Plasma Menthol Glucuronide as a Biomarker of Acute Menthol Inhalation

Objectives: Menthol is often added to cigarettes and e-cigarette solutions for its cooling and anti-irritant effects, and may contribute to development of nicotine dependence, particularly in vulnerable populations such as adolescents, and among African Americans. Menthol is rapidly metabolized to menthol glucuronide (MG) with little or no unconjugated menthol measurable in venous blood. Human challenge studies of the effects of inhaled menthol, and of its interactions with nicotine, would benefit from a quantitative measure of acute menthol exposure. Our objective was to determine whether plasma MG concentrations might be a suitable quantitative biomarker of acute menthol exposure following its inhalation.

Methods: We performed a secondary analysis of plasma MG concentrations obtained during a study of the effects of inhaled menthol on behavioral responses to intravenous nicotine. MG concentrations were followed over time in venous plasma from 48 participants following inhalation of aerosols from e-cigarettes employing solutions containing either of 2 menthol concentrations or placebo.

Results: Whereas plasma MG concentrations were variable, they showed a dose-dependent increase following menthol inhalation.

Conclusions: Measurement of plasma MG may be useful to assess inter-individual differences in acute menthol exposure in human challenge studies involving menthol inhalation.