Measurement of 3,4-MDMA and Related Amines in Diagnostic and Forensic Laboratories

Clinical Laboratory Science, Spring 2005 by Skrinska, Victor A, Gock, Susan B

The phenylalkylamine derivatives, 3,4-methylenedioxymethamphetamine (MDMA, ecstasy, XTC, Adam), 3,4-methylenedioxyethamphetamine (MDEA, MDE, Eve), and 3,4-methylenedioxyamphetamine (MDA), are psychostimulants with hallucinogenic properties. MDA is also a metabolite of both MDMA and MDEA. These drugs are ring-substituted amphetamine derivatives that produce hallucinogenic, entactogenic ('love drug'), and stimulating effects.1-3 MDMA was initially developed as an appetite suppressant, however, its use as a therapeutic drug has been very limited.4 Because of its effects as a hallucinogenic psychostimulant with relatively low toxicity, it has emerged over the last two decades as a common recreational psychostimulant or 'club drug' at 'raves'.5 MDMA, MDEA, and MDA are often referred to as 'rave' or 'designer' drugs. They are produced in clandestine laboratories and have an increasing presence on the illicit drug market worldwide. Significant adverse health effects have been reported that include: serotonin neurotoxicity, severe psychiatric disorders, renal failure, malignant hyperthermia, hepatitis, rhabdomyolysis, and disseminated intravascular coagulation.6,8 A number of fatal outcomes associated with severe MDMA intoxication have been reported.9-12

ABBREVIATIONS: Adam = 3,4-methylenedioxymethamphetamine; ecstasy = 3,4-methylenedioxymethamphetamine; Eve = 3,4-methylenedioxyethamphetamine; GC = capillary gas chromatography; GC/MS = gas chromatography/mass spectrometry; HPLC = high performance liquid chromatography; MDA = 3,4-methylenedioxyamphetamine; MDE = 3,4-methylenedioxyethamphetamine; MDEA = 3,4-methylenedioxyethamphetamine; MDMA = 3,4-methylenedioxymethamphetamine; XTC = 3,4-methylenedioxy-methamphetamine.

INDEX TERMS: drug testing; hallucinogenic drugs.

Clin Lab Sci 2005;18(2):119

The analysis of MDMA, MDEA, and MDA can be broken down into several categories. The first is the need to identify the presence of the drugs in tablets that are seized and suspected to contain illicit drugs. The second is the need to detect 'rave' drugs onsite with the intent to determine recent use of the drugs. The third category is the typical laboratory drug screen used to determine either recent or chronic exposure to the drugs. And finally, the fourth category is forensic analysis of postmortem specimens for the presence of the drugs. The specimens, methodology, and instrumentation vary with each of the categories. Table 1 summarizes the methods that have been developed and reported for these categories.

ANALYSISOFTABLETS

Tablets containing MDMA and other psychostimulants are prepared in clandestine laboratories worldwide. The tablets vary in size and typically have logos such as a pitbull, sparrow, butterfly, 'e', or 'X-files' imprinted on the tablets.13 The concentration of the active ingredients varies widely even among tablets from same origin.14 The excipients or inert ingredients found in tablets include glucose, sorbitol, and cellulose.15 Despite variation in concentration of the active ingredients, analysis of the tablets is helpful in identification of the clandestine laboratory that manufactured them. A number of analytical techniques have been applied to the characterization of the seized tablets. Raman spectroscopy of the active components and the excipients in tablets has been successfully used to identify tablets from the same source based on the state of hydration and the drug/excipient ratio.15'18 Another approach is analysis of impurities and byproducts of synthesis by gas chromatography/mass spectrometry (GC/MS), capillary gas chromatography (GC), or high performance liquid chromatography (HPLC).19'20 Isotopic analysis of the tablets for the ratios of deuterium, carbon 13, and nitrogen 15 in the active ingredients has been reported as a characteristic that is unique to the site of manufacture and may be a reliable method of fingerprinting the tablets.21,22 Capillary zone electrophoresis with ultraviolet detection is a rapid method suitable for routine analysis of MDMA content in tablets.23

ONSITE DETECTION OF PSYCHOSTIMULANTS

When individuals at the scene of a 'rave' party, accident, or crime are taken into custody, the need arises for a rapid onsite detection method for MDMA and related drugs. Some immunoassays that have been developed for detection of methamphetamine have high cross reactivity with MDMA and MDA, which make the assays potentially suitable for onsite screens where abuse of psychostimulants is suspected.24 Procedures have been reported for onsite analysis of saliva and sweat.24'27 The concentrations of MDMA and MDA in saliva have pharmacokinetic parameters that are similar to plasma, thus demonstrating that saliva is a useful and less invasive alternative to analysis of plasma.28 Studies have shown that individuals taking a single 100 mg dose of MDMA consistently have detectable levels of MDMA in both sweat and saliva after 1.5 hours. After six hours, most individuals remain positive; however, the number of false negatives begins to increase significantly to almost 20%.25 Drugwipe� has been successfully applied to onsite screens of both saliva wiped from the tongue and sweat collected from armpits.26,27 The drug may be quantified and cutoff limits established with a hand photometer, Drugread�.26