Pharmacokinetic study of the synthetic cannabinoid, 5F-MDMB-PICA, in male Wistar rats.

Background: This research focused on establishing a highly sensitive and reliable gas chromatography-mass spectrometry (GC-MS) method for detecting and quantifying 5F-MDMB-PICA in rat plasma, as well as thoroughly assessing its pharmacokinetic characteristics, such as plasma half-life and volume of distribution.

Material and methods: Male Wistar rats were orally administered 5F-MDMB-PICA at two concentrations: 5 mg/kg and 50 mg/kg body weight. Following administration, blood samples were collected for pharmacokinetic analysis. To optimize analyte recovery and minimize matrix effects, plasma samples were subjected to a dual extraction protocol combining liquid-liquid extraction and protein precipitation. The processed samples were subsequently analyzed using GC-electron ionization/MS.

Results: The analytical method was validated in accordance with Food and Drug Administration guidelines, demonstrating excellent selectivity and robust calibration curves over a concentration range of 0.5-1000 ng/mL, exhibiting linearity with a correlation coefficient (R2) of 0.99. The limit of quantitation (LOQ) was established at 10 ng/mL. Interassay precision, expressed as relative standard deviation (RSD%), ranged from 2.54% to 3.94%, while interassay accuracy (bias%) was maintained at 9.44% for the analyte. Subsequently, the validated method was successfully applied to pharmacokinetic profiling of 5F-MDMB-PICA in rat plasma. Following oral administration, 5F-MDMB-PICA was rapidly absorbed, with a plasma half-life (t1/2) spanning 14.82-26.16 h. The volume of distribution (Vd) ranged from 86.43 to 205.39 L, and plasma clearance rates were measured between 2.28 and 9.60 L/h.

Conclusions: A precise and accurate GC-MS method was successfully developed and validated for the quantification of 5F-MDMB-PICA in rat plasma, enabling comprehensive assessment of its pharmacokinetics, bioavailability, and tissue distribution. These results provide valuable insights that may enhance the understanding of the pharmacokinetic and pharmacodynamic profiles of 5F-MDMB-PICA.