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

This database includes the raw data linked with the paper “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".

Cannabidiol is a novel antiseizure medication approved in Europe and the US for the treatment of seizures associated with Lennox-Gastaut syndrome, Dravet syndrome and tuberous sclerosis complex. We describe in this article a new and simple liquid chromatography-mass spectrometry method (LC-MS/MS) for the determination of cannabidiol and its active metabolite 7-hydroxy-cannabidiol in microvolumes of serum and saliva (50 μL), to be used as a tool for therapeutic drug  monitoring (TDM) and pharmacokinetic studies. After on-line solid phase extraction cannabidiol, 7-hydroxy-cannabidiol and the internal standard cannabidiol-d3 are separated on a monolithic C18 column under gradient conditions. Calibration curves are linear within the validated concentration range (10-1000 ng/mL for cannabidiol and 5-500 ng/mL for 7-hydroxy-cannabidiol).

The method is accurate (intraday and interday accuracy within 94-112% for cannabidiol, 91-109% for 7-hydroxy-cannabidiol), precise (intraday and interday precision <11.6% for cannabidiol and <11.7% for 7- hydroxy-cannabidiol) and sensitive, with a LOQ of 2.5 ng/mL for cannabidiol and 5 ng/mL for 7-hydroxy-cannabidiol. The stability of the analytes was confirmed under different storage conditions. Extraction recoveries were in the range of 81-129% for cannabidiol and 100-113% for 7-hydroxy-cannabidiol.

The applicability of the method to TDM was demonstrated by analysis of human serum and saliva samples obtained from patients with epilepsy treated with cannabidiol.

本数据库收录了与论文《在线固相萃取-高效液相色谱-串联质谱法用于人血清及唾液中大麻二酚与7-羟基大麻二酚的治疗药物监测》相关的原始数据。

大麻二酚（Cannabidiol）是一种新型抗癫痫药物，已获欧盟与美国批准，用于治疗伦诺克斯-加斯托综合征（Lennox-Gastaut syndrome）、德拉韦综合征（Dravet syndrome）及结节性硬化症相关的癫痫发作。本文报道了一种简便新颖的液相色谱-串联质谱（LC-MS/MS）方法，可在微量血清及唾液样本（50 μL）中定量检测大麻二酚及其活性代谢物7-羟基大麻二酚，适用于治疗药物监测（TDM）与药代动力学研究。该方法先通过在线固相萃取，随后在C18整体柱上以梯度洗脱条件分离大麻二酚、7-羟基大麻二酚及内标大麻二酚-d3。校准曲线在验证浓度范围内呈良好线性关系（大麻二酚为10~1000 ng/mL，7-羟基大麻二酚为5~500 ng/mL）。

本方法准确度优异（大麻二酚的日内、日间准确度为94%~112%，7-羟基大麻二酚为91%~109%），精密度良好（大麻二酚的日内、日间精密度均<11.6%，7-羟基大麻二酚均<11.7%），且灵敏度较高，大麻二酚的定量下限（LOQ, Limit of Quantitation）为2.5 ng/mL，7-羟基大麻二酚为5 ng/mL。研究证实了分析物在不同储存条件下的稳定性，大麻二酚的萃取回收率为81%~129%，7-羟基大麻二酚为100%~113%。

通过对接受大麻二酚治疗的癫痫患者的人血清及唾液样本进行分析，验证了本方法在治疗药物监测中的适用性。