Bromazepam

The abuse of oxycodone (OC) as a “recreational” drug has increased in the last two decades the risk of fatalities. We report two drug‐related deaths in which OC intoxication was considered the cause of death. Two brothers, a 19‐year‐old male (Subject 1) and a 27‐year‐old male (Subject 2), were found dead in their bedroom, lying on their beds. They were testified as alive in the morning, both deeply sleeping and loudly snoring in their beds; they were found dead later in the afternoon. On death scene investigation, two packs of 40 mg OxyContin extended release and one alprazolam blister were found. The external examination was performed 72 h after death with the collection of blood from femoral vein, vitreous humor, and urine samples. There were no trace of injection and no external signs of injury. A complete autopsy was performed 10 days after death with the collection of peripheral blood from the femoral vein; central blood from the right ventricle; urine; gastric contents; and bile, adipose tissue, kidney, liver, brain, skeletal, and cardiac muscle tissue samples. The toxicological ascertainment evidenced the presence of OC, alprazolam, and bromazepam in fluids and tissues. For Subject 1, the concentration of OC in peripheral blood collected 72 h after death (0.33 mg/L) was similar to the concentration in vitreous humor (0.41 mg/L); vitreous humor to peripheral blood ratio was 1.24. Ten days after death, OC levels were more than 10 times higher in peripheral blood (5.14 mg/L) and about six times higher compared to central blood specimen (1.78 mg/L), while OC levels in urine were, as expected, analogous. For Subject 2, OC concentration in peripheral blood collected 72 h after death (0.50 mg/L) was similar to vitreous humor (0.87 mg/L). At Day 10 after death, OC levels were four times higher in peripheral blood (2.10 mg/L) while levels in central blood were lower (0.40 mg/L). OC concentration in urine was substantially similar at the two times of collection. OC levels in gastric contents were quite high (more than 50 mg/L). The analyses of specimens collected at two different times clearly demonstrate variation of blood OC concentrations with time. Postmortem redistribution from organs was also evidenced by high concentrations of OC in tissues such as the liver and kidney.

Rapid and comprehensive qualitative and quantitative analytical procedures are crucial in 24/7 emergency toxicology (ET) to support diagnosis and treatment of acute intoxications and to monitor their progression and efficacy of detoxification strategies. This study aimed to develop the simultaneous qualitative and quantitative analysis of 62 drugs, as well as seven active metabolites in human blood plasma using an automated liquid chromatography (LC)‐linear ion trap mass spectrometry (MS) screening system. Sample preparation was conducted by liquid–liquid extraction, and plasma concentrations were determined using an electronically stored 5‐point calibration. Validation was performed according to international guidelines and recommendations for ET including selectivity, carry‐over, accuracy, precision, and matrix effects. Finally, applicability was evaluated using case samples and proficiency tests. The method demonstrated selectivity for all analytes, with no significant carry‐over or matrix effects. Accuracy and precision recommended for ET could be fulfilled for all tested analytes, except for 10 analytes. Patient plasma samples were analyzed and compared with results obtained by reference LC‐tandem MS or gas chromatography‐MS methods. Furthermore, the applicability of the method could be demonstrated. It provides a fast, robust, and reliable blood plasma screening for 69 analytes and an additional quantification of 59 analytes relevant in ET. The use of an electronically stored 5‐point calibration and a simplified “push and print solution” allows for straightforward assessment of blood plasma levels of the analytes.