During FY17, the Blood Processing Core (BPC) provided support to over 90 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 FY17, the CPP processed over 28,000 biological samples including blood, urine, cerebrospinal fluid, pleural effusion aspirate, saliva, bone marrow aspirate, and ascites. Upon arrival, all samples are processed according to the clinical protocol (per standard operating procedures), entered into a database for sample handling and storage purposes and cataloged into a software system. The BPC provides a broad range of services including the development and validation of procedures for specimen processing, analyses, and DNA extraction to establish protocols that optimize specimen integrity and consistency. 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 Clinical Pharmacology Program (CPP) utilizes high performance liquid chromatography (HPLC) coupled with state-of-the-art detection instruments including mass spectrometers, tandem mass spectrometers (MS/MS), diode array detectors (for UV absorption), and fluorescence detection to measure drug concentrations. Following method development, assays are validated according to the FDA Guidelines for Bioanalytical Method Development. Over the years, the CPP has developed analytical methods for a wide range of therapeutics, numerous which have been published, including depsipeptide, TNP-470, phenylacetate, phenylbutyrate, tamoxifen, UCN-01, CAI, thalidomide, COL-3, suramin, melphalan, erlotinib, perifosine, SU5416, 2ME, MS-275, ketoconazole, lenalidomide, romidepsin, AZD2281 and gemicitabine, sorafenib, finasteride, nelfinavir, 17-DMAG, clopidogrel and and its MPB-derivatized active thiol-metabolite (CAMD), Hsp90 inhibitor PF-04928473, irinotecan (its active metabolite SN38, and glucuronidated SN38), Trk kinase inhibitor AZD7451, pomalidomide, olaparib, sorafenib, belinostat, cediranib, abiraterone, cabozantinib, carfilzomib, midazolam, lapatinib, temozolomide, perifosine, and valproic acid. We have recently developed a sensitive and selective ultra-high performance liquid chromatography-tandem mass spectrometric (UHPLC-MS/MS ) method for the quantification of temozolomide in nonhuman primate (NHP) plasma, cerebrospinal fluid (CSF), and brain extracellular fluid (ECF) following microdialysis.
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