HPLC/TOF-MS联用鉴定尼麦角林比格犬体内代谢物研究
Metabolites identification of nicergoline in beagle dog blood by the study of CID fragmentation pathways using HPLC/TOF-MS
刘炜 1王建华2
作者信息
- 1. 北京世纪坛医院药剂科,北京,100038
- 2. 解放军总医院老年医学研究所,北京,100853
- 折叠
摘要
目的:尼麦角林是麦角菌中主要活性成分麦角碱的衍生物,在体内的实验中表现了显著的阻断α受体和扩张血管的活性.本文首次采用高效液相色谱串联飞行时间质谱法,对尼麦角林比格犬体内的主要代谢产物进行了研究.方法:高效液相色谱串联飞行时间质谱法,安捷伦TC-C18反相色谱柱(150 mm ×4.6 mm,5μm,USA).流动相为二元系统梯度洗脱:A:水,含1 mL/L甲酸;B:乙腈,含1 mL/L甲酸.结果:共鉴定了3个代谢产物,其中10α-甲氧基.6-二甲基-8β-羟甲基尼麦角林(MDL)是丰要的代谢产物.同时详细地研究了尼麦角林及其代谢产物的多级质谱裂解决规律,提出了菲杂环的逐级裂解规律.结论:方法准确,可为血药浓度监测提供精密的分析方法.
Abstract
AIM:Nicergoline(NIC)is a semi-synthesized derivate of ergotine from Ciavieps purpurca,which shows the significant bio-effects of blocking the α-receptor and expanding blood vessels in vivo.In the present study,the major metabolites of NIC in beagle dog blood were studied for the first time after an oral administration of 30 mg NIC using liquid chromatography-time of flight ulass spectrometry(HPLC/TOF-MS). METHODS:HPLC/TOF-MS,Agilent TC-C18,The mobile phase Was a gradient of a mixture of A(H_2O,with 1 mL/L formic acid inside)and B(CNCH_3,with 1 mL/L formic acid inside).RESULTS:Three metabolites were detected and identified with 6-dimethy-8 β-hydroxymethy-10α-methoxy nicergoline(MDL)as the major metabolite.The MSn behaviors of NIC and all its identified metabolites were studied in detail,which showed that they all have some common fragmentation patterns as a result of gradient cleavage of phenanthrene heterocyclic ring.CONCLUSION:The method is accurate and sensitive,and can be used for blood concentration monitoring.
关键词
尼麦角林/代谢研究/液相色谱-飞行时间质谱Key words
nicergoline/metabolites identification/HPLC/TOF-MS引用本文复制引用
出版年
2009
NETL
NSTL
维普
万方数据