Otimização e validação de método bioanalítico para determinação do canabidiol em plasma e obtenção de parâmetros farmacocinéticos em diferentes modelos animais

Abstract

It has dozens of substances called phytocannabinoids, including cannabidiol, a non-psychoactive phytocannabinoid with several therapeutic activities described.. In this sense, the objective of this work was to develop a reliable, economical and robust bioanalytical method to evaluate the pharmacokinetic parameters of cannabidiol in plasma of Wistar rats and dogs. The samples were then evaporated and reconstituted in methanol and formic acid and injected into an HPLC system. Separation was performed using an ACE® C18 column (100 mm × 4.0 mm, 5 μm) at 35 ◦C with isocratic elution using an aqueous phase A (10 mM ammonium formate) and an organic phase B (0.1% methanol/formic acid) (10:90 v/v) under a flow rate of 0.6 mL/min and injection volume of 10 μL. This new method showed linearity in the range of 1–5,000 ng/mL and a lower limit of quantification (LLOQ) of 1 ng/mL, which is comparable to the previously reported LC–MS/MS methods. Inter- and intraday precision and accuracy were less than 15% of DSR and DO, respectively. To demonstrate the suitability of the method for in vivo studies in rats, the assay was applied to a preliminary pharmacokinetic study following IV administration of 10 mg/kg CBD and 20 mg/kg orally. Pharmacokinetic analysis revealed the following: t1/2 CBD, 4.56 h (i.v.) and 3.27 h (p.o). The mean absorption time of oral CBD was 0.08 h, indicating that injectable CBD is primarily absorbed within one hour. Clearance (CL) and volume of distribution (Vd) were 4.8 L·h−1 kg−1 and 33.3 L·kg−1. In conclusion, a simple, sensitive, and cost-effective LC/MS-MS method for CBD determination has been developed, validated, and successfully applied to a pharmacokinetic study in rats.