Pharmacokinetics of oral timolol studied by mass fragmentography

The pharmacokinetics of timolol, after oral administration of single 20 mg doses to healthy subjects, has been studied using an original electron beam ionization GLC-mass spectrometry technique with computer -- controlled multiple ion detection. This method of mass fragmentography, tested with propranolol as an internal standard, permitted the measurement of timolol concentrations as low as 1 ng/ml with good precision and accuracy. It enabled the plasma level to be followed up to the twelfth hour after treatment. Individual variation was observed in bioavailability; the peaks plasma concentration (Cmax) of 50 to 103 ng/ml being achieved at different times(0.5--3h). The residual level after 12 h differed greatly between the subjects (0.8 to 7.2 ng/ml). The mean half-life of the terminal elimination phase was 2.62 +/- 0.17 h. Extra-renal elimination (metabolic and biliary) represented the main route of elimination, with a renal to body clearance ratio of 0.123. This level paralleled the percentage of unaltered timolol excreted in urine 24 h after its administration.