Tsikas D
Institute of Clinical Pharmacology, Hannover Medical School, Germany.
J Chromatogr B Biomed Sci Appl. 1998 Oct 9;717(1-2):201-45. doi: 10.1016/s0378-4347(98)00210-2.
Prostaglandins, thromboxane, leukotrienes, isoprostanes and other arachidonic acid metabolites are structurally closely related, potent, biologically active compounds. One of the most challenging tasks in eicosanoids research has been to define the role of the various eicosanoids in human health and disease, and to monitor the effects of drugs on the in vivo synthesis of these lipid mediators in man. Great advances in instrumentation and ionization techniques, in particular the development of tandem mass spectrometry and negative-ion chemical ionization (NICI), in gas chromatography and also advances in methodologies for solid-phase extraction and sample purification by thin-layer chromatography and high-performance liquid chromatography have been made. Now gas chromatography-mass spectrometry (GC-MS) and GC-tandem MS in the NICI mode are currently indispensable analytical tools for reliable routine quantitation of eicosanoid formation in vivo in humans. In this article analytical methods for eicosanoids based on GC-MS and GC-tandem MS are reviewed emphasizing the quantitative measurement of specific index metabolites in human urine and its importance in clinical studies in man. Aspects of method validation and quality control are also discussed.
前列腺素、血栓素、白三烯、异前列腺素及其他花生四烯酸代谢产物是结构密切相关的强效生物活性化合物。类二十烷酸研究中最具挑战性的任务之一,是确定各种类二十烷酸在人类健康和疾病中的作用,并监测药物对人体这些脂质介质体内合成的影响。在仪器和电离技术方面取得了巨大进展,特别是串联质谱和负离子化学电离(NICI)的发展、气相色谱技术,以及固相萃取和通过薄层色谱和高效液相色谱进行样品纯化方法的进步。现在,气相色谱-质谱联用(GC-MS)和NICI模式下的GC-串联质谱是可靠地常规定量人体体内类二十烷酸形成不可或缺的分析工具。本文综述了基于GC-MS和GC-串联质谱的类二十烷酸分析方法,重点强调了人尿中特定指标代谢产物的定量测定及其在人体临床研究中的重要性。还讨论了方法验证和质量控制方面的问题。