CHARACTERIZATION OF GLUCURONIC-ACID CONJUGATES OF A NOVEL ANGIOTENSINRECEPTOR ANTAGONIST

Nanogram quantities of glucuronic acid conjugates of GR117289 in rat a nd dog bile have been analysed by semi-microbore high-performance liqu id chromatography (HPLC)/ionspray mass spectrometry with on-line UV di ode array detection. The determination of drug metabolites in bile has often proved problematical due to the large number of endogenous comp onents in this biological matrix, in particular the bile acids. Semi-m icrobore HPLC is useful for concentrating small quantities of material and, in combination with an on-line diode array detector, for disting uishing between drug related and endogenous components. A novel angiot ensin II receptor antagonist, GR117289, had proved difficult to analys e by thermospray mass spectrometry because of its thermal lability. Th e use of the less thermally dependent technique of ionspray mass spect rometry allowed the characterization of nanogram quantities of glucuro nic acid metabolites of GR117289 in bile.