The broad, long-term objectives of the Clinical Pharmacology and Analytical Chemistry Core are to provide a full spectrum of pharmacologic support for HIV/AIDS-related research of the UNC CFAR. Members of the Clinical Pharmacology and Analytical Chemistry Core proactively engage UNC CFAR investigators to identify and deliver services essential for highly productive design, management, analysis and publication of HIV/AIDS research. The Core contributes to the framing of hypotheses, development of study designs, preparation of grant applications, selection or creation of best analytical chemistry and pharmacometric methods, facilitating multidisciplinary and translational approaches to the design of and conduct of clinical studies, and delivery of preclinical or clinical analyses.
Investigators new to HIV/AIDS research receive highest priority for Core services. Strong institutional support from the School of Pharmacy allows the Core to take full advantage of existing infrastructure, resources and contacts with faculty renowned for their expertise in specialized fields of pharmacology. The Core supports drug quantification in a variety of matrices with 6 AB Sciex 5000 Triple Quadrupole Mass connected to Shimadzu HPLC systems running on Analyst software and an infrared matrix assisted laser desorption electrospray ionization (IR-MALDESI) imaging source coupled to a Thermo QExactive/H-ESI II Bundle mass spectrometer similar to that housed in the inventor of this technology’s laboratory (David Muddiman, North Carolina State University).
CPAC Laboratory Aims
Aim 1: Provide access to a diverse array of cost-effective services for pharmacology research.
Aim 2: Stimulate, develop and disseminate new innovative technologies and services to enhance HIV/AIDS research.
Aim 3: Support priority CFAR initiatives and goals and collaborative research.
Aim 4: Develop and promote synergistic relationships between the UNC CFAR Cores and Working Groups, and other CFAR.
Aim 5: Provide clinical pharmacology, pharmacometric, and analytical chemistry training, mentoring, and education, and outreach.
Aim 6: Engage in evaluation and strategic planning.
CPAC Validates Novel Assay to Measure Antiretrovirals in Dried Blood Spot for Adherence Monitoring
The Clinical Pharmacology Core has recently developed and validated a sensitive, multiplex LC-MS/MS assay to measure the intracellular metabolites of the 3 most commonly prescribed NRTIs (tenofovir, emtricitabine, and lamivudine) in dried blood spots collected from patients on therapy. This assay allows investigators to monitor adherence in clinical trials with the convenience of dried blood spot sampling, storage and shipping. The addition of lamivudine, which is generically available, opens up opportunity for international investigations. Our methods and findings are in press in the Journal of Pharmaceutical and Biomedical Analysis (Schauer et al. Validation of an LC-MS/MS Assay to Simultaneously Monitor the Intracellular Active Metabolites of Tenofovir, Emtricitabine, and Lamivudine in Dried Blood Spots. JPBA. In press).
Acknowledgement, Recognition and Future Service
All work provided by the UNC CFAR Clinical Pharmacology and Analytical Chemistry Core which is included in a publication should acknowledge the contribution of the Core. Proper acknowledgment enables us to obtain financial and other support so that we can continue to provide essential services in the best ways possible. It would be appreciated if you sent a copy of the accepted manuscript, published paper, or title of grant application to email@example.com. This will allow us to demonstrate our impact to the research community.
Angela DM Kashuba, B.Sc.Phm., Pharm.D., DABCP, FCP
After obtaining her Bachelor of Science in pharmacy at the University of Toronto, Angela Kashuba, Pharm.D., completed a general practice residency at Women’s College Hospital, and practiced as a critical care pharmacist at Mount Sinai Hospital, in Toronto, Ontario. Kashuba received her Pharm.D. from the State University of New York at Buffalo and completed postdoctoral pharmacology training at the Clinical Pharmacology Research Center at Bassett Healthcare in Cooperstown, New York.
Kashuba joined the UNC-Chapel Hill faculty in 1997. She was named the John and Deborah McNeill, Jr. Distinguished Professor in 2013 and appointed chair of the Division of Pharmacotherapy and Experimental Therapeutics in 2015. She serves as director of the UNC Center for AIDS Research Clinical Pharmacology and Analytical Chemistry Core, and director of the Analytical Chemistry Laboratory for the Verne S. Caviness General Clinical Research Center. She is a diplomat of the American Board of Clinical Pharmacology. Research Kashuba’s research interests focus on the clinical pharmacology of antiretroviral agents used in the treatment of HIV infection. Specifically, she is investigating the role of antiretroviral therapy in preventing the transmission of HIV, determining optimal dosing and drug combinations for the treatment of HIV infection, understanding and predicting drug-drug and drug-cytokine interactions and adverse effects, and role of sex and ethnicity in drug disposition.
