title: Improved high-performance liquid chromatographic method for the pharmacokinetic studies of a novel iron chelator, CP502, in rats.
abstract: An improved reverse-phase high-performance liquid chromatographic method (RP-HPLC) for the determination of a novel iron chelator CP502 (1,6-dimethyl-3-hydroxy-4-(1H)-pyridinone-2-carboxy-(N-methyl)-amide hydrochloride) in rat plasma, urine and feces was developed and validated. The separation was performed on a polymeric column using a mobile phase composed of 1mM ethylenediaminetetra-acetic acid disodium salt (EDTA), acetonitrile, methanol and methylene chloride. Separation of CP502 from plasma, urine or feces endogenous compounds was achieved by gradient elution. Retention times of CP502 and its major metabolite (glucuronide) were about 13 and 4 min, respectively. The method was validated in terms of limit of detection (LOD), limit of quantification (LOQ), selectivity (endogenous from plasma, urine or feces), linearity, extraction recovery, robustness (column selection, mobile phase composition, detection mode, internal standard (IS) selection, analyte stability), day-to-day reproducibility and system suitability (repeatability, peak symmetry and resolution). The method is applicable to bioavailability and pharmacokinetic studies of CP502 in rats.
authors.affiliation: Leslie Dan Faculty of Pharmacy, University of Toronto, 19 Russell Street, Toronto, Ont., Canada M5S 2S2.
authors.forename: Jasmina
authors.initials: J
authors.lastname: Novakovic
authors.forename: Angelo
authors.initials: A
authors.lastname: Tesoro
authors.forename: Michael
authors.initials: M
authors.lastname: Spino
authors.forename: Jake
authors.initials: J
authors.lastname: Thiessen
mesh_terms: D000818:Animals; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D007502:Iron Chelating Agents / Q000493:pharmacokinetics*; D008297:Male; D011728:Pyridones / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012015:Reference Standards; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
chemical_list: C487538:1,6-dimethyl-3-hydroxy-4-(1H)-pyridinone-2-carboxy-(N-methyl)-amide hydrochloride; D007502:Iron Chelating Agents; D011728:Pyridones