Combined Use of Flubromazepam and Stimulants: Blood and Oral Fluid Concentrations and Impact on Driving Ability

Abstract

"Designer" benzodiazepines (DBZDs) are becoming increasingly available in Europe, with the European Monitoring Centre of Drugs and Drug Addiction currently monitoring ∼30 new benzodiazepines. The following driving under the influence of drug (DUID) case describes the oral fluid (OF) and blood concentrations, as well as the observed effects after the combined use of stimulants and flubromazepam. Both OF, collected via the Intercept i2 collector (Immunalysis, Pomona, CA, USA), and blood (collected in containers with various stabilizers) were screened using a liquid chromatographic (LC) time-of-flight (TOF) mass spectrometric (MS-MS) method. In addition, various LC-MS-MS methods in multi-reaction monitoring mode were applied for confirmation and quantification. The OF and blood samples were taken 2 h 25 min and 9 h 19 min after the accident, respectively. OF contained 789 ng/mL amphetamine, 5,173 ng/mL MDMA, 168 ng/mL benzoylecgonine, 492 ng/mL cocaine, 134 ng/mL 4-methylmethcathinone (4-MMC) and traces of flubromazepam (less than limit of quantification (LLOQ); 2 ng/mL). The sodium-fluoride blood samples contained 19 ng/mL amphetamine, 284 ng/mL MDMA, 20 ng/mL MDA, 38 ng/mL benzoylecgonine, 4 ng/mL methylecgonine, 161 ng/mL flubromazepam and traces of 4-MMC (<LLOQ; 2.5 ng/mL). The driver was observed to have an irregular speed driving pattern and could not keep his lane. He demonstrated the following effects after the accident: bloodshot eyes, red face, sweating, fatigue, disorientation in time and space and mental confusion. Even 24 h after the accident, the driver was confused, disoriented, had red spots on his face and could not keep his balance. The effects of flubromazepam combined with several stimulants are demonstrated. Moreover, this case illustrates well the pros and cons of the different biological matrices applied in a DUID context. Differences between the biological matrices are not only observed concerning the ease/practicality of (on-site) collection, but also in the final drug detectability due to the large variations in OF/blood drug concentration ratios and metabolism/elimination rates as a result of the different chemical entities of the compounds.