Variability in content and dissolution profiles of MDMA tablets collected in the UK between 2001 and 2018 – A potential risk to users?

MDMA (Ecstasy) tablets collected in the UK between 2001 and 2018 show increasing MDMA content over time, with median free-base content exceeding 100 mg for the first time in 2018. Analysis of 412 tablets revealed dramatic within-batch content variability, with differences up to 136 mg. Dissolution testing on 247 tablets showed that tablets can be categorized as fast-, intermediate-, or slow-releasing, but no tablet characteristics predicted dissolution classification, meaning users cannot know a tablet's release profile beforehand. Within-batch variation in dissolution rate was also observed. Rapid assessment of MDMA content alone does not account for variability in remaining tablets in a batch or dissolution profiles. High-content, slow-releasing tablets may cause delayed or prolonged toxicity, increasing risk of re-dosing if absorption is delayed.

Study at a glance

Abstract

Abstract 3,4‐Methylenedioxymethamphetamine (MDMA, Ecstasy) tablets are widely used recreationally, and not only vary in appearance, but also in MDMA content. Recently, the prevalence of high‐content tablets is of concern to public health authorities. To compare UK data with other countries, we evaluated MDMA content of 412 tablets collected from the UK, 2001–2018, and investigated within‐batch content variability for a sub‐set of these samples. In addition, we investigated dissolution profiles of tablets using pharmaceutical industry‐standard dissolution experiments on 247 tablets. All analyses were carried out using liquid chromatography−tandem mass spectrometry (LC–MS/MS). Our data supported other studies, in that recent samples (2016–2018) tend to have higher MDMA content compared to earlier years. In 2018, the median MDMA content exceeded 100 mg free‐base for the first time. Dramatic within‐batch content variability (up to 136 mg difference) was also demonstrated. Statistical evaluation of dissolution profiles at 15‐minutes allowed tablets to be categorized as fast‐, intermediate‐, or slow‐releasing, but no tablet characteristics correlated with dissolution classification. Hence, there would be no way of users knowing a priori whether a tablet is more likely to be fast or slow‐releasing. Further, within‐batch variation in dissolution rate was observed. Rapid assessment of MDMA content alone provides important data for harm reduction, but does not account for variability in (a) the remainder of tablets in a batch, or (b) MDMA dissolution profiles. Clinical manifestations of MDMA toxicity, especially for high‐content, slow‐releasing tablets, may be delayed or prolonged, and there is a significant risk of users re‐dosing if absorption is delayed.