Simultaneous measurement of amino acid enantiomers in the serum of late-life depression patients using convenient LC-MS/MS method with Nα-(5-fluoro-2,4-dinitrophenyl)-l-leucinamide Derivatization

J Pharm Biomed Anal. 2023 Jun 15:230:115387. doi: 10.1016/j.jpba.2023.115387. Epub 2023 Apr 5.

Abstract

D-amino acids may be indicators of late-life depression but separation and quantification of enantiomers which differ only by optical rotation sign remain challenging due to their identical physical and chemical properties. A convenient LC-MS/MS method was developed for the simultaneous measurement of l- and d-amino acids based on the chiral derivatization reagent, Nα-(5-fluoro-2,4-dinitrophenyl)-L-leucinamide, and conventional octadecylsilane reversed-phase column. Methanol was used as the extraction solvent and a single-step derivatization reaction using volatile triethylamine eliminated the requirement for desalination prior to LC-MS/MS. Simultaneous separation and identification of 21 amino acids and the enantiomeric compositions of the 18 chiral proteogenic entities were achieved. Low limits of detection (0.03-4.0 nM), wide linear range (0.01-20 μM), good precision (RSDs < 10 %) and negligible matrix effects indicated the suitability of the method. Application of the method to the quantification of serum chiral amino acids in late-life depression patients (n = 40) and controls (n = 35) found a total of 17 L-amino acids, 14 D-amino acids, DL-asparagine, glycine and γ-aminobutyric acid. The statistical evaluation showed significant differences of glycine, L-threonine and D-methionine between late-life depression patients and controls, indicating that these are potential biomarkers of late-life depression.

Keywords: Amino acid enantiomers; LC-MS/MS; Late-life depression; N(α)-(5-fluoro-2,4-dinitrophenyl)-L-leucinamide.

MeSH terms

  • Amino Acids* / chemistry
  • Chromatography, High Pressure Liquid / methods
  • Chromatography, Liquid / methods
  • Depression*
  • Dinitrobenzenes
  • Glycine
  • Humans
  • Stereoisomerism
  • Tandem Mass Spectrometry / methods

Substances

  • Amino Acids
  • leucinamide
  • Glycine
  • Dinitrobenzenes