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Chiral HPLC analysis of donepezil, 5-O-desmethyl donepezil and 6-O-desmethyl donepezil in culture medium: application to fungal biotransformation studies

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Abstract

An high performance liquid chromatography (HPLC) method for the enantioselective determination of donepezil (DPZ), 5-O-desmethyl donepezil (5-ODD), and 6-O-desmethyl donepezil (6-ODD) in Czapek culture medium to be applied to biotransformation studies with fungi is described for the first time. The HPLC analysis was carried out using a Chiralpak AD-H column with hexane/ethanol/methanol (75:20:5, v/v/v) plus 0.3 % triethylamine as mobile phase and UV detection at 270 nm. Sample preparation was carried out by liquid–liquid extraction using ethyl acetate as extractor solvent. The method was linear over the concentration range of 100–10,000 ng mL−1 for each enantiomer of DPZ (r ≥ 0.9985) and of 100–5,000 ng mL−1 for each enantiomer of 5-ODD (r ≥ 0.9977) and 6-ODD (r ≥ 0.9951). Within-day and between-day precision and accuracy evaluated by relative standard deviations and relative errors, respectively, were lower than 15 % for all analytes. The validated method was used to assess DPZ biotransformation by the fungi Beauveria bassiana American Type Culture Collection (ATCC) 7159 and Cunninghamella elegans ATCC 10028B. Using the fungus B. bassiana ATCC 7159, a predominant formation of (R)-5-ODD was observed while for the fungus C. elegans ATCC 10028B, DPZ was biotransformed to (R)-6-ODD with an enantiomeric excess of 100 %.

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Acknowledgments

The authors are grateful to Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP), Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), and Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) for financial support and for granting research fellowships.

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The authors have declared no conflict of interest.

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Authors and Affiliations

  1. Departamento de Física e Química, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Av. Café SN, Ribeirão Preto, SP, 14040-903, Brazil

    Thiago Barth & Pierina Sueli Bonato

  2. Departamento de Ciências Farmacêuticas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, 14040-903, Brazil

    Raphael Conti & Mônica Tallarico Pupo

  3. Departamento de Química, Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, 14040-901, Brazil

    Laura Tiemi Okano

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  1. Thiago Barth
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  2. Raphael Conti
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  3. Mônica Tallarico Pupo
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  4. Laura Tiemi Okano
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  5. Pierina Sueli Bonato
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Correspondence to Thiago Barth or Pierina Sueli Bonato.

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Barth, T., Conti, R., Pupo, M.T. et al. Chiral HPLC analysis of donepezil, 5-O-desmethyl donepezil and 6-O-desmethyl donepezil in culture medium: application to fungal biotransformation studies. Anal Bioanal Chem 404, 257–266 (2012). https://doi.org/10.1007/s00216-012-6107-3

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  • DOI: https://doi.org/10.1007/s00216-012-6107-3

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