title: Quantification and clinical application of carboplatin in plasma ultrafiltrate.
abstract: Carboplatin is a chemotherapy drug used in a variety of cancers with the primary toxicity being exposure-dependant myelosuppression. We present the development and validation of a simple, robust inductively coupled plasma mass spectrometry (ICP-MS) method to measure carboplatin in plasma ultrafiltrate. Plasma ultrafiltrates samples were prepared using Amicon Ultra 30,000da cut-off filters and then diluted with ammonia EDTA before ICP-MS analysis. The assay was validated in the range 0.19-47.5mg/L carboplatin in ultrafiltrate. The assay was linear (r2>0.9999), accurate (<6% bias, 12% bias at LLOQ) and precise (intra- and inter-day precision of <3% coefficient of variation). No matrix effects were observed between plasma ultrafiltrate and aqueous platinum calibrators and recovery was complete. The assay was applied to 10 clinical samples from patients receiving carboplatin. Incurred sample reanalysis showed reproducible values over 3 analysis days (<6% CV). As plasma stability prior to ultrafiltration has been a major concern in previous clinical studies this was studied extensively at room temperature (22°C) over 24h. Carboplatin was found to be stable in both spiked plasma (n=3) and real patient samples (n=10) at room temperature for up to 8h before ultrafiltration. This makes routine measurement of carboplatin concentrations in clinical settings feasible.
authors.affiliation: Canterbury Health Laboratories, Christchurch, New Zealand. Electronic address: kim.downing@cdhb.health.nz.
authors.forename: Kim
authors.initials: K
authors.lastname: Downing
authors.affiliation: Canterbury Health Laboratories, Christchurch, New Zealand.
authors.forename: Berit Packert
authors.initials: BP
authors.lastname: Jensen
authors.affiliation: Canterbury Health Laboratories, Christchurch, New Zealand.
authors.forename: Sue
authors.initials: S
authors.lastname: Grant
authors.affiliation: Department of Oncology, Christchurch Hospital, Christchurch, New Zealand.
authors.forename: Matthew
authors.initials: M
authors.lastname: Strother
authors.affiliation: Canterbury Health Laboratories, Christchurch, New Zealand.
authors.forename: Peter
authors.initials: P
authors.lastname: George
mesh_terms: D000970:Antineoplastic Agents / Q000097:blood / Q000737:chemistry; D002138:Calibration; D016190:Carboplatin / Q000097:blood* / Q000737:chemistry*; D004355:Drug Stability; D006801:Humans; D009944:Organoplatinum Compounds / Q000097:blood / Q000737:chemistry; D010949:Plasma / Q000737:chemistry*; D015203:Reproducibility of Results; D014462:Ultrafiltration / Q000379:methods
chemical_list: D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; D016190:Carboplatin
keywords: Carboplatin; ICP-MS; Platinum; Stability; Therapeutic drug monitoring; Ultrafiltrate