The characterisation of the major metabolite of salmeterol in the dog.

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.

journal_name

J Pharm Biomed Anal

authors

Bowers GD,Bayliss MK,Donnelly MC,Fellows I,Ismail IM,Mookherjee CR

doi

10.1016/s0731-7085(98)00114-9

subject

Has Abstract

pub_date

1998-11-01 00:00:00

pages

461-70

issue

3

eissn

0731-7085

issn

1873-264X

pii

S0731-7085(98)00114-9

journal_volume

18

pub_type

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