Development of derivatization reagents bearing chiral 4-imidazolidinone for distinguishing primary amines from other amino acids and application to the liquid chromatography-tandem mass spectrometric analysis of miso

We designed and synthesized three novel derivatization reagents bearing chiral 4-imidazolidinone, namely succinimidyl 2-(3-((benzyloxy)carbonyl)-1-methyl, ethyl, and -phenyl-5-oxoimidazolidin-4-yl)acetates (CIMs), for use in liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis. The CIMs were able to discriminate primary amines from other compounds such as secondary amines and phenols, based on their unique m/z reduction of precursor ion to form product ion in MS/MS. As amino acid derivatization reagents, the CIMs were compared in terms of enantioseparation of amino acid and detection sensitivity. CIMa-OSu with 1-methyl-5-oxoimidazolidinone moiety gave the best optical resolution and detection sensitivity among the CIM reagents. Next, we applied (R)-CIMa-OSu to determine amino acids in miso by LC-triple-quadrupole MS. The proposed method achieved simultaneous determination of 20 L-amino acids and two D-amino acids (D-alanine and D-serine) in the sample with a high sensitivity (limits of detection 5-238 fmol, signal-to-noise ratio 3.3). After derivatization with CIMa-OSu, it was possible to determine whether each peak in the chromatogram was a component of primary amine or not, by using a high-resolution orbitrap MS instrument. (C) 2021 Elsevier B.V. All rights reserved.

Automated summary

Three novel derivatization reagents containing chiral 4-imidazolidinone were designed and synthesized for LC-MS/MS analysis, showing good performance in enantioseparation of amino acids and detection sensitivity. The optimal reagent (CIMa-OSu) was able to simultaneously determine the content of multiple amino acids in samples.