Optimized one-pot derivatization and enantioseparation of cysteine: Application to the study of a dietary supplement

J Pharm Biomed Anal. 2020 Feb 20:180:113066. doi: 10.1016/j.jpba.2019.113066. Epub 2019 Dec 23.

Abstract

Cysteine is a sulfur-containing amino acid which plays an outstanding role in many biological pathways in mammals. The analysis and quantification of native cysteine remains a critical issue due to its highly reactive thiol group evolving to the disulfide cystine derivative through oxidation reaction. Aimed at improving the derivative stability, cysteine was labelled with 4-fluoro-7-nitro-2,1,3-benzoxadiazole (NBD-F), which reacts with both amino and thiol groups. The derivatization was optimized and the chemical identity of the reaction product was assessed via high-resolution mass spectrometry. The NBD-cysteine derivative resulted stable for 10 days. This derivative was enantioresolved (α and RS equal to 1.25 and 2.70, respectively) thanks to a (R,R)-Whelk-O1 phase with the following chromatographic setting: eluent, MeOH/water-90/10 (v/v) with 15 mM ammonium formate (pwsH 6.0); column temperature, 35 °C; flow rate, 1.0 mL/min. The developed method was validated following the ICH guidelines and applied for the quality control of a L-cysteine containing dietary supplement.

Keywords: Cysteine derivative; Dietary supplement; Enantioselective liquid chromatography; Method validation; Optimized derivatization process.

MeSH terms

  • Capsules
  • Chromatography, High Pressure Liquid / methods*
  • Cysteine / analysis*
  • Cysteine / chemistry
  • Cysteine / standards*
  • Dietary Supplements / analysis*
  • Dietary Supplements / standards*
  • Drug Stability
  • Limit of Detection
  • Mass Spectrometry / methods*
  • Reproducibility of Results
  • Stereoisomerism

Substances

  • Capsules
  • Cysteine