title: Development and validation of a highly sensitive RIA for zoledronic acid, a new potent heterocyclic bisphosphonate, in human serum, plasma and urine.
abstract: Zoledronic acid is a new, highly potent bisphosphonate drug under clinical evaluation. A radioimmunoassay has been developed to determine zoledronic acid concentration in human serum, plasma, and urine. The assay utilizes rabbit polyclonal antisera against a zoledronic acid-BSA conjugate and a [125I]zoledronic acid derivative as tracer in a competitive format adapted to microtiter plates. The assay shows a LLOQ 0.4 ng/ml in serum or plasma (interassay%CV=17%, accuracy 97%), 5 ng/ml in urine (21%, 98%). In 23 patients receiving 4, 8 or 16 mg of zoledronic acid, drug concentrations in plasma were dose proportional and showed a multiphasic profile, followed by a prolonged gradual decline to concentrations near the LLOQ. Zoledronic acid disposition in plasma and the recovery of only 40-50% of the dose in urine are consistent with the rapid and extensive uptake by and slow release from bone in parallel with renal clearance, typically shown by bisphosphonates.
authors.affiliation: Novartis Pharma Basel, 4002, Basel, Switzerland. francois.legay@pharma.novartis.com
authors.forename: Francois
authors.initials: F
authors.lastname: Legay
authors.forename: Sonia
authors.initials: S
authors.lastname: Gauron
authors.forename: Fabienne
authors.initials: F
authors.lastname: Deckert
authors.forename: Ghislaine
authors.initials: G
authors.lastname: Gosset
authors.forename: Ulrike
authors.initials: U
authors.lastname: Pfaar
authors.forename: Christina
authors.initials: C
authors.lastname: Ravera
authors.forename: Hansjörg
authors.initials: H
authors.lastname: Wiegand
authors.forename: Horst
authors.initials: H
authors.lastname: Schran
mesh_terms: D000328:Adult; D000368:Aged; D019540:Area Under Curve; D011756:Diphosphates / Q000032:analysis / Q000097:blood / Q000737:chemistry / Q000652:urine; D004164:Diphosphonates / Q000032:analysis* / Q000097:blood / Q000737:chemistry* / Q000652:urine; D005260:Female; D006571:Heterocyclic Compounds / Q000032:analysis / Q000097:blood / Q000737:chemistry / Q000652:urine; D006801:Humans; D007093:Imidazoles / Q000032:analysis* / Q000097:blood / Q000737:chemistry* / Q000652:urine; D008297:Male; D008875:Middle Aged; D011863:Radioimmunoassay / Q000379:methods; D015203:Reproducibility of Results; D000077211:Zoledronic Acid
chemical_list: C538827:CGP 58318; D011756:Diphosphates; D004164:Diphosphonates; D006571:Heterocyclic Compounds; D007093:Imidazoles; D000077211:Zoledronic Acid