Development of an UHPLC-MS/MS method to determine cutaneous biodistribution of cannabidiol after topical application of cannabidiol gel assisted by iontophoresis

Cannabidiol has potential for use in skin disease therapy, so it is important to know the cutaneous biodistribution of cannabidiol after topical application of cannabidiol formulations. However, currently existing quantification methods for the investigation of cannabidiol skin distribution are not optimal. This study aimed to establish a method for the determination of cannabidiol in skin samples by UHPLC-MS/MS. A BEH C18 (50.0 x 2.1 mm, 2.5 mu m) column was used; the mobile phase consisted of acetonitrile-0.1% formic acid (70:30, v/v), the flow rate was 0.2 mu l center dot min(-1) and the column temperature was 30 degrees C. Positive-ion mode with multiple reaction monitoring detection was used to quantify cannabidiol (m/z 315.1 -> 193.1) while diphenhydramine (m/z 256.3 -> 167.08) served as the internal standard. Good linearity was shown in the range of 1-200 ng center dot ml(-1) for cannabidiol with correlation coefficients of >0.999. The LLOQ was 1 ng center dot ml(-1). The intra-day and inter-day RSDs of cannabidiol were all <2%. A cryo-sectioning technique combined with the UHPLC-MS/MS method was used to successfully determine cannabidiol levels in a series of very thin skin layers.