Brownsill R, Wallace D, Taylor A, Campbell B
Servier Research and Development, Fulmer Hall, Slough, U.K.
J Chromatogr. 1991 Jan 2;562(1-2):267-77. doi: 10.1016/0378-4347(91)80584-y.
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.
对食欲抑制剂（±）芬氟拉明（1 - （间三氟甲基苯基） - 2 - N - 乙基丙烷）在人体中的代谢情况进行了研究。分析方法基于离子交换树脂萃取、Bond Elut1M C8柱上的固相净化、梯度洗脱高效液相色谱、结合物的酶促水解、Bond Elut C8柱进一步净化、衍生化以及毛细管柱气相色谱 - 质谱联用（GC - MS）。给人类志愿者口服1 mg/kg的剂量后，在0 - 24小时尿液中回收了四种代谢物以及未变化的芬氟拉明，并通过GC - MS进行了表征。在结合形式下，通过GC - MS检测到了芬氟拉明、去甲芬氟拉明和间三氟甲基马尿酸。在苷元形式下，使用GC - MS监测到主要代谢物1 - （间三氟甲基苯基） - 1,2 - 丙二醇（芬氟拉明二醇）。给出了在电子轰击电离下得到的间三氟甲基马尿酸甲酯、1 - （间三氟甲基苯基） - 1,2 - 丙烷二（三氟乙酸酯）衍生物以及去甲芬氟拉明和芬氟拉明游离碱的质谱特征。讨论了芬氟拉明的代谢情况，包括人体中其生物转化产物形成的代谢途径。
