TY - JOUR
T1 - Liquid Chromatography–Tandem Mass Spectrometry in Newborn Screening Laboratories
AU - Gelb, Michael H.
AU - Basheeruddin, Khaja
AU - Burlina, Alberto
AU - Chen, Hsiao-Jan
AU - Chien, Yin-Hsiu
AU - Dizikes, George
AU - Dorley, Christine
AU - Giugliani, Roberto
AU - Hietala, Amy
AU - Hong, Xinying
AU - Kao, Shu-Min
AU - Khaledi, Hamid
AU - Klug, Tracy
AU - Kubaski, Francyne
AU - Liao, Hsuan-Chieh
AU - Martin, Monica
AU - Manning, Adrienne
AU - Orsini, Joseph
AU - Peng, Yin
AU - Ranieri, Enzo
AU - Rohrwasser, Andreas
AU - Szabo-Fresnais, Nicolas
AU - Turgeon, Coleman T.
AU - Vaz, Frédérick M.
AU - Wang, Li-Yun
AU - Matern, Dietrich
N1 - Funding Information: This work was supported in part by an appointment to the Research Participation Program at CDC by the Oak Ridge Institute for Science and Education through an interagency agreement between the US Department of Energy and CDC (to J.R.S.) and by the National Institutes of Health Loan Repayment Award (to J.R.S.). Publisher Copyright: © 2022 by the authors.
PY - 2022/12/1
Y1 - 2022/12/1
N2 - 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.
AB - 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.
KW - dried blood spots
KW - inborn errors of metabolism
KW - liquid chromatography
KW - newborn screening
KW - reflex testing
KW - tandem mass spectrometry
UR - http://www.scopus.com/inward/record.url?scp=85144735897&partnerID=8YFLogxK
U2 - https://doi.org/10.3390/ijns8040062
DO - https://doi.org/10.3390/ijns8040062
M3 - Review article
C2 - 36547379
SN - 2409-515X
VL - 8
JO - International Journal of Neonatal Screening
JF - International Journal of Neonatal Screening
IS - 4
M1 - 62
ER -