3,4-Methylenedioxymethamphetamine quantification via benchtop 1H qNMR spectroscopy: Method validation and its application to ecstasy tablets collected at music festivals

Anca Frinculescu; Alexander F G Maier; Trevor Shine; John Ramsey; Juan F Araneda; Susanne D Riegel; Nunzianda Frascione; Vincenzo Abbate

doi:10.1016/j.jpba.2022.114728

3,4-Methylenedioxymethamphetamine quantification via benchtop ¹H qNMR spectroscopy: Method validation and its application to ecstasy tablets collected at music festivals

J Pharm Biomed Anal. 2022 May 30:214:114728. doi: 10.1016/j.jpba.2022.114728. Epub 2022 Mar 16.

Authors

Anca Frinculescu¹, Alexander F G Maier², Trevor Shine³, John Ramsey³, Juan F Araneda², Susanne D Riegel², Nunzianda Frascione⁴, Vincenzo Abbate⁵

Affiliations

¹ Department of Analytical, Environmental and Forensic Sciences, King's College London, 150 Stamford Street, London SE1 9NH, United Kingdom; TICTAC Communications Ltd., Room 1.159 Jenner Wing, St. George's University of London, Cranmer Terrace, London SW17 0RE, United Kingdom.
² Nanalysis Corp., 1, 4600 5 Street NE, Calgary, AB T2E 7C3, Canada.
³ TICTAC Communications Ltd., Room 1.159 Jenner Wing, St. George's University of London, Cranmer Terrace, London SW17 0RE, United Kingdom.
⁴ Department of Analytical, Environmental and Forensic Sciences, King's College London, 150 Stamford Street, London SE1 9NH, United Kingdom.
⁵ Department of Analytical, Environmental and Forensic Sciences, King's College London, 150 Stamford Street, London SE1 9NH, United Kingdom. Electronic address: vincenzo.abbate@kcl.ac.uk.

PMID: 35349940
DOI: 10.1016/j.jpba.2022.114728

Abstract

We describe a method validation for the quantification of 3,4-methylenedioxymethamphetamine (MDMA) in tablets based on the United Nations Office on Drugs and Crime (UNODC) guideline for quantitative Nuclear Magnetic Resonance analysis (qNMR). qNMR experiments were carried out on a 60 MHz benchtop NMR spectrometer employing ethylene carbonate as an internal calibrant. A series of 'ecstasy' tablets seized at music events were quantified and the results discussed regarding their within-batch variation and yearly median dose. The method showed good specificity and selectivity, with linearity, precision, accuracy, and recovery well within the UNODC recommended criteria. The limit of detection and quantification are 0.33 mg/mL and 0.10 mg/mL respectively, proving the method works well on small amounts of MDMA. Overall, the lowest amount of MDMA free base detected in this study was 9.35 mg in a piperazine mix, while the highest dosed tablet contained 237.55 mg MDMA free base, with a 9.1% decrease in median amount compared to the pre-pandemic data (2019), but still higher than the data collected in a previous study (105 mg median amount of MDMA free base in 2018). The within-batch variation was insignificant for one of the seizures but showed greater variation for the other, which confirmed that the MDMA content of a single tablet may not reflect that of the whole batch. This dynamic upward change in tablet dosage highlights the importance of ongoing trend monitoring and specific prevention intervention to counteract the negative consequences associated with MDMA use. Benchtop NMR has been successfully employed in quality control, material science and more recently, drug analysis. The present study demonstrates its beneficial application in forensic science overcoming the limitations of currently available instruments and techniques employed in harm reduction and field testing.

Keywords: Benchtop NMR; Illicit drug analysis; MDMA; Method validation; Quantitative analysis; qNMR.

MeSH terms

Hallucinogens* / analysis
Holidays
Illicit Drugs* / analysis
Magnetic Resonance Spectroscopy
Music*
N-Methyl-3,4-methylenedioxyamphetamine* / analysis
N-Methyl-3,4-methylenedioxyamphetamine* / chemistry
Tablets / chemistry

Substances

Hallucinogens
Illicit Drugs
Tablets
N-Methyl-3,4-methylenedioxyamphetamine