中毒患者生物检材中卡马西平及其代谢物的气相色谱质谱分析  

Determination of carbamazepine and its metabolites in biological samples from a poisoned patient by GC-MS analysis

作　　者：周丽屏[1] 陈纠[1] 郭嘉明[1] 刘移民[1] 

机构地区：[1]广州市职业病防治院职业卫生评价检测中心,广东广州510620

出　　处：《中国药理学与毒理学杂志》2016年第9期961-966,共6页Chinese Journal of Pharmacology and Toxicology

基　　金：广州市职业环境与健康效应实验室建设项目(2014SY000020)~~

摘　　要：目的探讨卡马西平(CBZ)在中毒患者不同生物检材中的主要代谢产物及其代谢途径。方法通过收集广州市职业病防治院1例CBZ中毒患者服用CBZ约6 h后的胃液、血液及尿液,以未服用CBZ的正常人体液作为对照,采用气相色谱质谱法进行分析,用NIST98谱库检索系统对所得质谱图进行图库检索,并根据质谱裂解规律及相关文献报道进行图谱解析,鉴定CBZ代谢物结构,推断其代谢途径。结果在CBZ中毒患者胃液中检出亚氨基茋(M1)1种代谢产物,血液中检出M1、9-甲基吖啶(M2)、9-丙基-9,10-二氢化吖啶(M4)及未知代谢产物M3共4种代谢产物,尿液中检出M1、M2、M4、吖啶(M5)、吖啶酮(M6)、9,10-二氢吖啶(M7)、10,11-环氧卡马西平(M8)、9-吖啶甲醇(M9)、10,11-二羟卡马西平(M10)、2-甲基-吖啶酮(M12)、4-甲基-吖啶酮(M13)及未知代谢产物M3和M11共13种代谢产物。M3和M11代谢产物结构仍需进一步分离及鉴定。在胃液、血液和尿液中,CBZ的代谢物形式存在较大差异,且仅极少量以原药形式在尿液中排出。结论经过气相色谱质谱分析和图库检索,筛查鉴定出中毒患者体内CBZ的13种代谢产物,并推断其代谢途径。OBJECTIVE To investigate the forms of carbamazepine and its metabolites in the gastric juice,blood and urine samples from a poisoned patient and its metabolic pathways. METHODS The gastric juice,blood and urine samples were obtained from a patient who was rushed to the Hospital of Prevention and Treatment for Occupational Diseases to be treated for an overdose of carbamazepine for about six hours. The samples were analyzed by gas chromatography-mass spectrometry. The metabolites were identified from their mass spectra by comparison with spectra in NIST 98 libraries.The metabolic pathways were inferred by fragmentation regularities of mass spectra and the published data. RESULTS The results showed that only M1 was found in the gastric juice sample. Four metabolites,such as iminostilbene（M1）,9-methyl-acridine（M2）,9-propyl-acridan（M4）and M3,were found in the blood sample and thirteen metabolites,including M1,M2,M4,acridine（M5）,acridone（M6）,9,10- dihydro Acridine（M7）, 1a,10b- dihydro- 6H- dibenz[b,f]oxireno[d]azepine- 6- carboxamide（M8）,9- acridinemethanol（M9）,10,11- dihydrodiol- carbamazepine（M10）,2- methyl- acridone（M12）,4-methyl-acridone（M13）,undetermined M3 and M11,were found in the urine from the poisoned patient. The forms of carbamazepine metabolites in the gastric juice,blood and urine were different.Little carbamazepine was found in the urine after metabolism. CONCLUSION Based on the analysis by gas chromatography- mass spectrometry and identification of NIST 98 libraries,the metabolites could be identified accurately,which can help analyze the metabolic mechanism and pathways of carbamazepine.

关 键 词：气相色谱质谱法 卡马西平 代谢物 

分 类 号：R595[医药卫生—内科学]