Liquid chromatography-multistage tandem mass spectrometry for the quantification of dihydroxynonene mercapturic acid (DHN-MA), a urinary end-metabolite of 4-hydroxynonenal

Anal Bioanal Chem. 2005 Apr;381(8):1532-9. doi: 10.1007/s00216-005-3095-6. Epub 2005 Mar 16.

Abstract

The mercapturic acid conjugate of 1,4-dihydroxynonene (DHN-MA) is a urinary metabolite of 4-hydroxynonenal (4-HNE), one of the main lipid peroxidation products occurring in vivo. To determine its level in urine, a combination of liquid chromatography with positive electrospray-multistage tandem mass spectrometry has been developed. A deuterated analog of the target compound (DHN-MA) with six deuterium atoms was synthesized and used as the internal standard. Three-stage tandem mass spectrometry was used, providing good selectivity for the detection of DHN-MA. The response of the system to DHN-MA was linear in the 5-100 ng range. Urine samples spiked with different levels of standard DHN-MA were used to evaluate the influence of matrix effects on the linearity. The repeatability of the method was also determined by using repeated 5 ng injections of DHN-MA, providing a RSD of 10%. The method was then applied to the determination of DHN-MA in rat urine samples; increased levels of urinary DHN-MA in urine from rats treated with BrCCl3 indicates that lipid peroxidation processes take place in such rats.

MeSH terms

  • Acetylcysteine / analogs & derivatives*
  • Acetylcysteine / urine*
  • Aldehydes / metabolism*
  • Animals
  • Chromatography, Liquid / methods*
  • Deuterium
  • Linear Models
  • Male
  • Mass Spectrometry / methods*
  • Rats
  • Rats, Wistar
  • Sensitivity and Specificity

Substances

  • 1,4-dihydroxynonene mercapturic acid
  • Aldehydes
  • Deuterium
  • 4-hydroxy-2-nonenal
  • Acetylcysteine