Efficient and selective analytical method for the quantification of a β-adrenoceptor agonist, isoproterenol, by LC-MS/MS and its application to pharmacokinetics studies

Isoproterenol (ISO) is a synthetic catecholamine with a powerful cardiac stimulate, bronchial smooth and skeletal muscle relaxation, coronary artery and peripheral vasodilator effects. In this study, a simple, rapid, and selective liquid chromatography-tandem mass spectrometry has been developed for the determination of ISO in rat plasma. Proteins were precipitated in plasma samples with 0.1gmL(-1) trichloroacetic acid and the ISO/internal standard (IS) were separated on a C-8 column. The ISO was detected by a triple-quadrupole mass spectrometer with electrospray ionization source. The transitions of m/z 212.1193.9 for ISO and m/z 285.2193.2 for IS were conducted through multiple reaction monitoring mode. This method was linear over the range of 2-500ngmL(-1). The intra- and inter-day assay precision were observed between 3 and 10%. The accuracy was within +/- 11%. Stability study results demonstrated that ISO was stable in the autosampler at 4 degrees C for 24hr, and for 8hr at room temperature. Only one freeze-thaw cycle at -80 degrees C for 24hr was found to be stable. The validated method was successfully applied to a pharmacokinetic study of ISO in rats following subcutaneous administration.