Development of a nucleotide sugar purification method using a mixed mode column & mass spectrometry detection

J Pharm Biomed Anal. 2015 Nov 10:115:402-9. doi: 10.1016/j.jpba.2015.08.001. Epub 2015 Aug 4.

Abstract

Analysis of nucleotide sugars, nucleoside di- and triphosphates and sugar-phosphates is an essential step in the process of understanding enzymatic pathways. A facile and rapid separation method was developed to analyze these compounds present in an enzymatic reaction mixture utilized to produce nucleotide sugars. The Primesep SB column explored in this study utilizes hydrophobic interactions as well as electrostatic interactions with the phosphoric portion of the nucleotide sugars. Ammonium formate buffer was selected due to its compatibility with mass spectrometry. Negative ion mode mass spectrometry was adopted for detection of the sugar phosphate (fucose-1-phophate), as the compound is not amenable to UV detection. Various mobile phase conditions such as pH, buffer concentration and organic modifier were explored. The semi-preparative separation method was developed to prepare 30mg of the nucleotide sugar. (19)F NMR was utilized to determine purity of the purified fluorinated nucleotide sugar. The collected nucleotide sugar was found to be 99% pure.

Keywords: High performance liquid chromatography; Mass spectrometry; Mixed-mode stationary phase; Nucleotide-sugar; Nucleotides; Sugar phosphate.

MeSH terms

  • Buffers
  • Carbohydrates / analysis*
  • Chromatography, High Pressure Liquid*
  • Fucose / analogs & derivatives
  • Fucose / analysis
  • Hexosephosphates / analysis
  • Hydrogen-Ion Concentration
  • Hydrophobic and Hydrophilic Interactions
  • Magnetic Resonance Spectroscopy
  • Mass Spectrometry*
  • Molecular Structure
  • Nucleoside Diphosphate Sugars / analysis
  • Nucleotides / analysis*
  • Solvents / chemistry
  • Static Electricity
  • Sugar Phosphates / analysis

Substances

  • Buffers
  • Carbohydrates
  • Hexosephosphates
  • Nucleoside Diphosphate Sugars
  • Nucleotides
  • Solvents
  • Sugar Phosphates
  • fucopyranosyl phosphate
  • Fucose