Cannabidiol Determination on Peripheral Capillary Blood Using a Microsampling Method and Ultra-High-Performance Liquid Chromatography Tandem Mass Spectrometry with On-Line Sample Preparation

Abstract

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 available GW-purified form of cannabidiol (Epidiolex®). A fast 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®.

UHPLC-MS/MS Analysis of Cannabidiol and Its Metabolites in Serum of Patients with Resistant Epilepsy Treated with CBD Formulations

“…TDM is of strong support in the dose-adjustment and clinical management of patients taking different anti-seizure medications (ASMs) (e.g., valproate, carbamazepine, or CBD). Though the preferred collection method is that of venous blood, yet some new easily and patients-friendly methods such that of peripheral capillary microsampling have been recently developed and effectively applied in the clinical practice for the TDM of CBD [ 17 , 18 ]. Beyond this, one of the current limitations of CBD-based treatments is that both purified and galenic preparations are available yielding high interindividual variability and even some limits in the TDM.…”

“…Previous studies have determined the levels of CBD or its metabolites in biological samples after medical cannabis consumption [ 17 , 18 , 19 , 20 , 21 , 22 ]. Although these studies were valuable, no analytical assay exists for the simultaneous determination of CBD and its main metabolites, 7-hydroxycannabidiol (7-OH-CBD), 6-α-hydroxycannabidiol (6-α–OH–CBD) and 6-β-hydroxycannabidiol (6-β–OH–CBD) in serum samples of individuals treated with CBD-based pharmaceuticals or medical cannabis.…”

A Volumetric Absorptive Microsampling Technique to Monitor Cannabidiol Levels in Epilepsy Patients

“…Moreover, a significant advantage of this less invasive and easily reproducible procedure is that it limits the discomfort caused to patients in obtaining venous samples. However, to date, the TDM of medical cannabis has few validated analytical methods on plasma (Grauwiler et al, 2007;Aizpurua-Olaizola et al, 2017;Lomonaco et al, 2018;Pigliasco et al, 2020). We used a new microsampling method for the determination of CBD blood levels in patients with drug-resistant epilepsy using VAMS, which had previously proven useful for quantitative measurement of several venous and capillary blood drugs, including first and third-generation antiepileptic drugs (Velghe and Stove, 2018;DʼUrso et al, 2019), antibiotics (Barco et al, 2017) and immunosuppressants (Koster et al, 2019).…”

“…Moreover, a significant advantage of this less invasive and easily reproducible procedure is that it limits the discomfort caused to patients in obtaining venous samples. However, to date, the TDM of medical cannabis has few validated analytical methods on plasma ( Grauwiler et al, 2007 ; Aizpurua-Olaizola et al, 2017 ; Lomonaco et al, 2018 ; Pigliasco et al, 2020 ).…”

“…The 30 µl VAMS devices (MITRA ® , Neoteryx, Torrance, CA, United States) were used to collect venous and capillary blood. The venous VAMS samples were obtained from blood collected by ethylenediaminetetraacetic acid tubes, as described ( Barco et al, 2018 ; Pigliasco et al, 2020 ). Capillary VAMS were obtained following the manufacturer’s instructions: before pricking the patient’s finger with a microneedle, the area was disinfected and after the first drop of blood was removed, the VAMS tip was placed in contact with the surface of the second drop to adsorb the matrix.…”