Mass Spectrometric Interrogation of Earwax: Toward the Detection of Ménière's Disease.

Abstract

Many diseases remain difficult to identify because the occurrence of characteristic biomarkers within traditional matrices such as blood and urine remain unknown. Disease diagnosis could, therefore, benefit from the analysis of readily accessible, non-traditional matrices that have a high chemical content and contain distinguishing biomarkers. One such matrix is cerumen (i.e., earwax), whose chemical complexity can pose challenges when analyzed by conventional methods. A combination of cerumen chemical profiles analyzed by gas chromatography-mass spectrometry (GC-MS) and direct analysis in real time-high-resolution mass spectrometry (DART-HRMS) were investigated to ascertain the possible presence of the rare otolaryngological disorder Ménière's disease. This illness is currently identified via "diagnosis by exclusion" in which the disease is distinguished from others with overlapping symptoms by the process of elimination. GC-MS revealed a chemical profile difference between those with and without a Ménière's disease diagnosis by a visually apparent diminution of the compounds present in the Ménière's disease samples. DART-HRMS revealed that the two classes could be differentiated using three fatty acids: cis-9-hexadecenoic acid, cis-10-heptadecenoic acid, and cis-9-octadecenoic acid. These compounds were subsequently quantified by GC-MS and overall, the amounts of these fatty acids were decreased in Ménière's disease patients. The average levels for non-Ménière's disease samples were 7.89 μg/mg for cis-9-hexadecenoic acid, 0.87 μg/mg for cis-10-heptadecenoic acid, and 4.94 μg/mg for cis-9-octadecenoic acid. The average levels for Ménière's disease samples were 1.70 μg/mg for cis-9-hexadecenoic acid, 0.13 μg/mg for cis-10-heptadecenoic acid, and 2.07 μg/mg for cis-9-octadecenoic acid. The confidence levels for cis-9-hexadecenoic acid, cis-10-heptadecenoic acid, and cis-9-octadecenoic acid were 98.7%, 99.9%, and 95.4%, respectively. The results suggest that assessment of the concentrations of these fatty acids could be a useful clinical tool for the more rapid and accurate detection of Ménière's disease.