Matthew Bryant Ph.D.

Lead Chemist — Office of Scientific Coordination

Matthew Bryant, Ph.D.
(870) 543-7391
NCTRResearch@fda.hhs.gov

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Background

Matthew Bryant studied chemistry at the Rochester Institute of Technology in upstate New York and graduated with a bachelor’s in 1982. There he participated in a cooperative education program that included working as an applications chemist at Bausch and Lomb, Inc. Dr. Bryant then attended the Massachusetts Institute of Technology in Cambridge, Massachusetts and received his Ph.D. in toxicology in 1987 for work on the use of hemoglobin adducts of aromatic amines and their application to exposure assessment and biochemical epidemiology. Dr. Bryant furthered his training as an FDA staff fellow at NCTR, studying advanced mass-spectrometry techniques and their use in the quantification of hemoglobin and DNA adducts as biomarkers of carcinogen exposure. He joined the Chemical Industry Institute of Toxicology in Research Triangle Park, NC to conduct research on carcinogen-exposure assessment and to manage analytical chemistry laboratories in mass spectrometry, analytical services, and inhalation exposure. Dr. Bryant joined Schering-Plough Research Institute in New Jersey in 1992 to manage a bioanalytical chemistry group supporting drug discovery and development projects. He participated in new drug-discovery research as a project manager. It was there that he collaborated with synthetic chemistry and biochemistry groups to optimize the drug metabolism and pharmacokinetic properties of candidate molecules in therapies for :

allergy
cardiovascular
central nervous system
oncology

After increasing responsibilities as a laboratory head and project manager, Dr. Bryant accepted a position at Bayer in New Haven, Connecticut as Deputy Director of a Drug Metabolism and Pharmacokinetic group supporting new drug-discovery and early-development research. He was responsible for the exploration and implementation of new technologies and approaches to perform rapid pharmacokinetic evaluation of new small-molecule chemical entities for several therapeutic areas. Dr. Bryant then applied this experience at Covance Laboratories in Madison, Wisconsin as Associate Director in Drug Metabolism and Pharmacokinetics, where he:

Managed the group for in vitro metabolism (GLP, non-GLP, discovery).
Managed the group that provided bioanalytical/HPLC/mass spectrometry support (including metabolite identification and pharmacokinetic screening).
Played a key role in developing strategies for new business, managing resources, and providing scientific oversight for critical issues.
Consulted with clients on Drug Metabolism and Pharmacokinetic issues for individual studies and drug-development programs.

Dr. Bryant continued his work in new drug-discovery research as the Director of Drug Metabolism and Pharmacokinetics, at the Cardiovascular and Urogenital Center for Excellence in Drug Discovery at GlaxoSmithKline. He also worked as the Director of Early Bioanalytics and Technology, at the Novartis Institutes for BioMedical Research. His research efforts have contributed to the advancement of a number of compounds from discovery phase into drug development and even beyond the clinic to marketed products. After nearly 20 years working for the pharmaceutical industry, Dr. Bryant returned to NCTR in his current position as lead chemist in the Division of Biochemical Toxicology. His group of analytical chemists collaborates with other NCTR scientists on studies sponsored by FDA, National Toxicology Program, and Center for Tobacco Products. A key objective of his work is to implement new and improved analytical technology to ensure that studies at NCTR are conducted with exemplary quality.

Research Interests

Dr. Bryant collaborates with researchers on key aspects of toxicology studies, including verifying the identity and purity of test articles using analytical chemistry techniques. Concentration verification of test substances has been a key concern, especially when natural products or mixtures are being studied. Characterization of more complex mixtures, such as tobacco smoke, is of particular interest. Dr. Bryant’s group makes use of a variety of analytical methods to analyze a diverse range of drugs and toxic compounds in dose vehicles, such as drinking water, diet pellets or powder, oral or intravenous solutions. The characterization of test articles in complex mixtures is a focus of collaborations with the inhalation toxicology facility that utilizes tobacco smoking machines or other specialized test article delivery apparatus. Evaluating the stability or homogeneity of test articles in dose vehicles or formulations is important, not just for simple solutions, but for complex vehicles such as creams or diet admixtures. Sensitive analytical methods are used to test for trace amounts of the test article, or potential contaminants in background materials, including bedding, diet, drinking water, and cages. Animal studies often require that proper amounts of certain nutrients (vitamins, protein, fat) are in the food, or that certain known or suspected contaminants (pesticides, trace metals) are below a target level.

