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Research Article

Quantification of phenolic acid metabolites in humans by LC–MS: a structural and targeted metabolomics approach

    Mark E Obrenovich

    Pathology & Laboratory Medicine Service, Louis Stokes Cleveland Department of Veteran's Affairs Medical Center, Cleveland, OH, 44106, USA

    Research Service, Louis Stokes Cleveland Department of Veterans Affairs Medical Center, Cleveland, OH, 44106, USA

    Department of Chemistry, Case Western Reserve University, Cleveland, OH, 44106, USA

    Department of Medicinal & Biological Chemistry, College of Pharmacy & Pharmaceutical Sciences, University of Toledo, Toledo, OH, 43614, USA

    ,
    Curtis J Donskey

    Infectious Disease Service, Louis Stokes Cleveland Department of Veterans Affairs Medical Center, Cleveland, OH, 44106, USA

    School of Medicine, Case Western Reserve University, Cleveland, OH, 44106, USA

    ,
    Isaac T Schiefer

    Department of Medicinal & Biological Chemistry, College of Pharmacy & Pharmaceutical Sciences, University of Toledo, Toledo, OH, 43614, USA

    ,
    Rodolfo Bongiovanni

    Research Service, Louis Stokes Cleveland Department of Veterans Affairs Medical Center, Cleveland, OH, 44106, USA

    ,
    Ling Li

    Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH, 44106, USA

    &
    George E Jaskiw

    *Author for correspondence:

    E-mail Address: gxj5@case.edu

    Psychiatry Service, Louis Stokes Cleveland Department of Veterans Affairs Medical Center, Cleveland, OH, 44106, USA

    Department of Psychiatry, Case Western Reserve University, Cleveland, OH, 44106, USA

    Published Online:https://doi.org/10.4155/bio-2018-0140

    Aim: Co-metabolism between a human host and the gastrointestinal microbiota generates many small phenolic molecules such as 3-hydroxy-3-(3-hydroxyphenyl)propanoic acid (3,3-HPHPA), which are reported to be elevated in schizophrenia and autism. Characterization of these chemicals, however, has been limited by analytic challenges. Methodology/results: We applied HPLC to separate and quantify over 50 analytes, including multiple structural isomers of 3,3-HPHPA in human cerebrospinal fluid, serum and urine. Confirmation of identity was provided by NMR, by MS and other detection methods. The highly selective methods support rapid quantification of multiple metabolites and exhibit superior chromatographic behavior. Conclusion: An improved ultra-HPLC–MS/MS and structural approaches can accurately quantify 3,3-HPHPA and related analytes in human biological matrices.

    Papers of special note have been highlighted as: • of interest; •• of considerable interest

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