Characterization of glucuronic acid conjugates of a novel angiotensin receptor antagonist.
Nanogram quantities of glucuronic acid conjugates of GR117289 in rat and dog bile have been analysed by semi-microbore high-performance liquid chromatography (HPLC)/ionspray mass spectrometry with on-line UV diode array detection. The determination of drug metabolites in bile has often proved problematical due to the large number of endogenous components in this biological matrix, in particular the bile acids. Semi-microbore HPLC is useful for concentrating small quantities of material and, in combination with an on-line diode array detector, for distinguishing between drug related and endogenous components. A novel angiotensin II receptor antagonist, GR117289, had proved difficult to analyse by thermospray mass spectrometry because of its thermal lability. The use of the less thermally dependent technique of ionspray mass spectrometry allowed the characterization of nanogram quantities of glucuronic acid metabolites of GR117289 in bile.
Bowers
G D
GD
Drug Metabolism Division, Glaxo Group Research Limited, Ware, Hertfordshire, UK.
Eddershaw
P J
PJ
Hughes
S Y
SY
Manchee
G R
GR
Oxford
J
J
D057911:Angiotensin Receptor Antagonists; D000818:Animals; D001646:Bile / Q000737:chemistry / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D004285:Dogs; D005965:Glucuronates / Q000032:analysis*; D007202:Indicators and Reagents; D007275:Injections, Intravenous; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D013058:Mass Spectrometry; D009539:Nicotinic Acids / Q000032:analysis* / Q000737:chemistry / Q000493:pharmacokinetics; D051381:Rats; D013056:Spectrophotometry, Ultraviolet; D013777:Tetrazoles / Q000032:analysis* / Q000737:chemistry / Q000493:pharmacokinetics
D057911:Angiotensin Receptor Antagonists; D005965:Glucuronates; D007202:Indicators and Reagents; D009539:Nicotinic Acids; D013777:Tetrazoles; C078790:GR 117289