THE ANALYSIS OF DIAGNOSTIC MARKERS OF GENETIC-DISORDERS IN HUMAN BLOOD AND URINE USING TANDEM MASS-SPECTROMETRY WITH LIQUID SECONDARY ION MASS-SPECTROMETRY
THE ANALYSIS OF DIAGNOSTIC MARKERS OF GENETIC-DISORDERS IN HUMAN BLOOD AND URINE USING TANDEM MASS-SPECTROMETRY WITH LIQUID SECONDARY ION MASS-SPECTROMETRY
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DOI：
10.1016/0168-1176(91)85056-r
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发表时间：
1991-12-16
影响因子：
1.8
通讯作者：
CHACE, DH
中科院分区：
文献类型：
--
作者：
MILLINGTON, DS;KODO, N;CHACE, DH
已经开发了一种基于通过快原子轰击或液体二次离子串联质谱（FAB-MS-MS或LISMS-MS）分析体液中的特征代谢物来快速诊断代谢性疾病的方法。通过简单的溶剂提取、酯化和使用三重四极杆质谱仪上的前体离子扫描功能的分析，从100 μ l尿液、200 μ l血浆或25 μ l全血点样到滤纸上获得酰基肉毒碱谱。通过向液体基质中加入少量辛基硫酸钠，使其与酰基肉毒碱酯形成离子对，提高了特异性和灵敏度。使用不同的前体离子扫描功能，将尿液中的酰基甘氨酸作为一组进行特异性检测。通过形成甲酯，通过应用交替扫描功能在相同的样品加载中实现酰基肉毒碱和酰基甘氨酸的代谢谱。通过使用稳定的同位素标记的内标物实现了对所选代谢物的定量分析。使用丁基酯和中性损失扫描功能从100 μ l血浆和25 μ l全血点获得氨基酸谱。采用稳定同位素稀释法对样品中的苯丙氨酸和酪氨酸进行定量分析。这种能力将有助于苯丙酮尿症和其他氨基酸的诊断。这些新方法具有速度、准确性和自动化能力的要求，是大规模新生儿先天性代谢缺陷筛查所必需的。
A method has been developed for the rapid diagnosis of metabolic diseases based on the analysis of characteristic metabolites in body fluids by fast atom bombardment or liquid secondary ion tandem mass spectrometry (FAB-MS-MS or LISMS-MS). Acylcarnitine profiles were obtained from 100-mu-l urine, 200-mu-l plasma or 25-mu-l whole blood spotted onto filter paper by simple solvent extraction, esterification and analysis using a precursor ion scan function on a triple quadrupole mass spectrometer. Specificity and sensitivity were improved by adding a small percentage of sodium octyl sulfate to the liquid matrix, which forms ion pairs with acylcarnitine esters. Acylglycines in urine were specifically detected as a group using a different precursor ion scan function. By forming methyl esters, metabolic profiles of both acylcarnitines and acylglycines were achieved in the same sample loading by application of alternating scan functions. Quantitative analysis of selected metabolites was achieved by use of stable isotope-labeled internal standards. Amino acid profiles were obtained from 100-mu-l plasma and 25-mu-l whole blood spots using butyl esters and a neutral loss scan function. The quantitative analysis of phenylalanine and tyrosine was achieved in these samples using stable isotope dilution. This capability will facilitate the diagnosis of phenylketonuria and other amino acidemias. These new methods have the requirements of speed, accuracy and capability for automation necessary for large-scale neonatal screening of inborn errors of metabolism.