Cannabidiol (CBD) has multiple therapeutic benefits that need to be maximized by optimizing its bioavailability. Numerous formulations are therefore being developed and their pharmacokinetics need to be studied, requiring analytical methods and data from intravenous administration. As CBD is susceptible to hepatic metabolism, the requirement of any method is to quantify metabolites such as 7-COOH-CBD. We demonstrated that CBD and 7-COOH-CBD could be simultaneously and correctly quantified in piglet plasma by using an UHPLC–MS/MS technique. The validated method allowed for an accurate bioanalysis of an intravenously injected solution consisting of CBD-HPβCD complexes. The experimental pharmacokinetic profile of CBD showed multi-exponential decay characterized by a fast apparent distribution half-life (0.25 h) and an elimination half-life of two hours. The profile of 7-COOH-CBD was not linked with the first-pass metabolism, since 80% of the maximum metabolite concentration was reached at the first sampling time point, without any decrease during the period of study. A two-compartment model was optimal to describe the experimental CBD profile. This model allowed us to calculate macro–micro constants and volumes of distribution (V_ss = 3260.35 ± 2286.66 mL) and clearance (1514.5 ± 261.16 mL·h⁻¹), showing that CBD is rapidly distributed to peripheral tissues once injected and slowly released into the bloodstream.

Within the family of serotonin (5-HT) receptors, the 5-HT_1A subtype is particularly interesting as it may be involved in various physiological processes or psychological disorders. The p-[¹⁸F]MPPF, a highly selective 5-HT_1A antagonist, is used for in vivo studies in human or animal by means of positron emission tomography (PET) [1]. In order to selectively extract p-[¹⁸F]MPPF and its main metabolites from plasma, molecularly imprinted polymer (MIP) was prepared against these compounds by using the p-MPPF as template. For the control of the selectivity, non-imprinted polymer (NIP) was also synthesized without template. The MIP sorbent, packed in disposable extraction cartridges (DECs), was then evaluated as molecularly imprinted solid-phase extraction (MISPE) prior to the LC determination. The conditions of extraction were evaluated in order to obtain the highest selective retention of the p-[¹⁸F]MPPF and its metabolites on this MIP. The MIP selectivity was exploited in the loading and washing steps by adjusting the pH of plasma samples at a suitable value and by selecting mixtures for the washing step to limit the contribution of non-specific interactions. Other important parameters involved in the conditioning and elution steps were also studied. Finally, a pre-validation was carried out with optimal extraction conditions to demonstrate the performance of this MISPE-LC method as a generic method in the context of evaluation of new MISPE for p-[¹⁸F]MPPF and its potential for metabolites extraction from human plasma.

Background: Cannabidiol (CBD) shows interesting therapeutic properties but has yet to demonstrate its full potential in clinical trials partly due to its low solubility in physiologic media. Two different formulations of CBD (amorphous and lipid-based) have been optimized and enable an increase in bioavailability in piglets. In vivo studies are time-consuming, costly and life-threatening. Therefore, we need to develop in vitro tests that can predict what will happen in vivo. Methods: Comparisons in terms of dissolution were made especially by using different media (FaSSGF, FaSSIF, FeSSIF, HCl 0.1N with or without SLS, phosphate buffer pH 6.8 with or without SLS) and different conditions (sink or non-sink conditions). These in vitro results were confronted with in vivo results to select the most appropriate dissolution test conditions. Results: The importance of the presence of surfactants to enable solubilization of CBD was demonstrated. Neutral media enabled a relatively good prediction of the extent of absorption observed in vivo, whereas the rate of absorption was more complicated to predict. Conclusions: FeSSIF media, and FaSSIF sink media to a lesser extent, were the only compositions enabling predictions of both extent and rate, indicating that emulsification is possibly a major contributor to the in vivo availability of the drug.