A tandem mass spectrometric study of bile acids: Interpretation of fragmentation pathways and differentiation of steroid isomers
A tandem mass spectrometric study of bile acids: Interpretation of fragmentation pathways and differentiation of steroid isomers
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胆汁酸的串联质谱研究：碎裂途径的解释和类固醇异构体的分化
DOI：
10.1016/j.steroids.2011.11.008
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发表时间：
2012-02-01
期刊：
影响因子：
2.7
通讯作者：
Guo, De-an
中科院分区：
文献类型：
--
作者：
Qiao, Xue;Ye, Min;Guo, De-an
胆汁酸是在C-17处具有戊酸取代基的类固醇。它们是胆固醇排泄的终末产物，在人和动物体内起着重要的生理作用。胆汁酸易于检测，但由于其多环结构和各种羟基化模式，难以通过质谱法进行鉴定。在这项研究中，裂解途径的18个游离和结合胆汁酸的解释，通过使用串联质谱。在离子阱和三重四极杆质谱仪上进行分析。在碰撞诱导解离后，结合胆汁酸可与类固醇骨架一起裂解成甘氨酸或牛磺酸相关片段。游离胆汁酸的裂解被进一步阐明，特别是在正离子模式下通过大气压化学电离质谱。除了普遍观察到的中性损失外，首次提出了胆汁酸碳环上发生的消除。此外，四种异构的5 β-胆烷酸羟基衍生物采用负离子模式电喷雾电离区分了3 α，6 α-、3 α，7 β-、3 α，7 α-和3 α，12 α-四种不同的羟基取代基：3 α，7 β-OH取代基倾向于消除H2O和CH 2 O2基团，3 α，6 α-OH取代基倾向于中性损失两个H2O分子; 3 α，12 α-OH取代基易于以CO2分子的形式失去羧基，3 α，7 α-OH取代基在脱水后没有进一步断裂。本研究为胆汁酸的质谱提供了具体的解释。结果可能有助于胆汁酸分析，特别是在临床测定和代谢组学研究。(C)2011 Elsevier Inc. All rights reserved.
Bile acids are steroids with a pentanoic acid substituent at C-17. They are the terminal products of cholesterol excretion, and play critical physiological roles in human and animals. Bile acids are easy to detect but difficult to identify by using mass spectrometry due to their poly-ring structure and various hydroxylation patterns. In this study, fragmentation pathways of 18 free and conjugated bile acids were interpreted by using tandem mass spectrometry. The analyses were conducted on ion trap and triple quadrupole mass spectrometers. Upon collision-induced dissociation, the conjugated bile acids could cleave into glycine or taurine related fragments, together with the steroid skeleton. Fragmentations of free bile acids were further elucidated, especially by atmospheric pressure chemical ionization mass spectrometry in positive ion mode. Aside from universally observed neutral losses, eliminations occurred on bile acid carbon rings were proposed for the first time. Moreover, four isomeric 5 beta-cholanic acid hydroxyl derivatives (3 alpha,6 alpha-, 3 alpha,7 beta-, 3 alpha,7 alpha-, and 3 alpha,12 alpha-) were differentiated using electrospray ionization in negative ion mode: 3 alpha,7 beta-OH substituent inclined to eliminate H2O and CH2O2 groups; 3 alpha,6 alpha-OH substituent preferred neutral loss of two H2O molecules; 3 alpha,12 alpha-OH substituent apt to lose the carboxyl in the form of CO2 molecule; and 3 alpha,7 alpha-OH substituent exhibited no further fragmentation after dehydration. This study provided specific interpretation for mass spectra of bile acids. The results could contribute to bile acid analyses, especially in clinical assays and metabonomic studies. (C) 2011 Elsevier Inc. All rights reserved.