Metabolism of benzothiazole. I. Identification of ring-cleavage products.

1. The metabolic fate of benzothiazole in guinea pig has been investigated following i.p. administration at a dose of 30 mg/kg. 2. Five ring-cleavage products were identified in urinary extracts by g.l.c.-mass spectra. By reference to authentic compounds the three major metabolites were shown to be 2-methylmercaptoaniline (I), 2-methylsulphinylaniline (II) and 2-methylsulphonylaniline (III). On the basis of the mass spectrometric evidence the remaining two metabolites were postulated to be 2-methylsulphinylphenylhydroxylamine (IV) and 2-methylsulphonylphenylhydroxylamine (V). 3. I, II and III were present in conjugated and unconjugated forms; IV and V were identified only after hydrolysis with sulphatase.

Unequivocal synthesis and characterisation of dopamine 3- and 4-O-sulphates.

The major metabolic products of the endogeneous catecholamine dopamine are its 3- and 4-O-sulphates which have also been implicated as intermediates in noradrenaline biosynthesis. Because of the unsatisfactory status of the literature concerning the synthesis, isolation, purity and characterisation of the dopamine O-sulphates we describe both a one-step synthesis and definitive separation and characterisation procedures for these metabolites. High-performance liquid chromatography (HPLC) combined with high-field nuclear magnetic resonance techniques were employed. The chemical sulphonation of dopamine gave three synthetic products, whose relative amounts depended critically upon the reaction conditions employed. Dopamine 3- and 4-O-sulphates together with dopamine 6-sulphonic acid, a hitherto undescribed derivative of dopamine, were for the first time isolated and characterised unequivocally. It should now prove possible to reappraise critically the biological significance of the major metabolite products of dopamine.