Study of human urinary metabolism of fenfluramine using gas chromatography-mass spectrometry.
The metabolism of (+/-)fenfluramine, 1-(m-trifluoromethylphenyl)-2-N-ethylpropane, an anoretic agent, was investigated in humans. The analysis method was based on the use of ion-exchange resin extraction, solid-phase purification on the Bond Elut1M C8 cartridge, gradient elution high-performance liquid chromatography, enzymic hydrolysis of conjugates, further purification by Bond Elut C8 cartridge, derivatisation and capillary column gas chromatography-mass spectrometry (GC-MS). After administration of a 1 mg kg-1 oral dose, four metabolites plus unchanged fenfluramine were recovered in the 0-24 h urine from human volunteers and characterised by GC-MS. In the conjugated form, fenfluramine, norfenfluramine and m-trifluoromethylhippuric acid were detected by GC-MS. In the aglycone form, the major metabolite, 1-(m-trifluoromethylphenyl)-1,2-propane diol (fenfluramine diol), was monitored using GC-MS. The mass spectral characteristics of the m-trifluoromethylhippuric acid methyl ester, 1-(m-trifluoromethylphenyl)-1,2-propane ditrifluoracetate derivatives and the norfenfluramine and fenfluramine free base obtained under electron-impact ionization are presented. The metabolism of fenfluramine is discussed including a metabolic pathway in man accounting for the formation of its biotransformation products.
Brownsill
R
R
Servier Research and Development, Fulmer Hall, Slough, U.K.
Wallace
D
D
Taylor
A
A
Campbell
B
B
D001711:Biotransformation; D002855:Chromatography, Thin Layer; D005260:Female; D005277:Fenfluramine / Q000652:urine*; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D007202:Indicators and Reagents; D008297:Male
D007202:Indicators and Reagents; D005277:Fenfluramine