Liquid Chromatography–Tandem Mass Spectrometry in Newborn Screening Laboratories
Michael H. Gelb, Khaja Basheeruddin, Alberto Burlina, Hsiao-Jan Chen, Yin‐Hsiu Chien, George J. Dizikes, M. Christine Dorley, Roberto Giugliani, Amy Hietala, Xinying Hong, Shu‐Min Kao, Hamid Khaledi, Tracy Klug, Francyne Kubaski, Hsuan-Chieh Liao, Monica Martin, Adrienne Manning, Joseph J. Orsini, Yin Peng, Enzo Ranieri, Andreas Rohrwasser, Nicolas Szabo‐Fresnais, Coleman Turgeon, Frédéric M. Vaz, Liyun Wang, Dietrich Matern
Abstract
Tandem mass spectrometry (MS/MS) is the most universal platform currently available for the analysis of enzymatic activities and biomarkers in dried blood spots (DBS) for applications in newborn screening (NBS). Among the MS/MS applications in NBS, the most common is flow-injection analysis (FIA-) MS/MS, where the sample is introduced as a bolus injection into the mass spectrometer without the prior fractionation of analytes. Liquid chromatography combined with MS/MS (LC-MS/MS) has been employed for second-tier tests to reduce the false-positive rate associated with several nonspecific screening markers, beginning two decades ago. More recently, LC-MS/MS has been applied to primary screening for new conditions for which FIA-MS/MS or other methods, including genomic screening, are not yet adequate. In addition to providing a list of the currently used LC-MS/MS-based assays for NBS, the authors share their experience regarding the maintenance requirements of LC-MS/MS vs. FIA-MS/MS systems. The consensus is that the maintenance of LC-MS/MS and FIA-MS/MS instrumentation is similar, and LC-MS/MS has the advantage of allowing for a larger number of diseases to be screened for in a multiplex, cost-effective fashion with a high throughput and an adequate turnaround time.