Investigation of the metabolic fate of 2-, 3- and 4-bromobenzoic acids in bile-duct-cannulated rats by inductively coupled plasma mass spectrometry and high-performance liquid chromatography/inductively coupled plasma mass spectrometry/electrospray mass spectrometry.
Inductively coupled plasma mass spectrometry (ICPMS) has been used to determine the rate and routes of excretion of bromine following the intraperitoneal administration (50 mg kg(-1)) of 2-, 3- and 4-bromobenzoic acids to male bile-duct-cannulated rats. Analysis of urine and bile for (79/81)Br using ICPMS showed that all three bromobenzoic acids were rapidly excreted (82-98%) within 48 h of dosing, primarily via the urine. High-performance liquid chromatography/inductively coupled plasma mass spectrometry (HPLC/ICPMS) was then used to obtain metabolite profiles for bile and urine. These profiles revealed that extensive metabolism had taken place, with the unchanged bromobenzoic acids forming a minor part of the total of compound-related material detected. Concomitant MS studies, supplemented by alkaline hydrolysis, enabled the identification of the major metabolite of all three of the bromobenzoic acids as a glycine conjugate. Ester glucuronide conjugates were also identified, but formed only a small proportion of total.
Jensen
Berit Packert
BP
Department of Analytical Chemistry, The Danish University of Pharmaceutical Sciences, Universitetsparken 2, DK-2100 Copenhagen Ø, Denmark. bpj@dfuni.dk
Smith
Christopher J
CJ
Bailey
Christopher J
CJ
Rodgers
Colin
C
Wilson
Ian D
ID
Nicholson
Jeremy K
JK
D000818:Animals; D001646:Bile / Q000737:chemistry / Q000378:metabolism; D001652:Bile Ducts / Q000601:surgery; D001970:Bromobenzoates / Q000008:administration & dosage / Q000493:pharmacokinetics*; D002404:Catheterization; D002851:Chromatography, High Pressure Liquid; D007274:Injections, Intraperitoneal; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*; D016482:Urinalysis
D001970:Bromobenzoates