Measurement of free and total sialic acid by isotopic dilution liquid chromatography tandem mass spectrometry method

J Chromatogr B Analyt Technol Biomed Life Sci. 2011 Dec 1;879(31):3694-9. doi: 10.1016/j.jchromb.2011.10.009. Epub 2011 Oct 13.

Abstract

The measurement of urine sialic acid (N Acetylneuraminic Acid: Neu5Ac) is useful for screening sialic acid storage disorders. We developed a new LC MS/MS method for the determination of a sialic acid. Urine samples were analyzed, after an HCl n-Butanol derivatization step, by a reverse phase based high-performance liquid chromatography method using 1,2,3-(13)C(3) N-Acetyl-D-neuraminic Acid ((13)C-Neu5Ac) as an internal standard. Selective detection was performed by tandem mass spectrometry using an electrospray source operating in positive ionization mode employing multiple reactions monitoring to monitor N-Acetylneuraminic Acid and the internal standard. The transitions m/z 366→330 and 369→333 for Neu5Ac and (13)C-Neu5Ac were respectively monitored. The limit of the method quantification was 1.40 μM of N-Acetylneuraminic Acid and the calibration curve showed a good linearity up to 1000 μM. The within assay precision and accuracy of the method ranged from 3.22 to 5.95% and 98.69 to 109.18%, respectively and the between assay precision and accuracy ranged, respectively, from 5.15 to 7.65% and 96.14 to 102.30%. The method can be applied for the determination of N-Acetylneuraminic Acid concentrations in urine and other biological fluids (e.g., amniotic and peritoneal fluids).

MeSH terms

  • Carbon Isotopes
  • Chromatography, High Pressure Liquid
  • Chromatography, Reverse-Phase / methods*
  • Creatinine / urine
  • Drug Stability
  • Humans
  • Least-Squares Analysis
  • N-Acetylneuraminic Acid / chemistry
  • N-Acetylneuraminic Acid / urine*
  • Reproducibility of Results
  • Sensitivity and Specificity
  • Sialic Acid Storage Disease / urine
  • Tandem Mass Spectrometry / methods*

Substances

  • Carbon Isotopes
  • Creatinine
  • N-Acetylneuraminic Acid