小中大推荐一本书,"Mass Spectrometry in Drug Discovery",里面对液质联用有详细的介绍,从液质联用在药物研发中的应用,质谱的离子源,如何做液质联用,化合物在质谱中的断裂机理,样品前处理,液质联用在药代、组合化学、体外样品分析中的应用都有详细的介绍,这本书是几个大药厂的作者写的,很实用!
"Mass Spectrometry in Drug Discovery" edited by David T. Rossi & Michael W. Sinz (2002) ISBN 0-8247060-7-2.
This state-of-the-art reference summarizes the theory, instrumentation, and application of mass spectrometry and atmospheric pressure ionization to screen, evaluate, and improve the performance and quality of drug candidates梠ffering current techniques in pharmaceutics and pharmacokinetics for increased quantities of new pharmaceutical compounds. Providing time- and cost-efficient approaches for the generation and analysis of effective pharmaceuticals, Mass Spectrometry in Drug Discovery covers o recent advances in combinatorial chemistry, molecular biology, bioanalysis automation, and computing o cassette dosing in drug discovery o the utilization of liquid chromatography/mass spectrometry (LC/MS) in chemical library characterization, combinatorial chemistry, drug transport, and in vivo microdialysis o reliable methods of sample preparation and handling o novel strategies to determine and characterize metabolite structures o the impact of absorption, distribution, metabolism, and elimination properties on drug discovery o the latest research using stable-labeled compounds Demonstrating the use of mass spectrometry in the assessment of disease states, drug targets, and potential drug agents, Mass Spectrometry in Drug Discovery is an invaluable source for spectrometrists; pharmacologists; analytical, medicinal, and organic chemists and biochemists; biotechnologists; pharmaceutical scientists; toxicologists; and upper-level undergraduate and graduate students in these disciplines.
结合书上看的和个人的理解讲讲液质联用的前处理(主要针对药物方面的)。
主要的预处理方法有:
1,直接稀释(适合基质简单的样品,如制剂样品)
2,蛋白沉淀(适合极性较强的化合物,一般用甲醇或乙腈作为沉淀剂)
3,液液萃取(适合大部分化合物,可以选择一系列的提取试剂,极性强的一般选用:乙酸乙酯,非极性强的一般选用:叔丁基甲醚。根据化合物的酸碱性,在提取的时候加缓冲液调解pH值,以提高回收率)
4,固相萃取(适合大部分化合物,成本比较高)
5,在线处理(发文章时常用,实际应用较少)