ICRF-assisted Box-Behnken design and optimization for rapid UPLC-PDA determination of dorzolamide hydrochloride and timolol maleate in an ophthalmic preparation
JOURNAL OF AOAC INTERNATIONAL, 2026 (SCI-Expanded, Scopus)
- Yayın Türü: Makale / Tam Makale
- Basım Tarihi: 2026
- Doi Numarası: 10.1093/jaoacint/qsag060
- Dergi Adı: JOURNAL OF AOAC INTERNATIONAL
- Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, BIOSIS, Chemical Abstracts Core, Chimica, Compendex, EMBASE, Food Science & Technology Abstracts, MEDLINE, DIALNET, Zoological Record, Academic Search Ultimate (EBSCO), Biomedical Reference Collection: Corporate Edition (EBSCO), Engineering Source (EBSCO)
- Gazi Üniversitesi Adresli: Evet
Özet
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. Objective 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. Methods 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. Results 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 & times; 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 & micro;g/mL (r > 0.999), with LODs of 0.51 & micro;g/mL for DH and 0.61 & micro;g/mL for TI. Mean recoveries were 99.9% and 99.5% for DH and TI, respectively, with satisfactory precision and robustness. Conclusion 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.Highlights The study demonstrates the effectiveness of composite response-based chemometric optimization in enhancing analytical efficiency in pharmaceutical drug analysis.