Dr. Bryant is interested in:

Bioanalytical methodology, especially the use of hyphenated mass spectrometry (e.g. HPLC/MS, GC/MS and MS/MS technology) for the trace level analysis of compounds and/or their metabolites in plasma, urine, and tissues. Applications of such analytical methods to toxicology, biochemical epidemiology, and drug discovery and development have been a key area for study.
The use of electrophilic metabolites of carcinogens with nucleophilic target molecules, such as DNA, surrogate blood proteins hemoglobin, and albumin, as tools for studying the mechanism of their toxic effects in vivo. In particular, he has studied the use of sensitive GC/MS techniques to quantify hemoglobin adducts of carcinogenic aromatic amines and applications to exposure assessment and biochemical epidemiology.
Research that seeks to enhance the success rate of drugs by optimizing their ADME (absorption, distribution, metabolism, excretion) or pharmacokinetic properties. Research can often be done to select the best compounds based on their biophysical properties, such as solubility or permeability, or through screening assays that seek to optimize absorption or biological half-life. Once the limiting ADME or toxicology (ADMET) issue is identified, screening assays are used to select the best compounds that not only are efficacious, but have optimized ADMET properties. Such assays include solubility, absorption, P450 inhibition, protein binding, and permeability or in vitro (microsomal) stability. Fast pharmacokinetic studies are conducted in animal models to help select compounds for more costly efficacy studies in key animal models for the specific disease category. Such PK screening assays require the use of modern bioanalytical techniques, such as HPLC tandem MS analysis to screen many compounds in various chemical series. Feedback is often provided to synthetic chemistry groups that utilize this structure-activity relationship data to improve the molecules. Only compounds with the best in vitro ADMET properties or in vivo pharmacokinetics are advanced for efficacy or more detailed pharmacokinetic studies in animal models, before they are recommended for development as full clinical candidates. The role of drug metabolism and pharmacokinetics, combined with modern bioanalytical assays, has improved the success rate for drug candidates in clinical studies.

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Selected Publications

The Role of CYP 3A4 and 1A1 in Amiodarone-Induced Hepatocellular Toxicity.
Wu Q., Ning B., Xuan J., Ren Z., Guo L. and Bryant M.
Toxicol Lett. 2016 Jun 24, 253:55-62.

Differential Effects of Silver Nanoparticles and Silver Ions on Tissue Accumulation, Distribution, and Toxicity in the Sprague Dawley Rat Following Daily Oral Gavage Administration for 13 Weeks.
Boudreau M., Imam M., Paredes A., Bryant M., Cunningham C., Felton R., Jones M., Davis K. and Olson G.
Toxicol Sci. 2016 Mar, 150(1):131-60.

Effects of Maternal and Lactational Exposure to 2-Hydroxy-4-Methoxybenzone on Development and Reproductive Organs in Male and Female Rat Offspring.
Nakamura N., Inselman A., White G., Chang C., Trbojevich R., Sephr E., Voris K., Patton R., Bryant M., Harrouk W., McIntyre B., Foster P. and Hansen D.
Res B Dev Reprod Toxicol. 2015 Jun, 104(3):140.

Toxicity Evaluation of Bisphenol A Administered by Gavage to Sprague Dawley Rats From Gestation Day 6 Through Postnatal Day 90.
Delclos K., Camacho L., Lewis S., Vanlandingham M., Latendresse J., Olson G., Davis K., Patton R., Gamboa da Costa G., Woodling K., Bryant M., Chidambaram M., Trbojevich R., Juliar B., Felton R. and Thorn B.
Toxicol Sci. 2014 May, 139(1):174-97

Supported Liquid Extraction in Combination with LC-MS/MS for High-Throughput Quantitative Analysis of Hydrocortisone in Mouse Serum.
Wu S., Li W., Mujamdar T., Smith T., Bryant M. and Tse FL.
Biomed Chromatogr. 2010 Jun, 24(6):632-8.

A Sensitive and High-Throughput LC-MS/MS Method for the Quantification of Pegylated-Interferon-α2a in Human Serum Using Monolithic C18 Solid Phase Extraction for Enrichment.
Yang Z., Ke J., Hayes M., Bryant M. and Tse F.
J Chromatogr B Analyt Technol Biomed Life Sci. 2009 Jun 15, 877(18-19):1737-42

Metabolism-Based Identification of a Potent Thrombin Receptor Antagonist.
Clasby M., Chackalamannil S., Czarniecki M., Doller D., Eagen K., Greenlee W., Kao G., Lin Y., Tsai H., Xia Y., Ahn H., Agans-Fantuzzi J., Boykow G., Chintala M., Foster C., Smith-Torhan A., Alton K., Bryant M., Hsieh Y., Lau J. and Palamanda J.
J Med Chem. 2007, 50(1):129-38.

