Application of inductively coupled plasma mass spectrometry and high-performance liquid chromatography--with parallel electrospray mass spectrometry to the investigation of the disposition and metabolic fate of 2-, 3- and 4-iodobenzoic acids in the rat.
ICP-MS, HPLC-ICP-MS and HPLC-ICP-MS/ESI-MS have been applied to determine the disposition and metabolic fate of 2-, 3- and 4-iodobenzoic acids following intraperitoneal administration at 50 mg kg(-1) to male bile duct cannulated rats. Quantitative excretion balance studies based on the determination of the total iodine content of urine and bile showed that all three iodobenzoic acids were rapidly excreted. Recoveries ranging from 95 to 105% of the administered doses were achieved within 24 h of administration. Metabolite profiles for urine and bile showed extensive metabolism with unchanged iodobenzoic acids forming a minor part of the total. A combination of alkaline hydrolysis and MS enabled the identification of the major metabolites of all three iodobenzoic acids as glycine and ester glucuronide conjugates with very little if any of the parent compounds excreted unchanged.
Department of Drug Metabolism and Pharmacokinetics, AstraZeneca, Mereside, Alderley Park, Macclesfield, Cheshire, SK10 4TG, UK. dpj@dfuni.dk
Berit Packert
BP
Jensen
Christopher J
CJ
Smith
Christopher
C
Bailey
Colin
C
Rodgers
Ian D
ID
Wilson
Jeremy K
JK
Nicholson
D000818:Animals; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D007463:Iodobenzoates / Q000378:metabolism* / Q000493:pharmacokinetics; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*
D007463:Iodobenzoates