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Analytical chemistry
02 13, 2024;96 (6): 2666-2675.

Three-Minute Enantioselective Amino Acid Analysis by Ultra-High-Performance Liquid Chromatography Drift Tube Ion Mobility-Mass Spectrometry Using a Chiral Core-Shell Tandem Column Approach.

Simon Jonas Jaag, Younes Valadbeigi, Tim Causon, Harald Gross, Michael Lämmerhofer
Author Information
  1. Simon Jonas Jaag: Pharmaceutical (Bio-)Analysis, Institute of Pharmaceutical Sciences, University of Tuebingen, Auf der Morgenstelle 8, 72076 Tuebingen, Germany.
  2. Younes Valadbeigi: Department of Chemistry, Faculty of Science, Imam Khomeini International University, Nowrouzian, 3414896818 Qazvin, Iran.
  3. Tim Causon: University of Natural Resources and Life Sciences, Vienna Department of Chemistry, Institute of Analytical Chemistry, Muthgasse 18, 1190 Vienna, Austria. ORCID
  4. Harald Gross: Pharmaceutical Biology, Institute of Pharmaceutical Sciences, University of Tuebingen, Auf der Morgenstelle 8, 72076 Tuebingen, Germany. ORCID
  5. Michael Lämmerhofer: Pharmaceutical (Bio-)Analysis, Institute of Pharmaceutical Sciences, University of Tuebingen, Auf der Morgenstelle 8, 72076 Tuebingen, Germany.
PMID: 38297457 DOI: 10.1021/acs.analchem.3c05426

Abstract

Fast liquid chromatography (LC) amino acid enantiomer separation of 6-aminoquinolyl--hydroxysuccinimidyl carbamate (AQC) derivatives using a chiral core-shell particle tandem column with weak anion exchange and zwitterionic-type quinine carbamate selectors in less than 3 min was achieved. Enantiomers of all AQC-derivatized proteinogenic amino acids and some isomeric ones (24 in total plus achiral glycine) were baseline separated ( > 1.5 except for glutamic acid with = 1.3), while peaks of distinct amino acids and structural isomers (constitutional isomers and diastereomers of leucine and threonine) of the same configuration overlapped to various degrees. For this reason, drift tube ion mobility-mass spectrometry was added (i.e., LC-IM-MS) as an additional selectivity filter without extending run time. The IM separation dimension in combination with high-resolution demultiplexing enabled confirmation of threonine isomers (threonine, -threonine, homoserine), while leucine, isoleucine, and -isoleucine have almost identical collisional cross-section () values and added no selectivity to the partial LC separation. Density functional theory (DFT) calculations show that IM separation of threonine isomers was possible due to conformational stabilization by hydrogen bond formation between the hydroxyl side chain and the urea group. Generally, the CCS of protonated ions increased uniformly with addition of the AQC label, while outliers could be explained by consideration of intramolecular interactions and additional structural analysis. Preliminary validation of the enantioselective LC-IM-MS method for quantitative analysis showed compliance of accuracy and precision with common limits in bioanalytical methods, and applicability to a natural lipopeptide and a therapeutic synthetic peptide could be demonstrated.

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MeSH Term

Amino Acids
Chromatography, High Pressure Liquid
Stereoisomerism
Leucine
Isoleucine
Liquid Chromatography-Mass Spectrometry
Threonine
Ions

Chemicals

Amino Acids
Leucine
Isoleucine
Threonine
Ions
Journal Article Research Support, Non-U.S. Gov't
Article has an altmetric score of 2

Word Cloud

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