4-(4,6-Dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium Chloride as an Enantioseparation Enhancer for Chiral Derivatization-LC Analysis of D- and L-Amino acids

Abstract

We have developed a high-resolution chiral derivatization-LC method for the determination of D-and L-amino acids using 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride (DMT-MM) as an enantioseparation enhancer. In this method, D-and L-amino acids were derivatized with (S)-(-)-1-(naphthyl)ethylamine (NEA) in the presence of DMT-MM as a condensing agent. These conditions resulted in the amino group of the D-and L-amino acid-NEA derivative being introduced in the triazine unit of DMT-MM, producing sterically bulky diastereoisomers. The resulting derivatives of the D-and L-amino acids could be discriminated and successfully enantioseparated through reversed-phase LC. This enantioseparation enhancement effect was demonstrated when using six other commercially available chiral amines as derivatization reagents. Since triazine modification possesses high ESI-responsivity, they showed higher sensitivities than non-triazine derivatives. The developed derivatization method was successfully applied to highly sensitive quantification of D-and L-amino acids by combining LC-MS/MS analysis.

Metabolic Profiling of Urinary Chiral Amino-Containing Biomarkers for Gastric Cancer Using a Sensitive Chiral Chlorine-Labeled Probe by HPLC-MS/MS

“…The LOQ ranged from 0.0025 to 0.5 μM. All the LOD data in this work are lower than those of the previous d -BPBr-based work which may arise from good reaction and detection performance of the chlorine-containing derivatization reagent, − the optimized C18 HPLC separation procedure, and the more favorable isotope abundance ratio of Cl (3:1) than Br (1:1) for quantitation. Therefore, our method, to a greater extent, improves the detection of trace d -amino acids in biological samples.…”

“…Compared with 15 N- and 13 C-coded labeling reagents, the cost of d -BPBr synthesis is inexpensive and the materials for d -BPBr synthesis are easily available . Since Cl has been widely used in the structure of derivatization reagents for amine with good reaction and detection performance, − we designed and synthesized chlorine-labeled probes d -BPCl and L-BPCl for the analysis of amino-containing compounds based on BPBr. Compared with d -BPBr, d -BPCl showed better sensitivity and higher chiral selectivity (Cs, defined as the peak area ratio of d - to l -amino acids labeled with d -BPCl) for all the targeted amino acid enantiomers.…”

Voltammetric Determination of Amino Acids Based on the Measurement of Reduction Prepeak of Quinone Caused by Surplus Acid after Neutralization

“…Amino acid analysis is an important technique in many pharmaceutical, medical, chemical, food research, and industrial areas [1][2][3]. Thus far, various analytical methods have been proposed to determine amino acids, including high-performance liquid chromatography, capillary electrophoresis, enzyme assay, and chemical sensors [4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21]. Usually, because of the weak light-absorptive property of amino acids, pre-or post-column derivatization with an appropriate labeling reagent is performed for determining amino acids with sensitivity and selectivity in HPLC with UV detection (HPLC-UV) and fluorescence detection (HPLC-FL) systems [9,10].…”

“…Usually, because of the weak light-absorptive property of amino acids, pre-or post-column derivatization with an appropriate labeling reagent is performed for determining amino acids with sensitivity and selectivity in HPLC with UV detection (HPLC-UV) and fluorescence detection (HPLC-FL) systems [9,10]. Recently, many LC with mass spectrometric detection methods such as LC-MS/MS and LC-qTOF-MS/MS have been proposed [11][12][13], and these methods are applied to the carrying out of metabolism studies and diagnosis based on amino acids profiles [13][14][15][16]. Electrochemical detection generally has the following merits: an electrochemical detector is inexpensive compared with a spectrometric detector, electrochemical devices, including electrodes, can be easily minimalized to develop a portable sensor with simple procedures, and a low energy requirement that can be used either in laboratory or for on-site measurements [22].…”