Selected ion monitoring of metoprolol and two metabolites in plasma and urine using deuterated internal standards

A highly sensitive and specific quantitative assay for metoprolol and two of its metabolites, containing an unchanged 2‐hydroxy‐4‐isopropylaminopropoxy sidechain, has been developed. The compounds are isolated from the alkalized sample (plasma or urine) by extraction with dichloromethane, and converted to trifluoroacetyl derivatives by reaction with methyl‐bis‐(trifluoroacetamide). The reaction mixture is gas chromatographed on an OV‐17 column and each substance is assayed by electron impact mass spectrometry using selected ion monitoring, and quantified by comparing the intensity of fragment ion m/z 266 with the intensities of corresponding fragment ions from the deuterated internal standards (m/z 270 and 271). It is possible to determine concentrations as low as 1 nmol I−1 (0.3 ng ml−1) in 1 ml of sample with a relative standard deviation of less than 10%.