|SOFT - TIAFT 1998||Poster Session 3||Thursday October 8, 1998|
METHYLEPHEDRINE FINDINGS AFTER INTAKE OF METAMFEPRAMONE - STUDIES ON THE METABOLISM AND THE TOXICOLOGICAL DETECTION OF METAMFEPRAMONE USING GC-MS|
Thomas Kraemer, Negar Makkinejad, and Hans H. Maurer
Institute of Pharmacology and Toxicology, Department of Toxicology, University of Saarland, D-66421 Homburg (Saar), Germany
|Methylephedrine (ME), a sympathomimetic amine, is ingredient of many over-the-counter cold medications. ME abuse has been reported in some asian countries. Kunsman et al. reported ME findings in drug testing samples in the U.S.A. (1). In our lab, ME was found in urine of patients denying its intake. The only known medication was metamfepramone (R,S-2-dimethylaminopropiophenone, MP), a sympathomimetic used as antihypotonic or as cold medication. To study, whether and how long ME, methylpseudoephedrine, ephedrine (EP) and/or pseudoephedrine (PE) can be detected in urine after intake of MP, we reinvestigated the metabolism of MP, its detection within our STA procedure and the duration of detectability.
The metabolites were identified in urine after cleavage of conjugates, extraction and derivatization by acetylation using GC-MS. Besides the parent compound, the following metabolites could be identified in urine: ME, EP, PE, nor-EP, nor-MP, hydroxy-nor-MP and hydroxy-nor-EP. Differentiation of the ME and EP diastereomers was achieved after trifluoroacetylation. Three partly overlapping metabolic pathways could be postulated: 1) reduction of the ketogroup, 2) one- and two-fold N-demethylation and 3) ring hydroxylation.
After intake of 20 mg of MP, its main metabolite ME could be detected for about 140 h, EP and PE for about 132 h (n = 3). Nor-MP, the MP specific metabolite could only be detected for about 52 h. Therefore, in the time window from 52 to 140 h differentiation of MP intake from ME, EP and/or PE use was not possible. The analytical recoveries were 55 % for MP, 98 % for ME and 75 % for PE and the LOD's were 50 ng/mL for MP and 10 ng/mL for ME, EP and PE.
1. G.W. Kunsman, R. Jones, B. Levine and M.L. Smith; Methylephedrine Concentrations in Blood and Urine Specimens, Abstracts to the SOFT annual meeting, October 5-9, 1997, Utah