Cannabidiol determination on peripheral capillary blood using a microsampling method and ultra-high-performance liquid chromatography tandem mass spectrometry with on-line sample preparation

The aim of this work is to evaluate volumetric absorptive microsampling (VAMS) from capillary blood as an alternative strategy for therapeutic drug monitoring (TDM) in patients treated with the newly availableGW-purified form of cannabidiol (Epidiolex®). Afast ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) coupled to an online sample preparation system analysis was carried out on a Thermo Scientific Ultimate 3000 LC system coupled to a TSQ Quantiva triple quadrupole for the quantification of cannabidiol (CBD) and, in addition, delta-9-tetrahydrocannabinol (Δ9-THC). After validation using European Medicine Agency (EMA) guidelines the method was applied to samples obtained by finger prick of five pediatric patients treated with Epidiolex® and the results were compared to those obtained from venous blood and plasma. The method is linear in the range of 1-800 μg/L for both CBD and THC with intra- and inter-day precisions ranging from 5% to 14% and accuracies from -13% to +14% starting from 30 μL of sample. Stability in VAMS is ensured for up to 4 weeks at 25 °C thus allowing simple delivery. There was no difference (p = 0.69) between concentrations of CBD measured from VAMS sampled from capillary or venous blood (range: 52.19-330.14 or 72.15-383.45 μg/L) and those obtained from plasma (range: 64.3-374.09 μg/L) The VAMS-LC-MS/MS method represents a valid alternative strategy for therapeutic drug monitoring of patients treated with Epidiolex®.