Identification of sulfation sites of metabolites and prediction of the compounds' biological effects

Anal Bioanal Chem. 2006 Oct;386(3):666-74. doi: 10.1007/s00216-006-0495-1. Epub 2006 May 25.


Characterizing the biological effects of metabolic transformations (or biotransformation) is one of the key steps in developing safe and effective pharmaceuticals. Sulfate conjugation, one of the major phase II biotransformations, is the focus of this study. While this biotransformation typically facilitates excretion of metabolites by making the compounds more water soluble, sulfation may also lead to bioactivation, producing carcinogenic products. The end result, excretion or bioactivation, depends on the structural features of the sulfation sites, so obtaining the structure of the sulfated metabolites is critically important. We describe herein a very simple, high-throughput procedure for using mass spectrometry to identify the structure-and thus the biological fate-of sulfated metabolites. We have chemically synthesized and analyzed libraries of compounds representing all the biologically relevant types of sulfation products, and using the mass spectral data, the structural features present in these analytes can be reliably determined, with a 97% success rate. This work represents the first example of a high-throughput analysis that can identify the structure of sulfated metabolites and predict their biological effects.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alcohols / chemistry
  • Alcohols / metabolism
  • Chemistry, Pharmaceutical / methods*
  • Hydroxylamines / chemistry
  • Hydroxylamines / metabolism
  • Metabolic Detoxication, Phase II
  • Molecular Structure
  • Pharmaceutical Preparations / metabolism*
  • Spectrometry, Mass, Secondary Ion
  • Structure-Activity Relationship
  • Sulfates / analysis
  • Sulfates / chemistry*
  • Sulfates / metabolism*


  • Alcohols
  • Hydroxylamines
  • Pharmaceutical Preparations
  • Sulfates