Quantitative analysis of propranolol and metabolites by a gas chromatograph mass spectrometer computer technique

Abstract

A quantitative assay for urinary propranolol and six of its unconjugated metabolites by a gas chromatography mass spectrometry computer system has been developed. Conjugated metabolites are also determined following enzyme hydrolysis. These compounds are separated from urine by Amberlite XAD-2 resin column chromatography and are converted to methyl esters and trifuoroacetyl derivatives. Each substance is quantitated from reconstructed ion chromatograms using a specific mass or sum of masses for each compound by comparing its area with that of an appropriate internal standard. The minimum detectable concentrations are in the range of 50–100 ng ml−1. The calibrations are linear from 0.10–15.0 μg ml−1 with recoveries ranging from 62–91%. This procedure yields a high degree of specificity, selectivity and reproducibility, as demonstrated by the analyses of urine from dogs receiving single 40 mg doses of propranolol orally.