Evaluation of the in-vitro inhalation uptake of MDMB-4en-PINACA using a smoking simulation chamber

Synthetic cannabinoids are typically sold as herbal smoking mixtures impregnated with psychoactive substances, being the main route of administration through smoking inhalation. In this study, a simulation chamber has been designed for the estimation of the inhalation uptake of synthetic cannabinoids during conventional herb smoking using a dedicated smoking machine. MDMB-4en-PINACA was selected as model compound because of it was one of the most popular synthetic cannabinoids in the late 2020. Silicone tube and Gamble's solution were employed as simulants of human trachea and interstitial lung fluids, respectively. Simulants were extracted with methanol and the obtained extracts were analysed by liquid chromatography-fluorescence detection with a limit of detection of 0.7 mu g L-1. The percentage of lung inhalation uptake was significative, ranged from 24.5 to 34.1 % of the MDMB-4en-PINACA vaporized amount. Moreover, MDMB-4en-PINACA thermal degradation products were identified by liquid chromatography-high resolution tandem mass spectrometry and a major thermolytic pathway was proposed. Thus, the developed smoking simulation chamber is a versatile tool that allows the rapid and simple estimation of the inhalation uptake of synthetic cannabinoids during smoking.