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Benzodiazepines are widely used in the treatment of sleep and anxiety disorders, as well as epileptic seizures and alcohol withdrawal because of their broad therapeutic index and low cost. Due to their central nervous system depressant effects they are also often implicated in traffic accidents and drug-related intoxications. With the increasing number of designer benzodiazepines used in a recreational setting, there is a need for analytical methods able to quantify both the prescribed and designer benzodiazepines. A liquid chromatography–triple quadrupole mass spectrometry method was developed for the quantification of 34 prescribed and 20 designer benzodiazepines in plasma. Different sample preparation strategies, including protein precipitation, liquid-liquid extraction, solid-phase extraction and mini-QuEChERS, were tested. The best recoveries for all compounds of interest were obtained with a liquid-liquid extraction using methyl-tertiary-butyl-ether and 500 μL plasma. The method was fully validated according to the European Medicines Agency guidelines for all compounds, except pivoxazepam, which is included for qualitative purposes only. In-sample stability issues were observed for cloxazolam, both at ambient temperature and during long-term storage at −20 °C. Due to the large number of compounds included, the simple and time-efficient sample preparation, and the relatively inexpensive instrumentation used, the presented method can be readily implemented in both therapeutic drug monitoring and forensic analyses.

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Toxicological data on overdose with HIV-inhibitors is scarce. We present a case report of two independent suicide attempts by self-administered overdose with the same antiretroviral medicine Genvoya® (emtricitabine/elvitegravir/tenofovir alafenamide/cobicistat). Both patients were admitted to the hospital and presented with a loss of consciousness, lactic acidosis, elevated hepatic transaminase levels and hemodynamic instability. While one patient survived with advanced supportive measures, the other passed away. Emtricitabine levels were measured in vivo in various consecutive serum samples and post-mortem urine, peripheral and cardiac serum samples and confirmed excessive use in both cases. This is the first time emtricitabine levels following overdose are reported. Although measured concentrations for emtricitabine were quite similar in these cases, metabolic acidosis was more pronounced in the fatal case. The difference in outcome between the two could be due to a difference in physiological status, susceptibility to accumulation and adverse effects, and perhaps a varying interval between ingestion and the start of supportive measures.