An Ultrafast Ultrahigh-Performance Liquid Chromatography Coupled With Tandem Mass Spectrometry Method for Cannabidiol Monitoring in Pediatric Refractory Epilepsy

Abstract

Background: Cannabidiol (CBD) is a nonpsychoactive natural product that has been increasingly used as a promising new drug for the management of neurological conditions such as refractory epilepsy. Development of rapid and sensitive methods to quantitate CBD is essential to evaluate its pharmacokinetics in humans, particularly in children. The objective of this work was to develop and validate an ultrafast ultrahigh-performance liquid chromatography coupled with tandem mass spectrometry (UHPLC-MS/MS) method for CBD quantitation that is capable of detecting major CBD and tetrahydrocannabinol (THC) metabolites in the plasma of pediatric refractory epilepsy patients.Methods: Eight-point CBD calibration curves were prepared using 60 mL of plasma from healthy volunteers. Samples were analyzed in a Shimadzu Nexera X2 UHPLC system, which was coupled to a Sciex QTRAP 6500 mass spectrometer. Chromatography was optimized in acetonitrile (ACN)/water with a 70%-90% gradient of ACN in 2 minutes. Multiple reaction monitoring transitions of major CBD and THC metabolites were optimized in patient plasma. Results:The optimized UHPLC-MS/MS method was validated for the linear range (1-300 ng/mL) of CBD (r 2 = 0.996). The limit of quantification and limit of detection were 0.26 and 0.86 ng/mL, respectively. Accuracy and precision met the acceptable validation limits. CBD recovery and matrix effects were 83.9 6 13.9% and 117.4 6 4.5%, respectively. The method was successfully applied to quantify CBD and detect the major CBD and THC metabolites in clinical samples. 7-COOH-CBD was the most intensely detected metabolite followed by glucuronide conjugates.Conclusions: A simple and sensitive method for rapidly monitoring CBD and identifying relevant metabolites was developed. Its applicability in samples from children treated for epilepsy was demonstrated, making it an excellent alternative for performing pharmacokinetic studies.

On-Line Solid Phase Extraction High Performance Liquid Chromatography Method Coupled With Tandem Mass Spectrometry for the Therapeutic Monitoring of Cannabidiol and 7-Hydroxy-cannabidiol in Human Serum and Saliva

“…Several assays for determining CBD in different biological matrices such as peripheral capillary blood, plasma, serum, saliva, urine, breast milk and hair have been reported recently ( Pérez Montilla et al, 2021 ; Sempio et al, 2021b ; Cliburn et al, 2021 ; da Silva et al, 2020 ; Desrosiers et al, 2015 ; Cobo-Golpe et al, 2021 ; Reber et al, 2021 ). Although a few of these assays have also been validated for measuring the active metabolite 7-hydroxy-CBD in plasma or serum samples ( Sempio et al, 2021a ; Malaca et al, 2021 ), to our knowledge the present HPLC-MS/MS method is the first reported assay that permits the simultaneous determination of CBD and its active metabolite 7-hydroxy-CBD in both human serum and saliva.…”

evaluación de desempeño del servicio de dosificación de precisión para vancomicina en un hospital pediátrico de nivel terciario

“…y publicaciones de investigaciones (siempre asociadas a temas de farmacocinética y farmacología clínica, aunque no solo de antibióticos), observamos un incremento sostenido a lo largo del período evaluado (cantidad media de presentaciones por año, por período: 4 en 2007-2010 vs 7 en 2011-2020). En este sentido, el cambio más relevante se produjo en relación a la importancia, medida en términos del factor de impacto de las revistas en la que fueron publicados estos trabajos, correspondiendo los de la última etapa a revistas de mayor factor de impacto en relación al primer período (26)(27)(28)(29) . Asimismo, las actividades de formación de recursos humanos en ámbitos profesionales, incluyendo a universidades, sociedades científicas y demás instituciones de similar envergadura, también mostraron un incremento constante (cantidad media de actividades docentes por año, por período: 5 en 2007-2010 vs 11 en 2011-2020).…”

Real-World Evidence of Factors Affecting Cannabidiol Exposure in Children with Drug-Resistant Developmental and Epileptic Encephalopathies

“…Quantification of CBD was performed by means of a validated method using ultrahigh-performance liquid chromatography coupled with tandem mass spectrometry (UHPLC-MS/MS) as previously reported. The assay was linear in the range of 1–300 ng/mL, the lower limit of quantification for CBD was 0.9 ng/mL, and intra-day precision was >96% [ 21 ].…”