Gelpí E
Department of Medical Bioanalysis, CID-CSIC, Barcelona, Spain.
J Chromatogr A. 1995 May 26;703(1-2):59-80. doi: 10.1016/0021-9673(94)01287-o.
This review centres on the application of various LC-MS and LC-MS-MS techniques to the study and solution of practical problems in biomedical research. For this purpose it covers a selection of publications in this area included in the MEDLINE database for the period 1991-mid-1994. As shown herein, LC-MS is increasingly gaining in importance in the biomedical field, especially after the revolution brought about by the introduction of the new liquid-phase atmospheric pressure ionization (API) techniques, such as electrospray (ES) and ionspray. The information in this database shows that thermospray (TS), which clearly dominated LC-MS coupling in the 1980s, is on a downward trend relative to the more modern API techniques which will certainly dominate this application field in the present decade. Studies on drug metabolism, therapeutic drug monitoring and pharmacology have been traditionally carried out by GC-MS. However, LC-MS has lately been replacing classical GC-MS techniques in many of these applications. For instance, LC-ES-MS has greatly facilitated the application of both qualitative and quantitative LC-MS methods to highly polar molecules. This is possible without the need to resort to elaborate sample handling and derivatization procedures for relatively high-molecular-mass compounds such as drug conjugates, biosynthetic and natural peptides and therapeutic proteins obtained by recombinant DNA technology, all of them formerly totally inaccessible to the standard GC-MS or LC-MS methods. With regard to studies on metabolism and biochemical phenomena of endogenous compounds, LC-ES-MS is also becoming very strong in the analysis of structural biopolymers such as peptides, proteins, glycoproteins and glycolipids, and also lower molecular mass compounds such as fatty acids, vitamins, steroids and nucleic acids. For example, structural verification of post-translational modifications in proteins can be efficiently obtained in the time frame of an LC run and suitable MS methods for the location of glycopeptide-containing fractions in proteolytic digests of glycoproteins have been developed. Interesting examples are also shown of the use of LC-MS in clinical studies and the determination of biological markers of disease.
本综述聚焦于各种液相色谱 - 质谱联用（LC-MS）和液相色谱 - 串联质谱联用（LC-MS-MS）技术在生物医学研究中实际问题的研究与解决中的应用。为此，它涵盖了1991年至1994年年中MEDLINE数据库中该领域的部分出版物。如本文所示，液相色谱 - 质谱联用在生物医学领域的重要性日益增加，特别是在引入新的液相大气压电离（API）技术（如电喷雾（ES）和离子喷雾）带来变革之后。该数据库中的信息表明，在20世纪80年代明显主导液相色谱 - 质谱联用的热喷雾（TS），相对于更现代的API技术呈下降趋势，而后者肯定会在本十年主导这一应用领域。药物代谢、治疗药物监测和药理学研究传统上是通过气相色谱 - 质谱联用（GC-MS）进行的。然而，液相色谱 - 质谱联用最近在许多这些应用中正在取代传统的气相色谱 - 质谱联用技术。例如，液相色谱 - 电喷雾 - 质谱联用（LC-ES-MS）极大地促进了定性和定量液相色谱 - 质谱方法对高极性分子的应用。对于相对高分子质量的化合物，如药物缀合物、生物合成和天然肽以及通过重组DNA技术获得的治疗性蛋白质，无需采用复杂的样品处理和衍生化程序即可实现这一点，而这些化合物以前完全无法用标准的气相色谱 - 质谱联用或液相色谱 - 质谱联用方法分析。关于内源性化合物的代谢和生化现象的研究，液相色谱 - 电喷雾 - 质谱联用在分析结构生物聚合物（如肽、蛋白质、糖蛋白和糖脂）以及较低分子量的化合物（如脂肪酸、维生素、类固醇和核酸）方面也变得非常强大。例如，蛋白质翻译后修饰的结构验证可以在液相色谱运行的时间范围内有效地获得，并且已经开发出合适的质谱方法用于在糖蛋白的蛋白水解消化物中定位含糖肽的部分。还展示了液相色谱 - 质谱联用在临床研究中的有趣应用实例以及疾病生物标志物的测定。
