Forensic studies of deaths involving buprenorphine have shown that it is frequently associated with benzodiazepines and that asphyxia is consistently present. However, our postmortem studies conducted between 1997 and 2002 demonstrated that buprenorphine was clearly responsible for the fatal outcome in only 12% of cases. In adult rats, we confirmed the absence of effects or the presence of moderate and transient respiratory effects of high-dose buprenorphine alone and of five benzodiazepines alone at pharmacological doses. We validated, using HPLC-MS and GC-MS, specific and sensitive analytical methods to simultaneously identify and quantify buprenorphine, benzodiazepines, and their metabolites of interest in rat plasma samples. Our experimental data have thus highlighted the toxic role of flunitrazepam metabolites in the buprenorphine-benzodiazepine interaction process.
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