Metabolite profiling study of propranolol in rat using LC/MS/MS analysis

Abstract

Metabolite profiling is one of the most challenging fields in applied mass spectrometry. Mass spectrometry was used to characterize the metabolites of propranolol, a β‐adrenergic receptor antagonist containing numerous oxidation sites. Propranolol is extensively metabolized, with most metabolites appearing in urine. Urine samples were collected from young adult male Sprague–Dawley rats. Structural identification of various metabolites was performed by LC/MS/MS, using a PE SCIEX triple quadrupole instrument (PE SCIEX API 3000). Metabolites were itemized using several LC/MS/MS techniques, including Q3 full scan and precursor and constant neutral loss experiments. A looped experiment technique revealed the presence of mono‐ and di‐hydroxylated metabolites as well as regio isomers of hydroxy‐ and dihydroxy‐propranolol glucuronides and propranolol glucuronic acid. Propranolol glucuronide was not observed, while the presence of dealkylated metabolites was suggested but not confirmed. Copyright © 1999 John Wiley & Sons, Ltd.

Liquid chromatography-mass spectrometry in the study of the metabolism of drugs and other xenobiotics

“…This mode is specially suited to samples where more than one metabolite sharing the same metabolic pathway is expected. Examples reviewed in this paper include for example the use of CNL scanning to detect glucuronides of propranolol (a b-blocker) by monitoring the loss of 176 amu (glucuronyl moiety) (Beaudry et al, 1999) and the detection of DNA adducts of heterocyclic aromatic amines (Gangl et al, 1999).…”

Metabolomics — the link between genotypes and phenotypes

“…A typical example is the elucidation of the biochemical pathways of propanolol degradation in rats by LC/MS/MS (Beaudry et al, 1999). In other applications, a combination of different techniques is used such as profiling the degradation of linoleic acid in stored apples by GC/MS, LC/MS/MS and LC coupled to radioactivity detection (Beuerle and Schwab, 1999).…”

The characterisation of selected drugs with amine-containing side chains using electrospray ionisation and ion trap mass spectrometry and their determination by HPLC–ESI-MS

“…Beaudry et al [14] have used this latter signal to identify metabolites of propranolol in which the amine-containing side chain is not modified (e.g. hydroxylated ring and glucuronide metabolites) by performing a precursor ion scan of m/z 116.…”