Rapid Enantiomeric Ratio Determination of Multiple Amino Acids Using Ion Mobility-Mass Spectrometry

Chiral analysis is becoming increasingly important across various scientific fields, including chemistry, pharmaceuticals, biosciences, and more recently, metabolomics. In this context, a high-resolution and high-throughput method was developed for the simultaneous determination of the enantiomeric...

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Main Authors: Wenqing Xu, Estelle Rathahao-Paris, Sandra Alves
Format: Article
Language:English
Published: MDPI AG 2025-06-01
Series:Molecules
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Online Access:https://www.mdpi.com/1420-3049/30/12/2497
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author Wenqing Xu
Estelle Rathahao-Paris
Sandra Alves
author_facet Wenqing Xu
Estelle Rathahao-Paris
Sandra Alves
author_sort Wenqing Xu
collection DOAJ
description Chiral analysis is becoming increasingly important across various scientific fields, including chemistry, pharmaceuticals, biosciences, and more recently, metabolomics. In this context, a high-resolution and high-throughput method was developed for the simultaneous determination of the enantiomeric ratio (<i>er</i>) of seven pairs of amino acid (AA) enantiomers (Arg, Gln, His, Met, Pro, Tyr, and Trp) using flow injection analysis coupled with ion mobility-mass spectrometry (FIA-IM-MS) technology. Specifically, the Single Ion Mobility Monitoring (SIM<sup>2</sup>) mode on a TIMS-Tof<sup>TM</sup> instrument enabled the rapid relative quantification of chiral compound mixtures. A linear model accurately described the relationship between enantiomeric ratio and IM-MS response for Arg, Gln, and Pro enantiomers, as evidenced by high R<sup>2</sup> values and unbiased residuals. In contrast, non-linear trends were observed for His, Tyr, and Trp, where a quadratic model significantly improved the fit. However, the linear model was retained for Met, despite an R<sup>2</sup> of about 0.98, due to its comparable performance and simplicity. Measurement accuracy was confirmed with very good recovery rates for <i>er</i> values of 0.95 and 0.99 across all AAs. Finally, the potential of the FIA-SIM<sup>2</sup>-MS approach in chiral analysis was demonstrated, particularly its ability to provide a reliable and efficient high-throughput tool for accurate <i>er</i> determination.
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spelling doaj-art-de7308ebc9064d13ae72a60c1e5b01252025-08-20T03:27:36ZengMDPI AGMolecules1420-30492025-06-013012249710.3390/molecules30122497Rapid Enantiomeric Ratio Determination of Multiple Amino Acids Using Ion Mobility-Mass SpectrometryWenqing Xu0Estelle Rathahao-Paris1Sandra Alves2Sorbonne Université, Faculté des Sciences et de l’Ingénierie, Institut Parisien de Chimie Moléculaire (IPCM), 75005 Paris, FranceSorbonne Université, Faculté des Sciences et de l’Ingénierie, Institut Parisien de Chimie Moléculaire (IPCM), 75005 Paris, FranceSorbonne Université, Faculté des Sciences et de l’Ingénierie, Institut Parisien de Chimie Moléculaire (IPCM), 75005 Paris, FranceChiral analysis is becoming increasingly important across various scientific fields, including chemistry, pharmaceuticals, biosciences, and more recently, metabolomics. In this context, a high-resolution and high-throughput method was developed for the simultaneous determination of the enantiomeric ratio (<i>er</i>) of seven pairs of amino acid (AA) enantiomers (Arg, Gln, His, Met, Pro, Tyr, and Trp) using flow injection analysis coupled with ion mobility-mass spectrometry (FIA-IM-MS) technology. Specifically, the Single Ion Mobility Monitoring (SIM<sup>2</sup>) mode on a TIMS-Tof<sup>TM</sup> instrument enabled the rapid relative quantification of chiral compound mixtures. A linear model accurately described the relationship between enantiomeric ratio and IM-MS response for Arg, Gln, and Pro enantiomers, as evidenced by high R<sup>2</sup> values and unbiased residuals. In contrast, non-linear trends were observed for His, Tyr, and Trp, where a quadratic model significantly improved the fit. However, the linear model was retained for Met, despite an R<sup>2</sup> of about 0.98, due to its comparable performance and simplicity. Measurement accuracy was confirmed with very good recovery rates for <i>er</i> values of 0.95 and 0.99 across all AAs. Finally, the potential of the FIA-SIM<sup>2</sup>-MS approach in chiral analysis was demonstrated, particularly its ability to provide a reliable and efficient high-throughput tool for accurate <i>er</i> determination.https://www.mdpi.com/1420-3049/30/12/2497chiral analysisenantiomeric ratioion mobility-mass spectrometryflow injection analysis
spellingShingle Wenqing Xu
Estelle Rathahao-Paris
Sandra Alves
Rapid Enantiomeric Ratio Determination of Multiple Amino Acids Using Ion Mobility-Mass Spectrometry
Molecules
chiral analysis
enantiomeric ratio
ion mobility-mass spectrometry
flow injection analysis
title Rapid Enantiomeric Ratio Determination of Multiple Amino Acids Using Ion Mobility-Mass Spectrometry
title_full Rapid Enantiomeric Ratio Determination of Multiple Amino Acids Using Ion Mobility-Mass Spectrometry
title_fullStr Rapid Enantiomeric Ratio Determination of Multiple Amino Acids Using Ion Mobility-Mass Spectrometry
title_full_unstemmed Rapid Enantiomeric Ratio Determination of Multiple Amino Acids Using Ion Mobility-Mass Spectrometry
title_short Rapid Enantiomeric Ratio Determination of Multiple Amino Acids Using Ion Mobility-Mass Spectrometry
title_sort rapid enantiomeric ratio determination of multiple amino acids using ion mobility mass spectrometry
topic chiral analysis
enantiomeric ratio
ion mobility-mass spectrometry
flow injection analysis
url https://www.mdpi.com/1420-3049/30/12/2497
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AT estellerathahaoparis rapidenantiomericratiodeterminationofmultipleaminoacidsusingionmobilitymassspectrometry
AT sandraalves rapidenantiomericratiodeterminationofmultipleaminoacidsusingionmobilitymassspectrometry