A Novel Approach to Perform Metabolite Screening During the Quantitative LC-MS/MS Analyses of In Vitro Metabolic Stability Samples Using a Hybrid Triple-Quadrupole Linear Ion Trap Mass Spectrometer.
Shou W., Magis L., Li A., Naidong W. and Bryant M.
J. Mass. Spectrom. 2005, 40(10): 1347-56.

Identification of a Novel, Orally Bioavailable Histamine H(3) Receptor Antagonist Based on the 4-Benzyl-(1H-Imidazol-4-yl) Template.
Aslanian R., Mutahi M., Shih N., McCormick K., Piwinski J., Ting P., Albanese M., Berlin M., Zhu X., Wong S., Rosenblum S., Jiang Y., West R., She S., Williams S., Bryant M. and Hey J.
Bioorg Med Chem Lett. 2002, 12(6):937-41.

Direct Cocktail Analysis of Drug Discovery Compounds in Pooled Plasma Samples Using Liquid Chromatography-Tandem Mass Spectrometry.
Hsieh Y., Bryant M., Brisson J., Ng K. and Korfmacher W.
J. Chromatog. B Analyt. Technol. Biomed. Life Sci. 2002, 767 (2): 353-362.

Antitumor Activity of SCH 66336, An Orally Bioavailable Tricyclic Inhibitor of Farnesyl Protein Transferase, In Human Tumor Xenograft Models and Wap-ras Transgenic Mice.
Liu M., Bryant M., Chen J., Lee S., Yaremko B., Lipari P., Malkowski M., Ferrari E., Nielsen L., Prioli N., Dell J., Sinha D., Syed J., Korfmacher W., Nomeir A., Lin C., Wang L., Taveras A., Doll R., Njoroge G., Mallams A., Remiszewski S., Catino J., Girijavallabhan V., Kirschmeier P. and Bishop W.
Cancer Research. 1998, 58(21): 4947-56.

Epoxybutene-Hemoglobin Adducts In Rats And Mice: Dose Response For Formation And Persistence During And Following Long-Term Low-Level Exposure To Butadiene.
Osterman-Golkar S., Moss O., James A., Bryant M., Turner M. and Bond J.
Toxicol. Applied Pharmacol. 1998, 150(1): 166-173.

Pharmacokinetic Screening for Selection of New Drug Discovery Candidates is Greatly Enhanced through the Use of LC-API/MS/MS.
Bryant M., Korfmacher W., Wang S., Nardo C., Nomeir A. and Lin C.
Journal of Chromatography A. 1997, 777(1): 61-66.

2,6-Dimethylaniline-Hemoglobin Adducts From Lidocaine in Humans.
Bryant M., Simmons H., Harrell R. and Hinson J.
Carcinogenesis. 1994, 15: 2287-90.

Detection and Characterization of DNA Adducts at the Femtomole Level by Desorptive Ionization Mass Spectrometry.
Lay J., Chiarelli M., Bryant M. and Nelson R.
Environmental Health Perspectives. 1993, 99: 191-3.

Development of Fast Atom Bombardment Mass Spectral Methods for the Identification of Carcinogen Nucleoside Adducts.
Bryant M., Chiarelli P. and Lay J.
J. Amer. Soc. Mass Spectrom. 1992, 3: 360-371.

Decline of the Hemoglobin Adduct of 4 Aminobiphenyl during Withdrawal from Smoking.
Maclure M., Bryant M., Hankinson S., Skipper P. and Tannenbaum S.
Cancer Research. 1990, 50: 181 4.

Elevated Blood Levels of Carcinogens in Passive Smokers.
Maclure M., Abraham B., Katz R., Bryant M., Skipper P. and Tannenbaum S.
American Journal of Public Health. 1989, 79: 1381 4.

Hemoglobin Adducts of Aromatic Amines: Associations with Smoking Status and Type of Tobacco.
Bryant M., Vineis P., Skipper P. and Tannenbaum S.
Proceedings of the National Academy of Sciences U.S.A. 1988, 85: 9788 91.

Hemoglobin Adducts of 4 Aminobiphenyl in Smokers and Nonsmokers.
Bryant M., Skipper P., Tannenbaum S. and Maclure M.
Cancer Research. 1987, 47: 602 608.

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