Composition profiling of seized ecstasy tablets by Raman spectroscopy

Abstract

Raman spectroscopy with far-red excitation has been investigated as a simple and rapid technique for composition profiling of seized ecstasy (MDMA, N-methyl-3,4-methylenedioxyamphetamine) tablets. The spectra obtained are rich in vibrational bands and allow the active drug and excipient used to bulk the tablets to be identified. Relative band heights can be used to determine drug/excipient ratios and the degree of hydration of the drug while the fact that 50 tablets per hour can be analysed allows large numbers of spectra to be recorded. The ability of Raman spectroscopy to distinguish between ecstasy tablets on the basis of their chemical composition is illustrated here by a sample set of 400 tablets taken from a large seizure of > 50,000 tablets that were found in eight large bags. The tablets are all similar in appearance and carry the same logo. Conventional analysis by GC-MS showed they contained MDMA. Initial Raman studies of samples from each of the eight bags showed that despite some tablet-to-tablet variation within each bag the contents could be classified on the basis of the excipients used. The tablets in five of the bags were sorbitol-based, two were cellulose-based and one bag contained tablets with a glucose excipient. More extensive analysis of 50 tablets from each of a representative series of sample bags have distribution profiles that showed the contents of each bag were approximately normally distributed about a mean value, rather than being mixtures of several discrete types. Two of the sorbitol-containing sample sets were indistinguishable while a third was similar but not identical to these, in that it contained the same excipient and MDMA with the same degree of hydration but had a slightly different MDMA/sorbitol ratio. The cellulose-based samples were badly manufactured and showed considerable tablet-to-tablet variation in their drug/excipient ratio while the glucose-based tablets had a tight distribution in their drug/excipient ratios. The degree of hydration in the MDMA feedstocks used to manufacture the cellulose-, glucose- and sorbitol-based tablets were all different from each other. This study, because it centres on a single seizure of physically similar tablets with the same active drug, highlights the fact that simple physical descriptions coupled with active drug content do not in themselves fully characterize the nature of the seized materials. There is considerable variation in the composition of the tablets within this single seizure and the fact that this variation can be detected from Raman spectra demonstrates that the potential benefits of obtaining highly detailed spectra can indeed translate into information that is not readily available from other methods but would be useful for tracing of drug distribution networks.

Recent applications of Chemical Imaging to pharmaceutical process monitoring and quality control

“…It was demonstrated that the eigenvalue-based criteria for choosing principal components was ineffective for these Raman Chemical Images, and the author remarked that the basic postulates of PCA could pose a significant problem when applied to Raman mapping spectra. For NIR mapping spectra, interpretation of PCA proved difficult; problems were associated with associating pure component spectra Bell et al [51] , [55], [56] and [57] published findings on the development of quantitative analytical methods for Raman analysis of solid dosage forms. In one paper, this research team reported results on Raman mapping of seized ecstasy tablets [51].…”

Electrochemical and spectroscopic characterisation of amphetamine-like drugs: Application to the screening of 3,4-methylenedioxymethamphetamine (MDMA) and its synthetic precursors

“…Although there are some reported studies on the Raman analysis of amphetamine-like compounds [14][15][16][17][18][19][20][21], these experiments have only focused on particular regions of the vibrational spectra.…”

Development of sampling methods for Raman analysis of solid dosage forms of therapeutic and illicit drugs

“…It was assumed, rather than explicitly demonstrated, that the large surface area from which the signal was collected ensured that this spectrum was representative of the average composition of the sample. 1,3 Although this rotating tablet arrangement is widely used, it is typically only applied in situations where manually loading tablets one at a time is acceptable because it is difficult to combine sample rotation with automated high-throughput analysis of large numbers of tablets. In the work here, the approach taken was to mount sets of tablets on a motorized sample stage and to record data from a grid of points on each tablet (and from each tablet in the sample holder) by stepping the stage in the x and y directions.…”