Usefulness of Saliva for Measurement of 3,4-Methylenedioxymethamphetamine and Its Metabolites: Correlation with Plasma Drug Concentrations and Effect of Salivary pH

After a single 100-mg dose of MDMA, concentrations in saliva ranged from 1728.9 to 6510.6 μg/L, peaking at 1.5 hours, then declining to a mean of 126.2 μg/L at 24 hours. The saliva-to-plasma ratio varied from 32.3 to 1.2, with a peak of 18.1 at 1.5 hours. Salivary pH decreased by 0.6 units after drug administration, from a predose mean of 7.4 to 6.9 at 1.5 hours and 6.8 at 4 hours. Measuring MDMA in saliva offers a noninvasive alternative to plasma testing for clinical and toxicologic studies.

Study at a glance

Abstract

Abstract Background: Saliva is an alternative biologic matrix for drugs-of-abuse testing that offers the advantages of noninvasive, rapid, and easy sampling. We studied the excretion profile of 3,4-methylenedioxymethamphetamine (MDMA) and its metabolites in both saliva and plasma, as well the effect of the drug on salivary pH. Methods: Saliva and plasma samples were obtained from eight healthy MDMA consumers after ingestion of a single 100-mg dose of the drug. Concentrations of MDMA and its main metabolites, 3,4-methylenedioxyamphetamine (MDA) and 4-hydroxy-3-methoxymethamphetamine (HMMA), in saliva and plasma were measured by gas chromatography-mass spectrometry. Apparent pharmacokinetic parameters for MDMA in saliva were estimated, and the saliva-to-plasma ratio at each time interval was calculated and correlated with salivary pH. Results: MDMA, MDA, and HMMA were detected in saliva. Salivary concentrations of MDMA were 1728.9–6510.6 μg/L and peaked at 1.5 h after drug intake. This was followed by a progressive decrease, with a mean concentration of 126.2 μg/L at 24 h. The saliva-to-plasma ratio was 32.3–1.2, with a peak of 18.1 at 1.5 h after drug administration. Salivary pH seemed to be affected by MDMA administration; pH values decreased by 0.6 units (mean pH values of 6.9 and 6.8 at 1.5 and 4 h after drug administration vs predose pH of 7.4). Conclusions: Measurement of MDMA in saliva is a valuable alternative to determination of plasma drug concentrations in both clinical and toxicologic studies. On-site testing is also facilitated by noninvasive and rapid collection of salivary specimens.