Organic impurity profiling of 3,4-methylenedioxyamphetamine (MDA) synthesised from helional.

The organic impurity profile of 3,4-methylenedioxyamphetamine (MDA) synthesised from helional via the "twodogs" method was examined to identify route-specific and condition-specific impurities. The synthesis used a condensation reaction, followed by a Beckmann rearrangement, then Hofmann rearrangement, and then conversion to a hydrochloride salt. Two chlorinating agents were investigated for the Hofmann rearrangement reaction, trichloroisocyanuric acid (TCCA) and sodium hypochlorite. Three route-specific impurities were identified in MDA using TCCA, and two of these impurities were condition-specific such that the impurities that formed were dependent on the alcohol used as solvent. Three additional impurities were identified as non-route-specific as they have previously been identified in MDA synthesised from 3,4-methylenedioxycinnamic acid or piperonal. These non-route-specific impurities were also identified in MDA synthesised using sodium hypochlorite. No impurities were detected in MDA hydrochloride. This study identified route- and condition-specific organic impurities in MDA synthesised via the "twodogs" synthetic route using helional as starting material. The results in this study provide further understanding into the illicit synthesis of MDA and highlight the expanding nature of precursors used for illicit drug manufacture. It provides valuable information to decision makers to enact legislative measures and restrict precursors of concern.

Disulfiram-like Reaction With Metronidazole: An Unsuspected Culprit.

The association of disulfiram-like reaction with concomitant use of metronidazole and alcohol has been reported in the literature; however, alcohol containing oral liquids may not always be identified as a culprit. A case of a 14-year-old patient who experienced a possible disulfiram-like interaction while receiving metronidazole and Prednisone Intensol solution is reported. Metronidazole oral suspension was initiated for treatment of Clostridium difficile-associated diarrhea. Later, a 5-day course of oral Prednisone Intensol solution was initiated. On day 2 of concomitant metronidazole and steroid therapy, the patient experienced severe discomfort and abdominal distention accompanied by new onset tachycardia. A disulfiram-like reaction between the steroid solution and metronidazole was suspected; therefore, the Prednisone Intensol was discontinued. The patient's mother reported that, following discontinuation, the patient slept well for the first time in 2 days. Use of the Naranjo Adverse Drug Reaction Probability Scale indicated a possible relationship (score of 4) between the concomitant medication use and the gastrointestinal discomfort and tachycardia. If this interaction between metronidazole and alcohol containing medications occurs, it may be initially unrecognized, potentially resulting in patient discomfort or harm. It is important for healthcare professionals to identify these potential drug-drug interactions so that alternative medications may be utilized and offending agents can be avoided or replaced.