3318 Kerr Hall
Chapel Hill, NC
Office Phone: 919-966-9998
Mackenzie Cottrell, Pharm.D., MS
Assistant Core Director
Mackenzie Cottrell is a Research Assistant Professor in the Division of Pharmacotherapy and Experimental Therapeutics at UNC Eshelman School of Pharmacy. She is a Board Certified Pharmacotherapy Specialist and an American Academy of HIV Medicine™ accredited HIV Pharmacist. Her research focuses on describing pharmacokinetic/pharmacodynamic relationships in mucosal tissues for antiretrovirals being used in HIV prevention and cure interventions.
Office Phone: 919-843-7806
Elias Rosen, Ph.D.
Imaging Mass Spectrometry Scientist
Elias Rosen’s research focuses on the development of methods to measure intracellular distribution of therapeutics and their metabolites in a variety of biological matrices using mass spectrometry imaging. He is currently quantifying the penetration of drugs relevant to HIV treatment and eradication into putative viral reservoirs, and combining this approach with traditional imaging modalities to evaluate efficacy of experimental treatment regimens.
Office Phone: (919) 966-9998
Heather Prince, MPA, PA-C
Clinical Study Specialist
Heather Prince joined the UNC CFAR in 2008. She holds an AS and BA in Microbial Genetics from Peace College, and an MPA from Eastern Virginia Medical School. She has completed post-graduate surgical training at Eastern Virginia Medical School, Emory University, Harvard University and John Hopkins University. She is a Certified Clinical Research Professional who oversees all clinical aspects of research studies, from protocol development to implementation and patient care.
Office Phone: (919) 962-5344
John H. Dohnal, BS, MBA
Laboratory Operations Manager
John Dohnal joined the UNC CFAR in 2014 and brings 20 years of management and 13 years of quality experience to the Kashuba Lab. Dohnal received a BS in biochemistry from Florida State University and an Executive Masters of Business Administration with concentration in Health Sector Management from the Duke Fuqua School of Business. Dohnal’s focus is ensuring laboratory safety, supervising work study students and interns, sample chain of custody, streamlining laboratory work flows, automation of data processes, creating and maintaining a robust community outreach and social media presence, and continuous improvement in the lab.
Office Phone: (919) 843-7806
Hannah Bryan, BS
Hannah Bryan holds a BS in Animal Science from NC State University. Prior to joining the UNC CFAR in 2017, she spent six years conducting both discovery and regulated research for a Clinical Research Organization in Research Triangle Park. Hannah currently oversees all quality control aspects of the analytical study data that is generated in the lab.
Office Phone: 919-843-2791
Craig Sykes, MS
Bioanalytical Method Development Scientist
Craig Sykes holds a BS in chemistry from UNC-Wilmington and an MS in analytical chemistry from UNC-Chapel Hill. Prior to joining the UNC CFAR in 2011, he spent nine years developing GLP-compliant assays for several contract research organizations (CROs). He has extensive experience in LC-MS/MS method development, method validation, and sample analysis in a regulated environment. He is responsible for the development and validation of bioanalytical assays for the UNC CFAR.
Office Phone: 919-843-2791
Nicole White, BS
Bioanalytical Research Specialist
Nicole White has been an outstanding analytical chemist at UNC since 1994, and she has received awards in recognition of her exceptional service. White oversees analytical methods and standard operating procedures in the laboratory. She has been with the UNC CFAR since 2007.
Office Phone: 919-843-1016
Amanda Schauer, BS
Bioanalytical Research Specialist
Amanda Schauer joined the UNC CFAR in January 2015 with a BA in chemistry from NC State University. Before joining UNC in 2015, she worked for a CRO company doing sample analysis and quality control in a GLP-regulated environment. Schauer is responsible for LC-MS/MS analytical methods and sample analysis in the laboratory.
