Pharmacoanalytical

Ohio State University, Columbus OH

Investigators

Linked publications, trials & patents

Abstract

PROJECT SUMMARY (See instructions): The Ohio State University Comprehensive Cancer Center (OSUCCC) Pharmacoanalytical Shared Resource (PhASR) has been in development since 2004. PhASR provides bioanalytical method development, quantitative sample analysis, and pharmacokinetic/pharmacodynamic (PK/PD) experimental design and data analysis to support pre-clinical and clinical cancer drug development. PhASR's objectives are to provide: 1) high-quality, state-of-the-art analytical expertise and instrumentation for quantitation of drugs and metabolites in biological specimens at cost-competitive rates; 2) PK/PD data for incorporation into clinical decision-making; and 3) expertise in PK/PD study design and data interpretation to support submission of clinical protocols, grants, and publications. PhASR is directed by Dr. Kenneth K. Chan, with additional support from Technical Director, Dr. Mitch A. Phelps. An additional staff of 2.70 full-time employees provides support for sample processing, method development and PK/PD data analysis and modeling. Outstanding institutional support is provided by the OSUCCC and College of Pharmacy's Division of Pharmaceutics that houses the fully-equipped pharmaceutical research laboratories of Drs Chan and Phelps which comprise PhASR. Major equipment in PhASR includes 3 LC-MS systems and 2 stand-alone LC-UV systems ideally suited for drug quantitation and metabolite identification. These systems include a quadrupole-time-of-flight and two triple-quadrupole mass spectrometers, one of which is supported by an ultra-high pressure liquid chromatography system expandable for automated sample processing and high throughput enalysis. Additional LC-MS systems to develop and run biological correlative assays are available. By leveraging outstanding institutional partnerships, PhASR is able to offer its services to OSUCCC members at reduced rates. In the past 12 months PhASR staff has analyzed more than 2,600 samples and has logged nearly 1,700 hours for analytical method development and PK/PD experimental design and data analysis. Neariy 95% of this activity supported 27 members in 5 of the 6 programs within the OSUCCC. Recent highlights of work by PhASR researchers include design of an active flavopiridol dosing schedule and pharmacokinetic modeling of data from 8 clinical trials; development, validation and application of ultrasensitive assays (pM) to support clinical investigations of Bcl-2 and ribonucleotide reductase targeted antisense therapies (G3139 and GTI-2040); validation and application of methods for quantitation of low dose decitabine and resulting intracellular endogenous nucleoside and drug phosphates and global and regional DNA methylation; and pre-clinical pharmacokinetic and metabolism studies of the novel natural product, silvestrol, now in pre-clinical development by the OSUCCC and the NCI. In its short time as a developing resource, PhASR has made these and other significant contributions resulting in high impact publications, grant proposals and funding for OSUCCC investigators. Institutional support and OSUCCC investigators' recognition of the quality of PhASR capabilities and services have insured the continued growth and success of this highly valued shared resource.