss clonazepam and lorazepam. LC-MS/MS identifies specific parent drugs and metabolites (e.g., alpha-hydroxyalprazolam, 7-aminoclonazepam), including after enzymatic hydrolysis of glucuronides.³ Shared metabolites (oxazepam, temazepam, nordiazepam) mean a positive may not identify which benzodiazepine was taken.⁴

• Do not rely on a benzodiazepine immunoassay to rule out clonazepam or lorazepam; order LC-MS/MS.
• Recognize shared metabolites: oxazepam, temazepam, and nordiazepam can arise from several parent drugs.⁴
• Interpret prolonged positives in chronic users of diazepam or chlordiazepoxide, which accumulate in fat and persist for weeks.
• Consider altered metabolism (CYP inhibitors or inducers, poor metabolizers) when results are unexpected.
• Assess concurrent opioid and alcohol use given additive respiratory risk.