液相色谱串联质谱法分析人体内儿茶酚胺及其代谢产物的研究进展

Research Progress in the Analysis of Catecholamines and Their Metabolites in Human Body by Liquid Chromatography Tandem Mass Spectrometry

摘要: 儿茶酚胺，包括肾上腺素、去甲肾上腺素和多巴胺，是由酪氨酸在一系列酶的催化作用下合成的。儿茶酚胺通过自主调节在生理活动中发挥重要作用，维持人体的动态平衡。儿茶酚胺及其代谢物的异常浓度(特别是高浓度)常提示神经内分泌肿瘤，特别是嗜铬细胞瘤和副神经节瘤的发生。嗜铬细胞瘤和副神经节瘤的显著特点是不规律地释放儿茶酚胺，有时呈爆炸式释放，以及顽固性高血压。正是由于这些性质，嗜铬细胞瘤和副神经节瘤可出现许多严重的并发症，但目前对嗜铬细胞瘤和副神经节瘤的诊断率很低。原因之一是其临床表现具有高度的异质性和多样性，但更重要的原因是缺乏一种筛选和诊断嗜铬细胞瘤和副神经节瘤的超敏方法。目前，医学组织通常通过检测尿液或血浆中的儿茶酚胺来筛查嗜铬细胞瘤和副神经节瘤。然而，儿茶酚胺及其某些代谢物的浓度低、不稳定、极性高、分子结构高度相似，使得儿茶酚胺的准确定量非常困难。本文概述了儿茶酚胺及其代谢物的检测现状，讨论了液相色谱串联质谱法联合检测儿茶酚胺及其代谢物的必要性，阐述了联合检测方法开发与验证的基本步骤及注意事项。

Abstract: Catecholamine, including epinephrine, norepinephrine and dopamine, is derived from tyrosine by the catalysis of a series of enzymes. Catecholamines take an important role in physiological activity via autonomic regulation and keep a dynamic balance in human body. The abnormal concentration (particularly the high level) of catecholamines and their metabolites often indicates the occurrence of neuron endocrine neoplasm especially pheochromocytoma and paraganglioma. The prominent features of pheochromocytoma and paraganglioma are releasing Catecholamines irregularly and sometimes explosively as well as refractory hypertension. It is because these nature, pheochromocytoma and paraganglioma can present with lots of serious complications. Unfortunately, the diagnosis rate of pheochromocytoma and paraganglioma is very low. One reason is its high heterogeneity and protean clinical presentation, but the more important reason is lacking a hypersensitive method to screen and diagnose pheochromocytoma and paraganglioma. At present, medical organization usually screens pheochromocytoma and paraganglioma by detecting the Catecholamines in urine or plasma. However, low concentration, instability, high polarity and high similarity in molecular structure of some metabolites make it very difficult for accurate quantification of the Catecholamines. In this paper, the detection status of catecholamine and its metabolites is summarized, the necessity of LC-MS/MS combined detection of catecholamine and its metabolites is discussed, and the basic steps and precautions of the development and verification of the combined detection method are explained.