During FY10, the Clinical Pharmacology Program (CPP) provided support to over 60 clinical trials. This support ranged from sample pickup and processing, to full analytical method development and validation, pharmacokinetic and pharmacogenetic analysis and assistance with trial design. In FY10, the CPP received over 12,000 biological samples including blood, urine and bone marrow aspirate. Upon arrival, all samples are processed, barcoded and frozen for future use. The first priority in characterizing the pharmacokinetics of an anticancer agent is to develop a reliable and reproducible analytical method for quantitating agents in biological fluids and tissues. The CPP utilizes high performance liquid chromatograpy (HPLC) coupled with state-of-the-art detection instruments including mass spectrometers, tandem mass spectrometers (MS/MS) and diode array detectors (for UV absorption) to measure drug concentrations. Following method development, assays are validated according to the FDA Guidelines for Bioanalytical Method Development. The CPP is currently focused on the method development, validation and subsequent human sample analyses for AZD2281, gemcitabine, SNX5422, sorafenib, finasteride, docetaxel, nelfinavir, and clopidogrel. The group has recently validated and published an assay for 17-DMAG, and sample analysis is ongoing in support of a Phase I clinical trial being conducted within the CCR. The CPP has previously developed analytical methods for a wide range of other therapeutics, including depsipeptide, TNP-470, phenylacetate, phenylbutyrate, tamoxifen, UCN-01, CAI, thalidomide, COL-3, suramin, melphalan, erlotinib, perifosine, SU5416, 2ME, MS-275, ketoconazole, and CC5013. A validated LC-MS method was recently developed from our laboratory and currently used in the analysis of SNX2112 and its prodrug SNX5422 on patient samples. Irinotecan drug eluting beads study: an analytical assay is under development and validation for quantitation of irinotecan, SN-38 and SN-38G in porcine and human plasma, using LC-MS-MS technology. Bioanalysis of AZD2281 and Gemcitabine along with Cisplatin: To evaluate the pharmacokinetics (PK) of AZD2281 and gemcitabine as well as to assess for any potential drug-drug interaction, a sensitive and simple LC-MS method was recently developed to simultaneously determine drug concentrations of both AZD2281 and Gemcitabine on patient samples derived from this trial.
NIH ExPorter
NIH ExPorter