Clinical Pharmacology & Experimental Therapeutics Center
Clinical Pharmacology & Experimental Therapeutics Center
The center provides pharmaceutical expertise to conduct and support preclinical and clinical/translational trials, and postmarketing assessment of pharmaceutical drugs. The Clinical Pharmacology & Experimental Therapeutics Center consists of three core areas of focused research:
- North Texas Clinical Pharmacology Cancer Core (funded in part by the Cancer Prevention and Research Institute of Texas)
- Experimental Therapeutics and Diagnostics Core
- Regulatory Sciences Core
Experimental Therapeutics and Diagnostics Core
We have preclinical resources for researchers and collaborators to develop and test new drugs, enable translational research in drug discovery/development. One of the resources we have is cell disease models. Our cell disease models in cancer and neurodegeneration diseases are designed for drug screening, new therapeutic target exploring as well as drug tolerability and efficacy studies. Another resource is our advanced instrumentation. Three advanced mass spectrometry with established proteomics, metabolomics and epigenetics workflow, we are striving to discover new diagnostics biomarkers of cancer and neurodegeneration diseases with our clinic collaborators.
Primary areas of research focus:
- Pharmacokinetics/Pharmacodynamics
- Drug metabolism
- Drug formulation and delivery
- Drug discovery
- Biomarker identification
- Chemical characterization
- Laboratory space: ~2,500 square feet
- General equipment: analytical balances, pipettes, pH meters, centrifuges, two Labconco CentriVap® systems, two Nitrogen-evaporation systems, two refrigerators (5 ± 3 °C), two freezers (-20 ± 10 °C) and four ultra-freezers (-80 ± 10 °C). The ultra-freezers are continuously monitored and clinical samples are inventoried using FreezerPro® software package. Specialized automated sample preparation equipment includes an Eppendorf epMotion M5073 and a Tomtec Quadra 4® automated liquid handling systems.
- Tissue preparation equipment: Pro Scientific DPS-20 homogenization system (ultrasonic and mechanical homogenization); Leica RM2255 microtome, Leica CM3050S Cryostat, and a Leica LMP6 laser microdissection system.
- Mass spectrometric instrumentation includes: Sciex QTRAP® 6500+, Sciex QTRAP® 7500, Sciex TripleTOF™ 7600, and an Agilent 7700 ICP-MS. The Sciex QTRAP®and TripleTOF™instruments can be interfaced with Shimadzu Nexera UHPLC systems or Eksigent exspert™nano-LC/micro-LC system. Additional gradient liquid chromatographic (HPLC) systems are available with Shimadzu UV/Vis, ELSD and Dionex electrochemical detectors. Specialized analytical software includes Sciex’s Analyst™, PeakView™, SWATH™, and MultiQuant™ software packages.
- Pharmacokinetic modeling software: Certara Phoenix 64 WinNonlin v6.4.
Overall, the Clinical Pharmacology & Experimental Therapeutics Center specializes in conducting pharmacology studies on experimental therapeutics.
Specific capabilities of the Center include:
- Bioanalytical method development
- Bioanalytical method validation
- Blood/Plasma/Serum sample analysis
- Tissue sample analysis / tissue distribution analysis
- Analyte/formulation stability studies
- Automated sample preparation
- Small molecule bioanalytical sample analysis
- Biomolecule bioanalytical sample analysis
- Metals analysis
- Pharmacokinetic determinations
- Targeted metabolite studies
- Chemical characterization of small molecules, biotherapeutics, formulated products and botanical extracts
- Regulatory development input
- Cell disease model for drug screening
Additional services provided by Center faculty:
- Program and protocol development and support
- Analyses and interpretation of PK and PK/PD data
- Population PK analysis for optimal dosing
The Center's analytical laboratory specializes in developing and validating methods for the analysis of both small- and large-molecule pharmaceutical agents, their metabolites, and biomarkers in complex biologic matrices using state-of-the-art bioanalytical techniques.
SCIEX 7500 is a QTRAP Triple Quad" system featured with MRM3 QTRAP scan and an enhanced product ion (EPI) scan. Those are effective scan solutions that removes high background and interferences and can achieve lower detection limits compared to most existing triple quad systems. Especially with MRM3 scans, it offers better specificity and quantitative performance for drug metabolites that share similar structure or similar mass of fragment ions.
ZenoTOF 7600 is a Q-TOF instrument equipped with a hybrid collision cell. The collision cell includes two collision modes -collision induced dissociation (CID) and electron activated dissociation (EAD). EAD (radical) and CID (thermal) collision could produce invaluable complimentary fragmentation maps that significantly increase the identification rate for biomolecule structures.
ZenoTOF 7600 is also a great tool to explore intact proteins with its build-in peak deconvolution software. With the ability to look at the intact proteins, we are easily on the path to explore protein posttranslational modifications and protein-protein interactions.
SCIEX 6500 QTRAP" is a traditional Triple Quad system. QTRAP means the third quadrupole can be configured as a Linear Ion Trap (LIT) to provide simultaneous quantitation and identification without losing the sensitivity.
Our SCIEX 6500 is coupled with a differential ion mobility mass spectrometry SelexION, which provides the unique capability to separate analytes with identical molecular weights and retention times.
This is a contact- and contamination-free method for isolating specific single cells or an area of tissue. This tool allows us to study the biochemical heterogeneity within a tumor or among cells. It captures the spatial profile of quantitative analysis. It also enables single cell metabolomics or proteomics study for cancer as well as other diseases.
Faculty Members
Ronald G. Hall II, Pharm.D., MSCS
Center Director
Associate Professor, Departments of Pharmacy Practice
Ronald.Hall@ttuhsc.edu
Focus of Research: Dose Optimization and Outcomes Research
Dr. Hall serves as the Division Head of Clinical and Translational Research, and Director of the Dose Optimization and Outcomes Research (DOOR) program. Dr. Hall's work has resulted in over 70 peer-reviewed publications. He has collaborated on grants funded by the Cancer Prevention and Research Institute of Texas, National Institutes of Health, Laura W. Bush Institute for Women’s Health, as well as the pharmaceutical industry.
Li Li, Ph.D.
CPRIT Core Director
Assistant Professor, Departments of Pharmacy Practice and Pharmaceutical Sciences
Li.Li@ttuhsc.edu
Focus of Research: Drug Metabolism and Drug Discovery
Dr. Li is a basic science and translational medical researcher who has broad training in analytical chemistry, medicinal chemistry and structural biology. She works closely with the North Texas cancer research community to provide comprehensive analytical support through the North Texas Clinical Pharmacology Cancer core.
William “Trey” Putnam, Ph.D., RAC
Investigator
Professor, Departments of Pharmacy Practice and Pharmaceutical Sciences
Trey.Putnam@ttuhsc.edu
Focus of Research: Clinical Pharmacology and Metabolism
Dr. Putnam's work in clinical pharmacology and experimental therapeutics over the past 20+ years has led to the development, approval and commercialization of numerous drugs and biologics for various clinical indications. His experiences as a faculty at research-intensive colleges of pharmacy, Group Leader for bioanalytical chemistry at a leading non-for-profit research institute, and General Manager for an international drug-development focused scientific and regulatory consulting firm provide him with a broad, in-depth perspective uncommon in analytical laboratories.
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Ronald G. Hall II, Pharm.D., MSCS
Center Director
Ronald.Hall@ttuhsc.edu