通过串联质谱法对干血斑中的甲状腺素（T4）进行快速代谢和新生儿筛查。

Rapid metabolic and newborn screening of thyroxine (T4) from dried blood spots by MS/MS.

作者信息

Chace Donald H, Singleton Scott, Diperna James, Aiello Mauro, Foley Thomas

机构信息

Pediatrix Analytical, The Pediatrix Center for Research and Education 1301 Concord Terrace Sunrise, FL 33323, United States.

出版信息

Clin Chim Acta. 2009 May;403(1-2):178-83. doi: 10.1016/j.cca.2009.02.012. Epub 2009 Feb 28.

DOI:10.1016/j.cca.2009.02.012

PMID:19254705

Abstract

BACKGROUND

Thyroxin (T(4)) plays an important role in the regulation of the rate of metabolism of proteins, fats, and carbohydrates. Congenital hypothyroidism, an inherited deficiency of thyroid hormones, is screened in newborns using a variety of methods that include total T(4) or thyroid stimulating hormone (TSH). Some laboratories measure either total T(4) or TSH as a means of detecting infants with hypothyroidism with a subset that analyzes both total T(4) and TSH as a primary screen or a combination of primary and secondary screens.

METHODS

We have developed a new MS/MS method that measures T(4) from a filter paper blood spot following methanol extraction using the essentially the same method as MS/MS analysis of amino acids. Product ion spectra show a transition of 833.8-->731.8 (102 Da). An SRM for T(4) and (13)C(6)-T(4) was added to the MS/MS analysis of acylcarnitines and amino acids.

RESULTS

Analysis of T(4) by MS/MS compares well with the immunoassay. The mean of 10,225 newborn screening specimens was 14.4 microg/dl (range 2.4-33) for MS/MS and 16.9 microg/dl (range 1.4-71.8) for AutoDELFIA. The MS/MS assay was linear with a correlation coefficient of 0.998. Regression analysis of MS/MS with the AutoDELFIA had a slope of 0.7, a y-intercept of 3.25, and a correlation coefficient of 0.727. We determined a MS/MS detection limit of 0.97 microg/dl and a lower LoQ (limit of quantification) of 2 microg/dl.

CONCLUSION

This method may provide a cost effective means of analyzing both T(4) and TSH by consolidating a T(4) analysis into the MS/MS panel.

摘要

背景

甲状腺素（T4）在调节蛋白质、脂肪和碳水化合物的代谢速率方面发挥着重要作用。先天性甲状腺功能减退症是一种遗传性甲状腺激素缺乏症，通过多种方法对新生儿进行筛查，这些方法包括总T4或促甲状腺激素（TSH）。一些实验室测量总T4或TSH以检测甲状腺功能减退症婴儿，还有一部分实验室将总T4和TSH分析作为主要筛查手段，或作为一级和二级筛查的组合。

方法

我们开发了一种新的串联质谱（MS/MS）方法，该方法使用与氨基酸MS/MS分析基本相同的方法，从甲醇提取后的滤纸血斑中测量T4。产物离子谱显示出833.8→731.8（102 Da）的跃迁。将T4和（13）C6 - T4的选择反应监测（SRM）添加到酰基肉碱和氨基酸的MS/MS分析中。

结果

通过MS/MS对T4进行的分析与免疫测定法具有良好的可比性。10225份新生儿筛查标本的MS/MS平均值为14.4μg/dl（范围2.4 - 33），AutoDELFIA法的平均值为16.9μg/dl（范围1.4 - 71.8）。MS/MS测定呈线性，相关系数为0.998。MS/MS与AutoDELFIA的回归分析斜率为0.7，y轴截距为3.25，相关系数为0.727。我们确定MS/MS的检测限为0.97μg/dl，较低的定量限（LoQ）为2μg/dl。