Office Phone: (919) 966-9998
Brian Van Home, BS
Bioanalytical Research Specialist
Brian Van Horne received a BS in Chemistry from the State University of New York at Oswego. Before joining the Kashuba lab in 2017, he worked as a Lab Technician in a toxicology lab in Syracuse. He is currently working as one of our Research Specialists.
Offfice Phone: (518) 926-8062
Clinical Pharmacology Services
The preclinical and clinical samples that are analyzed in our lab can be divided into 3 categories:
1. Tier 1 – Discovery (preclinical data, preliminary data, research studies)
2. Tier 2 – Qualified (preclinical or clinical research purposes suitable for publication, method qualified by 1 day of Precision and Accuracy)
3. Tier 3 – Validated (clinical studies for FDA submission, TDM, PT, method fully validated according to FDA guidelines)
The samples the CPAC laboratory analyzes come in a variety of human and animal matrices, including, but not limited to:
• peripheral blood mononuclear cells (PBMCs)
• red blood cells (RBCs)
• cervical tissue*
• rectal tissue*
• vaginal tissue*
• adipose tissue*
• rectal fluid
• cerebrospinal fluid (CSF)
• breast milk
• cervicovaginal fluid (CVF)
• dried blood spots (DBS)
Analysis costs start at $80 per sample. *Tissue analysis costs start at $100 per sample. If weights of tissues samples are not provided by the investigator, tissues can be weighed in the CPAC lab for an additional fee. QA/QC charges are calculated based on the service level (Tier 1-3) and added to the base sample analysis costs. Contact firstname.lastname@example.org for budgeting inquiries.
If any facility personnel makes a substantial intellectual and/or experimental contribution to a publication they deserve recognition just as any other co-author. This is essential for the professional development of our staff. We recommend scientists follow the “ABRF Recommended Guidelines for Authorship on Manuscripts.” Services provided on a fee-for-service basis does not diminish the importance of our scientists impacting your research.
The UNC-Duke Collaborative Clinical Pharmacology T32 Postdoctoral Training Program is a collaboration between the UNC Eshelman School of Pharmacy, the UNC Institute for Drug Safety Sciences and the Duke Clinical Research Institute to prepare clinician-scientists to become leaders in clinical pharmacology research. More information about the program can be found at: https://pharmacy.unc.edu/academics/fellowships/unc-duke-collaborative-clinical-pharmacology-t32-postdoctoral-training-program/
Pharmacology Training Table of Contents
|Training Category||Module Title||Duration||Video Link|
|Overview||What is Pharmacokinectics||12:20||https://vimeo.com/220303663|
|Overview||ART in older patients||11:02||https://vimeo.com/227701376|
|Overview||The Pharmacology of PrEP||11:51||https://vimeo.com/227701454|
|Absorption||Principles of Absorption||14:20||https://vimeo.com/220988942|
|Disposition||Principles of Disposition||12:22||https://vimeo.com/220988985|
|Metabolism and Excretion||Principles of Drug Metabolism and Excretion||12:57||https://vimeo.com/220989054|
|Class Specific Pharmacology||Disposition of NNRTIs||15:26||https://vimeo.com/230905734|
|Class Specific Pharmacology||Disposition of NRTIs||16:54||https://vimeo.com/230905755|
|Class Specific Pharmacology||Disposition of PIs and boosting||14:43||https://vimeo.com/230905768|
|Population PK and Modeling||Inter and Intra-variability in PK||11:02||https://vimeo.com/220309797|
|Population PK and Modeling||Population Pharmacokinectics||14:01||https://vimeo.com/227701441|
|Population PK and Modeling||PBPK Modeling||10:11||https://vimeo.com/229706801|
|Drug Interactions||The Basics of Drug Drug Interactions||12:28||https://vimeo.com/220309881|
|Drug Interactions||Absorption Interactions||11:56||https://vimeo.com/236571317|
|Drug Interactions||Renal Interactions||9:20||https://vimeo.com/236571344|
|Drug Interactions||Renal and Hepatic Interactions||7:51||https://vimeo.com/236571316|
|Drug Interactions||Metabolic Interactions||11:04||https://vimeo.com/236571334|
|Drug Interactions||Drug Interactions in an Aging HIV Population||11:01||https://vimeo.com/227701287|
Have questions about the videos? Ask one of our CPAC experts
Use our service ticket request system (http://unccfar.org/submit-service-request/) to submit a ticket by selecting “Other” under “Service you require” and providing a brief description of the question.