title: Determination of the platinum drug cis-amminedichloro(2-methylpyridine)platinum(II) in human urine by liquid chromatography-tandem mass spectrometry.
abstract: A validated stable isotope dilution liquid chromatography-tandem mass spectrometry assay for the novel platinum drug cis-amminedichloro(2-methylpyridine)platinum(II) (ZD0473) in human urine has been developed. This method uses selected reaction monitoring on the transition of m/z 393 [M+NH(4)](+) to m/z 304 [M+NH(4)-NH(3)-2 x H(35)Cl](+) for ZD0473, and m/z 400 [M+NH(4)](+) to m/z 310 [M+NH(4)-NH(3)-H(35)Cl-(2)H(35)Cl](+) for the internal standard [(2)H(7)]ZD0473. Standard curves were prepared over the range from 0.15 to 50 microg/ml. The lower limit of quantitation was 0.2 microg/ml for 100 microl of urine. This simple, rapid, reliable, and sensitive method of quantitation displayed acceptable accuracy and precision over the 3 days of assay validation. A novel platinum adduct was formed during the storage of ZD0473 in human urine. The adduct did not correspond to any of the typical sulfhydryl adducts that have been identified previously for platinum drugs. Formation of the adduct was prevented by the addition of 50% (w/v) sodium chloride to the urine. The assay can be used to quantify intact ZD0473 in the urine of subjects dosed with this new platinum drug.
authors.affiliation: Center for Cancer Pharmacology, Department of Pharmacology, University of Pennsylvania, 1254 BRB II/III, 421 Curie Boulevard, Philadelphia, PA 19104-6160, USA.
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Oe
authors.forename: Ye
authors.initials: Y
authors.lastname: Tian
authors.forename: Peter J
authors.initials: PJ
authors.lastname: O'Dwyer
authors.forename: David W
authors.initials: DW
authors.lastname: Roberts
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Bailey
authors.forename: Ian A
authors.initials: IA
authors.lastname: Blair
mesh_terms: D002138:Calibration; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D006801:Humans; D009944:Organoplatinum Compounds / Q000652:urine*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*
chemical_list: D009944:Organoplatinum Compounds; C110525:amminedichloro(2-methylpyridine)platinum(II)