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In this study an analytical procedure for the fl-sympathomimetics is presented by which the low therapeutic concentrations in biological material can be measured using the unlabelled drug. The developed assay is applied to terbutaline (Bricanyl| one of the modern fl2-adrenergics which is widely prescribed in The Netherlands. Its pharmacokinetics and -dynamics upon different modes of administration are studied as well as its clinical toxicological aspects.In the first chapter a general introduction to the sympathomimetics is presented. The development of the modern fl-adrenergic compounds is discussed in terms of fl-specificity and metabolism. The literature comparing the ill-and fl2-effect in in vitro studies is reviewed. Furthermore a tabular review of clinical studies relating the effects on the lung function following oral, subcutaneous and aerosol administration of a variety of fl2-sympathomimetics is given. The occurrence 0f tremor and side effects on the heart are briefly indicated.Chapter 2 describes an analytical profile of terbutaline, special attention is paid to the development of an accurate and sensitive detection procedure. From the different approaches discussed, the method employing a chemical ionisation technique with subsequent mass fragmentography proved to be sufficiently sensitive to cope with the therapeutic terbutaline levels expected in biological material. The developed assay uses a stable isotope derivative of terbutaline as internal standard and provides quantitation on 4 ions to assure high specificity. The decomposition in aqueous solutions under different storage conditions is discussed.Problems concerning the extraction from aqueous solutions, biological fluids and tissues are discussed. An overview of the ion pair extraction shows that after comprehensive modification this technique can be adapted for the determination of terbutaline at concentrations in the pg/ml to ng/ml range. A theoretical approach shows that only the ion pair of terbutaline and bis(2-ethylhexyl) phosphoric acid is extracted without the formation of higher associates. Modifications required for optimum extraction of a variety of other fl-sympathomimetics are also discussed. Measurements in biological material show recovery of 80% in blood and 60% in tissues and indicate that only the free terbutaline is extracted.Chapter 4 deals with the clinical pharmacokinetics of terbutaline. A simple approach of the theory is discussed and allows an easy calculation of the necessary kinetic parameters on a small micro computer. Serum levels obtained after infusion, subcutaneous injection and oral administration to volunteers and patients are compared. Upon oral administration of a 5 mg Bricanyl | tablet the bioavailability is measured in relation to subcutaneous administration of

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