Application of Fabric Phase Sorptive Extraction (FPSE) Engaged to Tandem LC-MS/MS for Quantification of Brorphine in Oral Fluid

Brorphine (1-[1-[1-(4-bromophenyl) ethyl]-piperidin-4-yl]-1,3-dihydro-2H-benzo [d]imidazol-2-one) is one of the most recent novel synthetic opioids (NSOs) on the novel psychoactive substances (NPSs) market, involved in over 100 deaths in 2020. Brorphine is a substituted piperidine-benzimidazolone analogue that retains structural similarities to fentanyl, acting as a full agonist at the μ-opioid receptor. Oral Fluid (OF) is an alternative matrix, frequently analyzed for the detection of NPS. Fabric phase sorptive extraction (FPSE) is a superior, green-sample -preparation technology recently applied for drug analysis. This contribution presents the development and validation of a method, based on the application of FPSE and liquid chromatography–tandem mass spectrometry (LC-MS/MS), to determine/quantitate brorphine in OF. The method’s linearity ranged between 0.05 and 50 ng/mL (R(2) = 0.9993), the bias ranged between 12.0 and 16.8%, and inter- and intra-day precisions ranged between 6.4 and 9.9%. Accuracy and extraction efficiency lied between 65 and 75%. LOD/LOQ were 0.015 ng/mL/0.05 ng/mL. Analyte’s post-preparative stability was higher than 95%, while no matrix interferences and carryover between runs were observed. This is the first report introducing the application of FPSE for NPS determination, specifically, the quantification of brorphine in OF, thereby presenting a simple, rapid, sensitive, specific, effective, and reliable procedure engaged to LC-MS/MS that is suitable for routine application and the analysis of more NPSs.