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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| Format: | Article |
| Language: | English |
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Elsevier
2025-12-01
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| Series: | Talanta Open |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2666831925001250 |
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| author | Jisha Chandran Madan Gopal Ramarajan Vykuntaraju Kammasandra Nanjundagowda Aruna Gowdra Jayesh Warade Anikha Bellad Kannan Rangiah |
| author_facet | Jisha Chandran Madan Gopal Ramarajan Vykuntaraju Kammasandra Nanjundagowda Aruna Gowdra Jayesh Warade Anikha Bellad Kannan Rangiah |
| author_sort | Jisha Chandran |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-7c1a8d921e334cf6b3e2e2f667f8d68c |
| institution | DOAJ |
| issn | 2666-8319 |
| language | English |
| publishDate | 2025-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Talanta Open |
| spelling | doaj-art-7c1a8d921e334cf6b3e2e2f667f8d68c2025-08-20T02:55:31ZengElsevierTalanta Open2666-83192025-12-011210052310.1016/j.talo.2025.100523A multiplexed LC-MS/MS assay for comprehensive screening of amino acid metabolism disordersJisha Chandran0Madan Gopal Ramarajan1Vykuntaraju Kammasandra Nanjundagowda2Aruna Gowdra3Jayesh Warade4Anikha Bellad5Kannan Rangiah6Manipal Academy of Higher Education, Manipal, Karnataka, India; Institute of Bioinformatics, Bangalore, Karnataka, IndiaManipal Academy of Higher Education, Manipal, Karnataka, India; Institute of Bioinformatics, Bangalore, Karnataka, IndiaIndira Gandhi Institute of Child Health, Bangalore, Karnataka, IndiaIndira Gandhi Institute of Child Health, Bangalore, Karnataka, IndiaMeenakshi Mission Hospital and Research Centre, Madurai, Tamil Nadu, IndiaManipal Academy of Higher Education, Manipal, Karnataka, India; Institute of Bioinformatics, Bangalore, Karnataka, IndiaManipal Academy of Higher Education, Manipal, Karnataka, India; Institute of Bioinformatics, Bangalore, Karnataka, India; Corresponding author.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.http://www.sciencedirect.com/science/article/pii/S2666831925001250Amino acidAminesQuantificationLC-MSNewborn ScreeningInborn errors of metabolism |
| spellingShingle | Jisha Chandran Madan Gopal Ramarajan Vykuntaraju Kammasandra Nanjundagowda Aruna Gowdra Jayesh Warade Anikha Bellad Kannan Rangiah A multiplexed LC-MS/MS assay for comprehensive screening of amino acid metabolism disorders Talanta Open Amino acid Amines Quantification LC-MS Newborn Screening Inborn errors of metabolism |
| title | A multiplexed LC-MS/MS assay for comprehensive screening of amino acid metabolism disorders |
| title_full | A multiplexed LC-MS/MS assay for comprehensive screening of amino acid metabolism disorders |
| title_fullStr | A multiplexed LC-MS/MS assay for comprehensive screening of amino acid metabolism disorders |
| title_full_unstemmed | A multiplexed LC-MS/MS assay for comprehensive screening of amino acid metabolism disorders |
| title_short | A multiplexed LC-MS/MS assay for comprehensive screening of amino acid metabolism disorders |
| title_sort | multiplexed lc ms ms assay for comprehensive screening of amino acid metabolism disorders |
| topic | Amino acid Amines Quantification LC-MS Newborn Screening Inborn errors of metabolism |
| url | http://www.sciencedirect.com/science/article/pii/S2666831925001250 |
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