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The Pharmacoanalytical Shared Resource

Summary:

The Pharmacoanalytic Shared Resource (PhASR) supports pre-clinical and clinical drug development at Ohio State by providing high quality and cost-effective bioanalytical method development, quantitative sample analysis, and pharmacokinetic / pharmacodynamic experimental design, data analysis and modeling.

Expertise among PhASR personnel includes quantitative pharmacology; bioanalytical methodology, design and conduct of pharmacokinetic/pharmacodynamic studies in animal disease models and in humans enrolled in clinical trials; data analysis and modeling of PK/PD data to inform drug development decisions. PhASR personnel are available for consultation on clinical or pre-clinical PK/PD experimental design and analysis.

Affiliations:

People:

    Resources:

    Instruments

    • Liquid Chromatography/Mass Spectrometry System Details ( Liquid chromatography mass spectrometry platform )

      Liquid Chromatography/Mass Spectrometry System Details: Primary PhASR equipment comprises four liquid chromatography/mass spectrometry (LC-MS) systems.

    • ThermoFinnigan TSQ Altis ( Liquid chromatography mass spectrometry platform )

      ThermoFinnigan TSQ Altis: A triple-quadrupole mass spectrometer equipped with heated electrospray ionization probe and coupled to a Thermo Vanquish ultra-high pressure liquid chromatography system (UHPLC, degasser, quaternary pumps, heated column compartment, autosampler).

    • ThermoFinnigan TSQ Quantiva ( Mass spectrometer )

      ThermoFinnigan TSQ Quantiva: A triple-quadrupole mass spectrometer with ultra-high-sensitivity (APCI and heated ESI ionization probes) coupled with a Dionex RSLCnano system (with ternary loading pumps, quaternary nano-flow pumps, degasser, temperature-controlled autosampler and column compartment). This system also incorporates an Easy-Spray nano-flow electrospray ionization source to achieve the maximal sensitivity possible for accurate quantification of small molecules, peptides or other biomolecules in complex biological matrices or in small sample quantities.

    • ThermoFinnigan TSQ Quantum Discovery Max ( Mass spectrometer )

      ThermoFinnigan TSQ Quantum Discovery Max: A triple-quadrupole mass spectrometer with ESI and APCI ionization probes and a ThermoFisher Acella ultra-high-performance LC system (degasser, quaternary pumps, and photo-diode array detector), which includes an autosampler that is expandable for multiplexing, online extraction and high-throughput analysis.

    • ThermoFinnigan TSQ Quantum Ultra ( Mass spectrometer )

      ThermoFinnigan TSQ Quantum Ultra: A triple-quadrupole mass spectrometer with extended mass range and heated electrospray ionization probe connected to a Dionex RSLCnano system (with ternary loading pumps, quaternary nano-flow pumps, degasser, temperature-controlled autosampler and column compartment).

    Resource Collection

    • The Ohio State University Comprehensive Cancer Center Collection ( Resource Collection )

      The OSUCCC – James Shared Resources and core facilities provide specialized services to cancer researchers. They offer cost-effective, state-of-the-art technology and instrumentation; expert guidance and training; and clinical, administrative and technical support.

    Services

    • Analytical Method Development and Validation for Quantitative Assays ( Data analysis service )

      The PhASR staff offers expertise in developing and validating quantitative assays optimally suited for small molecules and peptides (LC-MS/MS), protein therapeutics (ELISA) and oligonucleotide therapeutics (ELISA and qRT-PCR). Proper analytical method development ensures appropriate understanding of factors that could influence results obtained with bioanalytical measurements or with measures of drug activity. For example, lack of understanding about compound solubility and stability may lead to incorrect conclusions from in vitro or in vivo pharmacokinetic or pharmacodynamic studies. 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 in non-clinical studies.

      Accurate and sensitive quantification of drugs, metabolites and endogenous biomolecules requires developing and validating analytical methods optimized for precision and accuracy. For LC-MS methods, this involves appropriate selection of internal standards, solvents or solid-phase media for efficient sample extraction, 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 within a given matrix (e.g. blood, plasma, tissue, urine, etc.).

    • Experimental Design and Data Analysis for Drug Pharmacokinetics and Pharmacodynamics ( Data analysis service )

      Experimental Design and Data Analysis offers users full access to the PhASR’s expertise in characterizing relationships between drug pharmacokinetics and pharmacodynamics, including specialized needs for sample collection, specimen preparation and storage, data analysis and statistical modeling. 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. Through 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 they remain representative of the biological samples originally obtained.

      For clinical studies, the 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 clinical procedures.

      After samples are analyzed, the PhASR completes appropriate analysis to ensure the 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.

    • Metabolite/Product Identification ( Material analysis service )

      The 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.

    • Pharmacokinetic/Pharmacodynamic Data Analysis and Modeling ( Data analysis service )

      After samples have been analyzed, the PhASR can complete analyses 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.

      The PhASR staff are highly trained and experienced in PK/PD data analysis and modeling, which ranges from basic statistical comparisons to linear and non-linear, mixed-effects data modeling. The quantity and level of data analysis will differ for each project. Analyses could range from a simple comparison of drug concentrations between experimental and control samples sets to a more complex analysis requiring a population PK/PD model to be constructed, qualified and validated for predictive capabilities.

    • Sample Analysis for General Pharmaceutics/Pharmacology Experimentation ( Material analysis service )

      Once an analytical method is developed, compound quantitation can be achieved. Using validated method procedures, the PhASR processes and analyzes samples containing unknown concentrations of the compounds of interest. 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, the PhASR reviews the data to validate the analytical run and ensure that quality control sample measurements fall within the allowed accuracy range and that the measured standard sample concentrations produce a linear range for quantitation.


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    Last updated: 2020-12-16T09:43:48.532-05:00

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    The eagle-i Consortium is supported by NIH Grant #5U24RR029825-02 / Copyright 2016