Britz-McKibbin Philip
Department of Chemistry and Chemical Biology, McMaster University, Hamilton, ON, Canada.
Methods Mol Biol. 2013;919:43-56. doi: 10.1007/978-1-62703-029-8_5.
Expanded newborn screening of inborn errors of metabolism (IEM) based on tandem mass spectrometry technology has emerged as one of the most successful preventative healthcare initiatives for presymptomatic diagnosis and treatment of rare yet treatable genetic diseases. However, confirmatory testing using methods with improved specificity is required in clinical laboratories to improve the positive predictive value for certain classes of IEMs due to their high rates of false positives. Here, we describe recent advances for comprehensive profiling of amino acids and acylcarnitines derived from dried blood spot extracts or plasma using capillary electrophoresis-electrospray ionization-mass spectrometry (CE-ESI-MS) that allows for resolution of major isobaric/isomeric interferences without complicated sample handling. The integration of online sample preconcentration together with desalting in CE-ESI-MS enables the direct analysis of hydrophilic amino acids, surface-active acylcarnitines, as well as labile thiols under a single format when using a simple aqueous buffer electrolyte system.
基于串联质谱技术的扩大新生儿遗传代谢病筛查已成为针对罕见但可治疗的遗传疾病进行症状前诊断和治疗的最成功的预防性医疗举措之一。然而，由于某些类型的遗传代谢病假阳性率较高，临床实验室需要使用特异性更高的方法进行确证检测，以提高其阳性预测值。在此，我们描述了使用毛细管电泳-电喷雾电离-质谱（CE-ESI-MS）对干血斑提取物或血浆中的氨基酸和酰基肉碱进行全面分析的最新进展，该方法无需复杂的样品处理即可解决主要的等压/同分异构干扰。在CE-ESI-MS中，在线样品预浓缩与脱盐相结合，使用简单的水性缓冲电解质系统，能够在单一模式下直接分析亲水性氨基酸、表面活性酰基肉碱以及不稳定的硫醇。
