title: Pharmacokinetics and tissue distribution of novel platinum containing anticancer agent BP-C1 studied in rabbits using sector field inductively coupled plasma mass spectrometry.
abstract: A method of platinum quantification in whole blood samples after microwave digestion using sector field inductively coupled plasma mass spectrometry has been developed. The following analytical figures of merit have been established: limit of detection 1.1 µg/L for blood samples, dynamic range 3.6-200 µg/L, intra-day precision (relative standard deviation, n = 9) did not exceed 5%. Spiked samples were analyzed for method validation. The method was used for pharmacokinetics studies of a novel anti-cancer drug BP-С1, a complex of cis-configured platinum and benzene-poly-carboxylic acids. Main pharmacokinetic parameters (area under curve, maximum concentration, clearance, half-life times for α- and β-phase) were estimated for two dosage forms of BP-C1 0.05 and 0.125 mass %. Pharmacokinetic curves were assessed for single and course administration. Studies were performed using rabbits (n = 6) as a model. BP-C1 was injected intramuscularly. The study established dose proportionality of the tested dosage forms and suggested clinical dosing schedule: 5 days of injections followed by 2 days' break. Platinum tissue distribution was studied in tissue samples collected 20 days after the last injection. Predominant platinum accumulation was observed in kidneys, liver, and muscles near injection site. 'Slow' phase of platinum excretion kinetics may be related to the muscles at the injection site.
authors.affiliation: Institute of Toxicology of Federal Medico-Biological Agency, St. Petersburg, Russian Federation.
authors.forename: Denis V
authors.initials: DV
authors.lastname: Navolotskii
authors.affiliation: Institute of Toxicology of Federal Medico-Biological Agency, St. Petersburg, Russian Federation.|Institute of Chemistry, Saint Petersburg State University, St. Petersburg, Russian Federation.
authors.forename: Natalya B
authors.initials: NB
authors.lastname: Ivanenko
authors.affiliation: Institute of Chemistry, Saint Petersburg State University, St. Petersburg, Russian Federation.
authors.forename: Nikolay D
authors.initials: ND
authors.lastname: Solovyev
authors.affiliation: Nobel LTD, St. Petersburg, Russian Federation.|N.N. Petrov Research Institute of Oncology, St. Petersburg, Russian Federation.
authors.forename: Elena I
authors.initials: EI
authors.lastname: Fedoros
authors.affiliation: N.N. Petrov Research Institute of Oncology, St. Petersburg, Russian Federation.
authors.forename: Andrey V
authors.initials: AV
authors.lastname: Panchenko
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000097:blood / Q000493:pharmacokinetics*; D001555:Benzene Derivatives / Q000097:blood / Q000493:pharmacokinetics; D008297:Male; D013058:Mass Spectrometry / Q000379:methods; D009944:Organoplatinum Compounds / Q000097:blood / Q000493:pharmacokinetics*; D011817:Rabbits; D014018:Tissue Distribution
chemical_list: D000970:Antineoplastic Agents; D001555:Benzene Derivatives; D009944:Organoplatinum Compounds
keywords: benzene-poly-carboxylic acids; breast cancer; inductively coupled plasma mass spectrometry; pharmacokinetics; platinum