title: Development and Validation of an Inductively Coupled Plasma Mass Spectrometry (ICP-MS) Method for Quantitative Analysis of Platinum in Plasma, Urine, and Tissues.
abstract: Cisplatin, a platinum chemotherapeutic, is one of the most commonly used chemotherapeutic agents for many solid tumors. In this work, we developed and validated an inductively coupled plasma mass spectrometry (ICP-MS) method for quantitative determination of platinum levels in rat urine, plasma, and tissue matrices including liver, brain, lungs, kidney, muscle, heart, spleen, bladder, and lymph nodes. The tissues were processed using a microwave accelerated reaction system (MARS) system prior to analysis on an Agilent 7500 ICP-MS. According to the Food and Drug Administration guidance for industry, bioanalytical validation parameters of the method, such as selectivity, accuracy, precision, recovery, and stability were evaluated in rat biological samples. Our data suggested that the method was selective for platinum without interferences caused by other presenting elements, and the lower limit of quantification was 0.5 ppb. The accuracy and precision of the method were within 15% variation and the recoveries of platinum for all tissue matrices examined were determined to be 85-115% of the theoretical values. The stability of the platinum-containing solutions, including calibration standards, stock solutions, and processed samples in rat biological matrices was investigated. Results indicated that the samples were stable after three cycles of freeze-thaw and for up to three months.
authors.affiliation: HylaPharm LLC, Lawrence, USA.
authors.forename: Ti
authors.initials: T
authors.lastname: Zhang
authors.affiliation: HylaPharm LLC, Lawrence, USA Department of Pharmaceutical Chemistry, The University of Kansas, Lawrence, USA.
authors.forename: Shuang
authors.initials: S
authors.lastname: Cai
authors.affiliation: HylaPharm LLC, Lawrence, USA.
authors.forename: Wai Chee
authors.initials: WC
authors.lastname: Forrest
authors.affiliation: HylaPharm LLC, Lawrence, USA Department of Pharmaceutical Chemistry, The University of Kansas, Lawrence, USA.
authors.forename: Eva
authors.initials: E
authors.lastname: Mohr
authors.affiliation: Department of Pharmaceutical Chemistry, The University of Kansas, Lawrence, USA.
authors.forename: Qiuhong
authors.initials: Q
authors.lastname: Yang
authors.affiliation: HylaPharm LLC, Lawrence, USA Department of Pharmaceutical Chemistry, The University of Kansas, Lawrence, USA lforrest@ku.edu.
authors.forename: M Laird
authors.initials: ML
authors.lastname: Forrest
mesh_terms: D000818:Animals; D004355:Drug Stability; D016014:Linear Models; D013058:Mass Spectrometry / Q000379:methods*; D010984:Platinum / Q000032:analysis* / Q000737:chemistry / Q000493:pharmacokinetics*; D051381:Rats; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D014018:Tissue Distribution
chemical_list: D010984:Platinum
keywords: ICP-MS; Inductively coupled plasma mass spectrometry; bioanalytical method validation; biological matrices; microwave digestion