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 5F-MDMB-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-MDMB-P7AICA 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.