Shigematsu Yosuke, Hata Ikue, Tanaka Yukie
Department of Health Science, Faculty of Medical Sciences, University of Fukui, Fukui 910-1193, Japan.
Clin Chim Acta. 2007 Nov-Dec;386(1-2):82-6. doi: 10.1016/j.cca.2007.08.003. Epub 2007 Aug 19.
Recent neonatal screening for isovaleric acidemia by tandem mass spectrometry based on dried blood-spot levels of C5-acylcarnitines, including isovalerylcarnitine and its isomer, pivaloylcarnitine, which is derived from pivalate-generating antibiotics, has caused many false-positive results. We have developed a method to overcome this interference.
The amounts of isovalerylglycine were determined by a stable-isotope dilution electrospray tandem mass spectrometric analysis, using multiple-reaction monitoring with product ions of m/z 132, which were generated predominantly from quasi-molecular ions of isovalerylglycine butylester but apparently not from those of pivaloylglycine butylester.
Isovalerylglycine concentrations in dried blood spots of control newborns were 0.17+/-0.03 nmol/ml, and those of patients with isovaleric acidemia ranged from 1.3 to 80.0 nmol/ml. Those of the newborns treated with antibiotics, which caused high C5-acylcarnitine levels (1.9+/-1.7 nmol/ml) in dried blood spots, were 0.22+/-0.05 nmol/ml.
Our data showed that the present method is useful in eliminating the false-positive results due to antibiotics use in newborn screening for isovaleric acidemia.
近期通过串联质谱法基于干血斑中C5-酰基肉碱水平（包括异戊酰肉碱及其异构体新戊酰肉碱，后者源自产生新戊酸盐的抗生素）对异戊酸血症进行新生儿筛查时，出现了许多假阳性结果。我们开发了一种方法来克服这种干扰。
采用稳定同位素稀释电喷雾串联质谱分析法，通过多反应监测m/z 132的产物离子来测定异戊酰甘氨酸的含量，这些产物离子主要由异戊酰甘氨酸丁酯的准分子离子产生，而显然不是由新戊酰甘氨酸丁酯的准分子离子产生。
对照新生儿干血斑中的异戊酰甘氨酸浓度为0.17±0.03 nmol/ml，异戊酸血症患者的浓度范围为1.3至80.0 nmol/ml。使用抗生素治疗的新生儿干血斑中C5-酰基肉碱水平较高（1.9±1.7 nmol/ml），其异戊酰甘氨酸浓度为0.22±0.05 nmol/ml。
我们的数据表明，本方法有助于消除新生儿异戊酸血症筛查中因使用抗生素导致的假阳性结果。
