Analysis of docosanol using GC/MS: Method development, validation, and application to ex vivo human skin permeation studies

Docosanol is the only US Food and Drug Administration (FDA) approved over-the-counter topical product for treating recurrent oral-facial herpes simplex labialis. Validated analytical methods for docosanol are required to demonstrate the bioequivalence of docosanol topical products. A gas chromatography/ selected ion monitoring mode mass spectrometry (GC/SIM-MS) method was developed and validated for docosanol determination in biological samples. Docosanol and isopropyl palmitate (internal standard) were separated on a high-polarity GC capillary column with (88% cyanopropy)aryl-polysiloxane employed as the stationary phase. The ions of m/z 83 and 256 were selected to monitor docosanol and isopropyl palmitate, respectively; the total run time was 20 min. The GC/SIM-MS method was validated in accordance with US FDA guidelines, and the results met the US FDA acceptance criteria. The docosanol calibration standards were linear in the 100-10000 ng/mL concentration range (R2 > 0.994). The recoveries for docosanol from the receptor fluid and skin homogenates were > 93.2% and > 95.8%, respectively. The validated method was successfully applied to analyze ex vivo human cadaver skin permeation samples. On applying Abreva (R) cream tube and Abreva (R) cream pump, the amount of docosanol that penetrated human cadaver skin at 48 h was 21.5 +/- 7.01 and 24.0 +/- 6.95 ng/mg, respectively. Accordingly, we concluded that the validated GC/SIM-MS was sensitive, specific, and suitable for quantifying docosanol as a quality control tool. This method can be used for routine analysis as a costeffective alternative to other techniques. (C)& nbsp;2021 The Authors. Published by Elsevier B.V. on behalf of Xi'an Jiaotong University.& nbsp;

Automated summary

A validated GC/SIM-MS method for quantifying docosanol in biological samples was developed and confirmed to be sensitive, specific, and suitable for quality control analysis of docosanol.