title: An enzyme inhibition assay for the quantitative determination of the new bisphosphonate zoledronate in plasma.
abstract: Zoledronate, 2-(imidazole-1-yl)-1-hydroxyethane-1,1-bisphosphonic acid is a new 3rd generation bisphosphonate. A specific enzyme inhibition assay was developed for the determination of zoledronate in plasma of animals and man. The multistep synthesis of cholesterol and some of its precursors (lanosterol, squalene) from 14C-labeled mevalonic acid lactone is catalyzed by the S12 fraction of homogenized rat liver in the presence of ATP, NADH and Mg2+. After hydrolysis of the reaction mixture with KOH, lipophilic reaction products were extracted with hexane and the overall yield determined by radiometry. Addition of zoledronate inhibited the formation of cholesterol and its precursors in a dose dependent manner. The described method is suitable to specifically and quantitatively measure concentrations of zoledronate down to 25 ng ml-1 in human and animal (dog, rat) plasma with acceptable reproducibility and accuracy.
authors.affiliation: Research and Development Department, Ciba-Geigy Limited, Basel, Switzerland.
authors.forename: F
authors.initials: F
authors.lastname: Risser
authors.forename: C U
authors.initials: CU
authors.lastname: Pfister
authors.forename: P H
authors.initials: PH
authors.lastname: Degen
mesh_terms: D000818:Animals; D004164:Diphosphonates / Q000097:blood*; D004285:Dogs; D004791:Enzyme Inhibitors; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000097:blood*; D008099:Liver / Q000378:metabolism*; D008297:Male; D051381:Rats; D015203:Reproducibility of Results; D013261:Sterols / Q000096:biosynthesis*; D000077211:Zoledronic Acid
chemical_list: D004164:Diphosphonates; D004791:Enzyme Inhibitors; D007093:Imidazoles; D013261:Sterols; D000077211:Zoledronic Acid