Abstract
A gas chromatography-mass spectrometric (GC/MS) procedure for the determination of amineptine (dihydro-10, 11-dibenzo[a, d] cycloheptenyl-5-amino-7-heptanoic acid) and its main metabolites in human urine was described. Amineptine has been known to be extensively metabolized by the ${\beta}$-oxidation of the heptanoic side chain with formation of pentanoic side chain metabolite ($C_5$-metabolite), and lactamizarion by internal dehydration of (${\beta}$-oxidized metabolite (${\delta}$-lactam). The detection of these compounds was based on acid hydrolysis, liquid-liquid extraction and trimethylsilylated derivatization of the carboxylic acid group. For the determination of amineptine and its metabolites in biological fluids, selected ions at the m/ 192, molecular ion and one of the characteristic ions were monitored by GC/MS. On the excretion study of amineptine in human urine, 70-90% of amineptine, ${\delta}$-lactam, and $C_5$-metabolite were found to be excreted within 4 hours and their excretion completed within 20 hours.
뇨시료 중 amineptine의 (dihydro-10, 11-dibenzo[a, d] cycloheptenyl-5-amino-7-heptanoic acid) metabolites를 분석하기 위한 최적조건을 찾기 위하여 pH 변화에 따른 추출률과 세가지의 유도체화시약에 대한 반응성을 조사해본 결과 pH는 9.5, 유도체화시약은 carboxylic acid group에 MSTFA로 반응 시켰을 경우 좋은 결과를 나타내었다. GC/MS를 이용하여 amineptine을 복용한 사람의 뇨를 분석한 결과 amineptine과 그 대사물질인 dihydro-10, 11-dibenzo[a, d] cycloheptenyl-5-amino-5-pentanoic acid ($C_5$-metabolite)와 $C_5$-metabolite의 lactamized product인 ${\delta}$-lactam을 확인하였다. Amineptine과 그 metabolite들을 GC/MS-SIM mode로 분석하기 위한 monitoring ion들은 m/z 192를 공통 이온으로 선정하였으며, 각각의 분자이온을 선정하였다. Amineptine의 excretion study 결과, amineptine, ${\delta}$-lactam 및 $C_5$-metabolite는 4시간이내에 70-90%가 배설되었고 20시간 이내에 거의 배설이 완결되었다.
