Introduction Winlevi® (clascoterone) topical cream, 1% is newly approved for the treatment of acne vulgaris. Clascoterone (CLA) is not stable in physiological solutions and can be easily hydrolyzed to cortexolone (COR) via cortexolone 21-propionate (COR-21) at body temperature, posing an analytical challenge. This study aims to develop an analytical method for in vitro skin permeation test (IVPT) of Winlevi®. Methods Simultaneous quantitation of CLA, COR, and qualification of COR-21 in IVPT samples was performed using a Sciex Exion UHPLC system coupled to a Qtrap 6500+ tandem mass spectrometer equipped with a Turbo Ion Spray source (UHPLC-MS/MS, Sciex, Framingham, MA). Analytes and internal standard were separated on a C18 UPLC column. The mobile phase consisting of 0.1% formic acid in water and 0.1% formic acid in acetonitrile/methanol was delivered at 0.8 mL/min with a 2-min gradient. The mass spectrometer was operated in the positive mode with multiple reaction monitoring. Nitrogen was used as the nebulizer, heater and curtain gas, and the collision gas. Analyst® Software was used for data acquisition and processing. IVPT was carried out using in-line flow-through cells (PermeGear, Inc., Hellertown, PA). The receptor solution was PBS containing 5% (w/v) of bovine serum albumin (BSA) as solubilizer. A finite dose of cream was applied to the skin maintained at 32.0○C. IVPT samples were collected and processed to remove BSA before analysis. Results and Discussion Calibration curves of CLA and COR were linear over the validated range of 0.5-1000 ng/mL. Correlation coefficient was &gt; 0.99. The analytical method was determined to be accurate and precise at all quality control levels. All analytes were observed as early as 2 h in the receptor solution, indicating metabolism of CLA during IVPT. In addition, timely sample processing as the test progresses could prevent post-IVPT metabolism and loss of CLA in the permeation samples. Conclusion An UHPLC-MS/MS method was successfully developed for quantifying the skin permeation of CLA and COR from Winlevi®. The data enhances our understanding of permeation of CLA and its metabolites following topical application of the cream.

Method development for the evaluation of in vitro skin permeation of clascoterone from clascoterone topical cream, 1%

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