The characterisation of the major metabolite of salmeterol in the dog

J Pharm Biomed Anal. 1998 Nov;18(3):461-70. doi: 10.1016/s0731-7085(98)00114-9.

Abstract

Salmeterol xinafoate is the first of a new class of long acting, selective beta2-adrenoceptor agonists introduced for the treatment of asthma. The major metabolite of salmeterol in the dog has been identified as the 3-catechol sulphate of the benzoic acid derivative. This metabolite was isolated from dog bile and was shown to have very similar physiochemical properties to a major endogenous component of bile, the bile acids, creating a complex analytical challenge. Initial experiments, involving hydrolysis with the enzyme sulphatase, suggested that the metabolite was a sulphate conjugate. However, complete identification of the metabolite was complicated in part due to the loss, by metabolism, of deuterium atoms added to the compound, specifically as a marker for mass spectrometry. Subsequently, a synthesis of salmeterol was completed with deuterium labels in different positions. This material was used as a substrate for dog liver slices, a simpler matrix than dog bile, which provided the basis for the metabolite's identification. The metabolite was characterised by the use of spectroscopic techniques, in particular LC/MS, LC/MS/MS and NMR.

MeSH terms

  • Albuterol / analogs & derivatives*
  • Albuterol / analysis
  • Albuterol / metabolism
  • Animals
  • Bile / chemistry*
  • Dogs
  • Gas Chromatography-Mass Spectrometry
  • In Vitro Techniques
  • Liver / metabolism*
  • Magnetic Resonance Spectroscopy
  • Male
  • Salmeterol Xinafoate
  • Sulfates / metabolism*

Substances

  • Sulfates
  • Salmeterol Xinafoate
  • Albuterol