Sensitive and selective gas chromatographic methods for the quantitation of camphor, menthol and methyl salicylate from human plasma.

Analytical methods using gas chromatography-flame ionization detection (GC-FID) for the quantitation of camphor and menthol and GC-MS for the quantitation of methyl salicylate have been developed for measurement of low concentrations from human plasma. Anethole serves as the internal standard for camphor and menthol and ethyl salicylate serves as the internal standard for methyl salicylate. Plasma samples undergo multiple, sequential extractions with hexane in order to provide optimal recovery. For menthol and camphor, the extracting solvent is reduced in volume and directly injected onto a capillary column (Simplicity-WAX). Extracted methyl salicylate is derivatized with BSTFA prior to injection onto a capillary column (Simplicity-5). Between-day variation (% RSD) at 5 ng/ml varies from 6.2% for methyl salicylate to 13.5% for camphor. The limit of detection for each analyte is 1 ng/ml and the limit of quantitation is 5 ng/ml. These analytical methods have been used in a clinical study to assess exposure from dermally applied patches containing the three compounds.