Enantioselective metabolomics by liquid chromatography-mass spectrometry

A Facile and High-Sensitivity Method for Determining Proteinogenic Amino Acid Enantiomers by Integrating Chiral Phosphinate Derivatizing, 31P NMR and Parallel Reaction Monitoring

“…To date, numerous methods have been developed to discriminate chiral AAs, including chiral stationary phases (CSP), 2/3-D HPLC, chiral derivatizing agents (CDAs), etc. − Recent reviews have comprehensively summarized the state-of-the-art approaches in chiral metabolomics spanning indirect and direct methods. , CDAs have a few incomparable preponderances that, while compared with CSP, it is capable of tolerating a larger coverage of chiral metabolites, improving the separation factors of analytes as well as detectability, etc. ,,, For instance, Marfey’s reagent (FDDA), NIFE reagent, etc. have been extensively adopted which dramatically enhance the sensitivity of analytes in fluorescence .…”

“…8−11 Recent reviews have comprehensively summarized the state-of-the-art approaches in chiral metabolomics spanning indirect and direct methods. 1,2 CDAs have a few incomparable preponderances that, while compared with CSP, it is capable of tolerating a larger coverage of chiral metabolites, improving the separation factors of analytes as well as detectability, etc. 1,2,10,11 For instance, Marfey's reagent (FDDA), NIFE reagent, etc.…”

“…might happen during or after derivatization. 1,10 Recently, an important issue has been revealed by Shimbo et al that the hydrolysis of Nhydroxysuccinimide (NHS) ester results in the formation of an isomer of Asp which has near retention time with Asp and increases the complexity of MS spectra. 13 NHS is a frequently encountered moiety in a lot of derivatizing agents as the leaving group.…”

Comprehensive Online Reversed-Phase × Chiral Two-Dimensional Liquid Chromatography-Mass Spectrometry with Data-Independent Sequential Window Acquisition of All Theoretical Fragment-Ion Spectra-Acquisition for Untargeted Enantioselective Amino Acid Analysis

“…They are also present in (natural, synthetic, and therapeutic) peptides, requiring their analytical determination as part of structure elucidation and/or quality control . A direct enantioresolution of underivatized and derivatized AAs using chiral stationary phases is nowadays the first choice. − Common examples for achiral precolumn derivatization supporting chiral separation comprise 6-aminoquinolyl- N -hydroxysuccinimidyl carbamate (AQC), , 1-fluoro-2,4-dinitrobenzene (DNB-F, Sanger’s reagent), 4-fluoro-7-nitro-2,1,3-benzoxadiazole (NBD), dansyl chloride (Dns), , and 9-fluorenylmethyl-chloroformate (Fmoc-Cl). − These reagents commonly improve the retention and enantioselective behavior, , introduce chromophoric and fluorophoric detectability, can enhance detection sensitivity of AAs with poor electrospray ionization efficiency, and deliver signature ions (in MS/MS detection). , Chiral stationary phases, the workhorses for direct HPLC enantiomer separation, have often remarkable enantioselectivity, but suffer from limited chemoselectivity and lower efficiencies (compared to highly efficient RP congeners). , Hence, the combination of the two principles is quite obvious and should lead to an enhanced separation technology platform.…”

Indirect Enantioseparations: Recent Advances in Chiral Metabolomics for Biomedical Research

“…The last comprehensive review regarding the indirect chiral analysis of proteinogenic amino acids and related metabolites was published in 2008 by Ilisz et al [34]. Since then, this topic has been partially covered by other reviews, with some focusing on the chiral separation of amino acids [35][36][37], some on the role of some classes of analytes in certain diseases [33], and others describing the use of a specific CDA [32,38] or the enantioanalysis of metabolites by liquid chromatography [39].…”