Development of a HPLC fluorometric method for the quantification of enfuvirtide following in vitro releasing studies on thermosensitive in situ forming gel.

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  • Additional Information
    • Source:
      Publisher: Springer Country of Publication: United States NLM ID: 101540061 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2190-3948 (Electronic) Linking ISSN: 2190393X NLM ISO Abbreviation: Drug Deliv Transl Res Subsets: MEDLINE
    • Publication Information:
      Original Publication: New York : Springer
    • Subject Terms:
      Peptide Fragments*/chemistry ; HIV Fusion Inhibitors*/therapeutic use; Enfuvirtide ; Chromatography, High Pressure Liquid/methods ; HIV Envelope Protein gp41/chemistry ; Pharmaceutical Preparations
    • Abstract:
      Due to the presence of peptidase and protease in the gastrointestinal tract, peptides are subjected to digestion and inactivation when administrated orally. To avoid degradation and maintain the desired efficacy of peptide drugs, there is a demand to develop transdermal and intradermal delivery systems. This requires efficient and specific analytical methods to separate and quantify the peptide drugs from the formulation and the skin matrix in the early stages of pharmaceutical development. A high-performance liquid chromatography (HPLC) system equipped with a fluorometric detector was used to quantify enfuvirtide, which is the first fusion inhibitor for HIV treatment. The HPLC method was developed and validated according to the ICH Q2(R1) guidelines. The viability of the method was demonstrated during in vitro studies, where samples were analysed following intradermal administration of a thermosensitive in situ forming gel. Compared with previously reported methods, this assay proved efficient, sensitive and accurate, with a detection limit of 0.74 μg/mL and a run time of 9 min, mitigating the use of any internal standards and detergents. The addition of an organic solvent to the samples successfully solved the problem of low recovery caused by the adsorption of the drug to the plastic consumables in the sample treatment process. The amount of enfuvirtide releasing from the in situ gel through skin after 7 hours was 16.25 ± 7.08 μg, which was significantly lower than the reconstituted FUZEON ® itself (26.68 ± 10.45 μg), showing a longer release profile. The results may be beneficial as a constructive input for future enfuvirtide quantification within a preclinical setting through in vitro release studies across the skin.
      (© 2023. The Author(s).)
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    • Contributed Indexing:
      Keywords: Enfuvirtide; Fluorescence detector; HPLC; Intradermal delivery; Peptide
    • Accession Number:
      19OWO1T3ZE (Enfuvirtide)
      0 (Peptide Fragments)
      0 (HIV Envelope Protein gp41)
      0 (HIV Fusion Inhibitors)
      0 (Pharmaceutical Preparations)
    • Publication Date:
      Date Created: 20230429 Date Completed: 20230704 Latest Revision: 20230705
    • Publication Date:
      20240829
    • Accession Number:
      PMC10315353
    • Accession Number:
      10.1007/s13346-023-01344-5
    • Accession Number:
      37120679