Designer drugs 2,5-dimethoxy-4-bromo-amphetamine (DOB) and 2,5-dimethoxy-4-bromo-methamphetamine (MDOB): studies on their metabolism and toxicological detection in rat urine using gas chromatographic/mass spectrometric techniques

Studies are described on the metabolism and the toxicological analysis of the amphetamine-derived designer drug 2,5-dimethoxy-4-bromo-amphetamine (DOB) and its corresponding N-methyl analogue 2,5-dimethoxy-4-bromo-methamphetamine (MDOB) in rat urine using gas chromatographic/mass spectrometric techniques. The identified metabolites indicated that DOB was metabolized by O-demethylation followed by oxidative deamination to the corresponding ketone as well as deamination followed by reduction to the corresponding alcohol. Other metabolic pathways were O,O-bisdemethylation or hydroxylation of the side chain followed by O-demethylation and deamination to the corresponding alcohol. The expected oxo compound after deamination could not be detected. All metabolites carrying hydroxy groups were found to be partly excreted in the conjugated form. MDOB underwent O-demethylation, O,O-bisdemethylation, or hydroxylation of the side chain followed by O-demethylation. Additional N-demethylation to DOB occurred, including the above-mentioned metabolites. Again, all metabolites carrying hydroxy groups were found to be partly excreted in the conjugated form. The authors' systematic toxicological analysis (STA) procedure using full-scan GC/MS after acid hydrolysis, liquid-liquid extraction, and microwave-assisted acetylation allowed the detection of an intake of a dose of DOB and MDOB in rat urine that corresponds to a common drug user's dose. Assuming a similar metabolism, the described STA procedure in human urine should be suitable as proof of an intake of DOB and MDOB. Copyright (c) 2006 John Wiley & Sons, Ltd.