Low concentrations of betaxolol in blood plasma and physiological buffers were determined by selected ion monitoring of the intense m/z 72 fragment [CH2 = NH-CH(CH3)2]+ formed by electron impact ionization of the O-trimethylsilyl derivative. At a mass spectrometric resolution of 3000, fewer potentially interfering peaks were seen than at low resolution. There remained a chemical interference, corresponding to 100 pg/sample, which arose during treatment of the samples. This method is more sensitive than previous ones, but it is restricted to situations where the specificity can be controlled. When the m/z 72 fragment was mass-shifted by using betaxolol appropriately labelled with deuterium or 13C, both the interference and the baseline noise were greatly reduced; concentrations of labelled betaxolol as low as 10-20 pg/sample can be determined with little difficulty.