Binata Shrestha, Sujan Koju, Ekata Shrestha
It is critical to have high sensitivity when developing neonatal toxicology and metabolic screening tests to ensure the detection of xenobiotics as well as endogenous analytes in very small sample sizes. Although LC-MS/MS has emerged as the gold standard in this field, there are several complications with developing a panel of diagnostic tests. In this paper, an overview of the latest developments regarding multiplexed LC-MS/MS panels is provided. Specifically, the improvement of the specificity and sensitivity of newborn screening through multiplexing has been addressed with a particular focus on drug therapy monitoring and toxicology. The use of DBS and meconium for the assessment of various xenobiotics has been explored with the use of LC-MS/MS. Based on the current literature on this topic, multiplexing leads to decreased false positive rates and improved detection of lysosomal storage disorders, organic acidemias, and prenatal exposures to substances. In addition, the use of follow-up tests combined with the multi-omics approach allows overcoming the limitations associated with immunoassays. Multiplexed LC-MS/MS is an important tool in neonatal diagnostics, while the integration of artificial intelligence and digital microfluidics will be explored in future studies.