Flualprazolam distribution in postmortem samples

Abstract

The constant emergence of novel psychoactive substances is troubling to both public health officials and legislators. Additionally, sufficient data collection for each new compound can take months up to years. Flualprazolam, a triazolobenzodiazepine, quickly garnered attention as a sedative drug that likely expresses adverse reactions similarly to alprazolam. This study focuses on the distribution of flualprazolam in multiple common postmortem matrices. Central blood, vitreous humor, liver homogenate, brain homogenate, gastric contents, and urine samples from death investigation cases were quantitated when available. Samples were screened with liquid chromatography quadrupole time-of-flight with limit of detection set at 4 ng/ml and quantitated on liquid chromatography tandem mass spectrometry, with concentration range from 4 to 256 ng/ml. From August 2018 to September 2020, 24 central blood samples were quantitated for flualprazolam. Central bloods of 22 cases had concentrations above the limit of quantitation. The average flualprazolam central blood concentration was 16.3 ng/ml with a median of 9.95 ng/ml (4.24-48.0). Additional analyses for unconjugated flualprazolam were performed on at a total of 15 urine samples ( $\overline{x}$ = 14.4, 4.07-36.1 ng/ml), 23 brain homogenates ( $\overline{x}$ = 23.2, 3.99-69.3 ng/g), 23 liver homogenates ( $\overline{x}$ = 50.7, 13.6-156 ng/g), five vitreous humor samples ( $\overline{x}$ = 7.70, 4.03-12 ng/ml), and 12 gastric contents samples ( $\overline{x}$ = 0.36, 0.02-2.51 mg). The cause of death for 13 of the 24 cases listed flualprazolam as a contributing factor of death.

Keywords: benzodiazepine; flualprazolam; forensic; novel psychoactive substances; postmortem; toxicology.