Systematic Studies on Temperature-Dependent In Vitro Stability during Storage and Smoking of the Synthetic Cannabinoid 5F-MDMB-P7AICA

Abstract

Metabolism studies have shown that the synthetic cannabinoid (SC) 5F-MDMB-P7AICA is predominantly degraded by ester hydrolysis to 5FMDMB-P7AICA dimethyl butanoic acid. To investigate the stability of 5F-MDMB-P7AICA during storage for a certain period of time or smoking, in vitro stability tests were performed. Blood and serum samples were collected repeatedly during a toxicokinetic study using a pig model and were retested after a 5- and 12-month storage at different temperatures (−20◦C, 4◦C or room temperature (RT)). Analysis was performed using fully validated liquid chromatography–tandem mass spectrometry methods following liquid–liquid extraction and protein precipitation. One set of samples was analyzed immediately following the experiment (without storage (WS)). In the WS samples, 5F-MDMB-P7AICA and 5F-MDMBP7AICA dimethyl butanoic acid were present in every sample collected throughout the whole experiment. Analysis of the blood and serum samples stored for 5 and 12 months at −20◦C and 4◦C revealed relatively stable concentrations of the parent substance and the dimethyl butanoic acid metabolite. Regarding the samples stored at RT, the concentrations of 5F-MDMB-P7AICA decreased, while the concentrations of the hydrolysis product increased. This change could particularly be observed in samples with a high initial concentration of the analytes. A further screening of the samples stored at RT revealed no other degradation products. In conclusion, the SC 5F-MDMB-P7AICA could be detected even after 12 months of storage at RT and therefore seems to be more stable than its isomer, 5F-ADB. Regarding the smoke condensate, besides the parent compound, only trace amounts of dimethyl butanoic acid were found.