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The Pharmacoanalytic Shared Resource (PhASR) supports pre-clinical and clinical drug development at OSUCCC–James by providing high quality, cost-effective and reliable bioanalytical method development, quantitative sample analysis, and pharmacokinetic/pharmacodynamic/pharmacogenetic experimental design and data analysis.
Analytical Method Development and Validation
Proper analytical method development ensures appropriate chromatographic peak shapes, optimal sensitivity and reproducibility of results. Full validation of a newly developed method, based on the Guidance for Industry, Bioanalytical Method Validation published by the U.S. Food and Drug Administration, is completed for all work involving clinical trials, and it is recommended for all methods producing results intended for publication.
PhASR staff offers expertise in developing and validating LC-MS methods. PhASR can also develop other methods and utilize published quantitative methods, when available, as a starting point to save time and cost in method development and validation.
Analyte quantitation requires developing an analytical method optimized for precision and accuracy. For LC-MS methods, this entails appropriate selection of an internal standard, solvents for sample preparation, and LC mobile phases, analytical columns, liquid flow rates, gradients, ion polarity, daughter ions, gas flow rates and other general MS parameters. For some compounds, LC-MS may not be the most appropriate method of quantitation and an alternative detection method should be considered.
The outcome of the Analytical Method Development and Validation service is a validated method for accurate and precise quantitation of a specific compound in a given matrix.
Sample Analysis for General Pharmaceutics/Pharmacology Experimentation
Once an analytical method is developed, compound quantitation can begin. Using validated method procedures, PhASR processes and analyzes samples containing unknown concentrations of a compound.
Samples may arise from biological matrices, such as plasma, urine or feces, or they may come from in vitro systems. The validity of results is ensured by: the method validation process, processing quality control samples, and standard samples – all processed and analyzed in parallel to the unknown samples.
Once a run is complete, PhASR reviews the data to ensure all quality controls fall within the allowed accuracy range and the measured standard sample concentrations produce a linear range for quantitation.
PhASR provides expertise in metabolite and product identification. Knowledge of the metabolic pathways of a drug or drug class is critical in the drug development process, and mass spectrometry provides a means to specifically identify metabolites formed in small quantities in in vitro or in vivo systems.
Both LC and MS conditions are developed to separate the parent compound and metabolites adequately. For cases in which the metabolic pathways are known, specific metabolites may be anticipated, and the mass spectrometer can be tuned to look for these specific compounds. For cases in which the metabolic pathways are not known, searches for all possible metabolites can be conducted.
Experimental Design and Data Analysis
Experimental Design and Data Analysis offers users full access to PhASR’s expertise in pharmacokinetics, specimen preparation strategies and data analysis. The service provides clinical and pre-clinical research expertise in understanding the expected kinetics and fate of a drug and/or its metabolites in a biological system.
By proper design of a pharmacokinetic sampling strategy, representative biological specimens are obtained before, during and after drug administration. Samples are processed and stored appropriately to ensure specimens remain representative of the biological samples originally obtained.
PhASR works closely with the Clinical Treatment Unit to advise on sampling and storage strategies that will provide the highest quality data while considering patient needs and CTU procedures.
After samples are analyzed, PhASR completes appropriate analysis to insure quality of the raw data. The outcome of this service is a carefully designed PK/PD study, which yields data and results that achieve the investigator’s project objectives.
Pharmacokinetic/Pharmacodynamic Data Analysis and Modeling
After samples have been analyzed, PhASR completes an analysis of the data generated. Relevant PK/PD parameters and statistical considerations are defined during the experimental design process, and the data analysis follows the outlined plan.
PhASR staff is highly trained and experienced in PK/PD data analysis and modeling, which ranges from basic statistical comparisons to linear and non-linear data modeling.
The quantity and level of analysis will differ for each project. Analyses could include: a simple comparison of drug concentrations between experimental and control samples sets; a more complex analysis requiring a population PK/PD model to be constructed, validated and verified, then tested for predictive capabilities; model building; or more complex statistical modeling and analysis.
PhASR also offers additional services based on the methodological needs of OSUCCC -James members.
• Global DNA Methylation (GDM)
• Regional DNA Methylation (RDM)
• Quantitation of dNTP/NTP Pools
• Hybridization-based ELISA
• Metabolite/Product Identification
• Drug Binding and Transport