A multiplexed LC-MS/MS assay for comprehensive screening of amino acid metabolism disorders

Advancements in liquid chromatography-tandem mass spectrometry (LC-MS/MS) are redefining the landscape of clinical diagnostics, particularly in the context of newborn screening for inborn errors of metabolism. Conventional analytical platforms are often limited by a small number of analytes and requ...

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Bibliographic Details
Main Authors: Jisha Chandran, Madan Gopal Ramarajan, Vykuntaraju Kammasandra Nanjundagowda, Aruna Gowdra, Jayesh Warade, Anikha Bellad, Kannan Rangiah
Format: Article
Language:English
Published: Elsevier 2025-12-01
Series:Talanta Open
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Online Access:http://www.sciencedirect.com/science/article/pii/S2666831925001250
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Summary:Advancements in liquid chromatography-tandem mass spectrometry (LC-MS/MS) are redefining the landscape of clinical diagnostics, particularly in the context of newborn screening for inborn errors of metabolism. Conventional analytical platforms are often limited by a small number of analytes and require multiple platforms for subsequent analyses, thereby impacting timely diagnosis and management. This study describes the development of a multiplexed targeted mass spectrometry-based assay for simultaneous detection and quantitation of amines, including amino acids and their derivatives, from plasma, urine and dried blood spots. The method utilizes a single step derivatization strategy based on one step click chemistry that simplifies sample preparation while improving analytical sensitivity allowing for detection of analytes at sub-picomolar concentrations. Furthermore, we adopted a strategy of generating heavy isotopically labeled standards by chemically modifying the corresponding light standards using a stable isotope labeled derivatizing agent, enabling their use as internal standards for quantification. This approach can offer a cost-effective and scalable solution for the early detection and management of inherited metabolic disorders, particularly in cases where accurate detection of amines is critical.
ISSN:2666-8319