{
  "abstract": "Background: Simultaneous optimization of chromatographic resolution and analysis time constitutes a significant analytical challenge in multicomponent pharmaceutical analysis, as resolution-driven optimization strategies may improve peak separation without providing explicit control over retention time, often resulting in unnecessarily prolonged runtimes. To address this limitation, an optimization strategy based on a Box–Behnken experimental design was implemented in conjunction with the improved chromatographic response function (ICRF), which integrates separation quality and analysis time within a single mathematical objective function.\n\nObjective: This strategy describes the development of a rapid, chemometrically optimized Ultra Performance Liquid Chromatography coupled with a Photodiode Array Detector (UPLC–PDA) method for the simultaneous determination of dorzolamide hydrochloride (DH) and timolol maleate (TI) in a commercial ophthalmic preparation.\n\nMethods: A Box–Behnken experimental design and optimization approach was employed in combination with an ICRF, which integrates resolution, peak overlap, peak width, and runtime into a single composite objective function. This strategy enabled short runtime (or short retention time of analytes in a chromatogram) while preserving adequate peak separation.\n\nResults: Under the optimized conditions, complete chromatographic separation was achieved within 3 min using a BEH C18 column and a mobile phase consisting of acetonitrile–4 × 10−4 M CCl3COOH (60 + 40, v/v) at a flow rate of 0.32 mL/min with detection at 275 nm. The method demonstrated excellent linearity over the range of 5.0–40.0 µg/mL (r > 0.999), with LODs of 0.51 µg/mL for DH and 0.61 µg/mL for TI. Mean recoveries were 99.9% and 99.5% for DH and TI, respectively, with satisfactory precision and robustness.\n\nConclusion: The proposed ICRF-assisted optimization approach provided high-resolution separation within minimal runtime and was successfully applied to the routine QC analysis of a commercial ophthalmic formulation.\n\nHighlights: The study demonstrates the effectiveness of composite response-based chemometric optimization in enhancing analytical efficiency in pharmaceutical drug analysis.",
  "abstract_shown": true,
  "affiliations": [],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 2,
  "authors": [
    {
      "name": "Erdal Dinç",
      "orcid": "0000-0001-6326-1441"
    },
    {
      "name": "Eda Büker"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/23b481vg8gtkh.bib",
  "cited_by": 0,
  "doi": "10.1093/jaoacint/qsag060",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13732700/",
  "id": "23b481vg8gtkh",
  "issns": [
    "1060-3271",
    "1944-7922"
  ],
  "landing_url": "https://doi.org/10.1093/jaoacint/qsag060",
  "language": "en",
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "AcademicSubjects/SCI00010"
    ],
    [
      "heading",
      "Drug Formulations"
    ],
    [
      "heading",
      "Research Article"
    ],
    [
      "openalex",
      "1602|Analytical Methods in Pharmaceuticals"
    ]
  ],
  "openalex": "W7165866745",
  "pdf_url": null,
  "pmcid": "PMC13732700",
  "pmid": "42348236",
  "published": "2026-06-25",
  "publisher": "Oxford University Press",
  "ris": "https://research.draconitic.com/paper/23b481vg8gtkh.ris",
  "sources": [
    {
      "first_seen": "2026-11-08T12:22:38Z",
      "native_id": "PMC13732700",
      "source": "pmc",
      "url": "https://doi.org/10.1093/jaoacint/qsag060"
    }
  ],
  "subjects": [
    {
      "field": "chemistry",
      "origin": "openalex:1602|Analytical Methods in Pharmaceuticals",
      "subfield": "analytical"
    }
  ],
  "title": "ICRF-assisted Box–Behnken design and optimization for rapid UPLC–PDA determination of dorzolamide hydrochloride and timolol maleate in an ophthalmic preparation",
  "title_text": "ICRF-assisted Box–Behnken design and optimization for rapid UPLC–PDA determination of dorzolamide hydrochloride and timolol maleate in an ophthalmic preparation",
  "type": "peer-reviewed",
  "updated_at": "2026-11-08T12:22:38Z",
  "url": "https://research.draconitic.com/paper/23b481vg8gtkh",
  "venue": "Journal of AOAC International",
  "versions": []
}