Development and Validation of a Liquid-Liquid Extraction and Gas Chromatography/Mass Spectrometry Methodology for Cannabidiol Analysis in Human Plasma

Stefania      P.S. Camargo; Regina      H.C. Queiroz; Wilson      R. Malfara; Jose      A. de Souza Crippa; Antonio      W. Zuardi; Jaime      E.C. Hallak; Bruno      S. De Martinis

Abstract

Cannabidiol (CBD) is a cannabinoid found in the Cannabis sativa plant and it is devoid of the typical cognitive and psychological effects of Delta 9-tetrahydrocannabinol (Delta 9-THC). However, studies with animals suggest that CBD presents anxiolytic properties. In the face of evidence of a cannabinoid system in humans, and the growing interest in the therapeutic use of CBD, the purpose of the present study is to develop and validate an analytical methodology for determination of CBD in human plasma. The methodology developed is based on liquid-liquid extraction and gas chromatography/mass spectrometry, and it is linear in the concentration range from 2.5 to 250 ng/mL of plasma, with the limit of detection of 1.0 ng/mL. The precision of inter and intra assays was respectively in the range from 7.5% to 8.2% and from 2.5% to 7.0%. Accuracy of the values of inter and intra assays varied respectively from 1.3% to 8.6% and from 1.2% to 4.4%. Extraction efficiency obtained was in the range of 54.6% to 75.3%. The validated methodology was demonstrated to be rapid, sensitive and suitable for application in clinical studies, as determined by monitoring patients in a controlled administration trial with CBD.

Keywords: Cannabidiol, Human plasma, Gas chromatography/mass spectrometry, Anxiety, Therapeutic drug monitoring, Validation, Chromatographic Analysis, Limit of Detection, Limit of Quantification, Stability, Specificity, Precision, Accuracy