Stability indicating multipurpose HPLC-DAD method for synchronic analysis of three non-steroidal anti-inflammatory drugs with a co-formulated preservative in ophthalmic dosage forms - Greenness/whiteness assessment

Abstract

This research presents a validated, multipurpose and sustainable HPLC-DAD method intended for the separation and simultaneous determination of three related non-steroidal ant-inflammatory drugs (NSAIDs): diclofenac sodium, bromfenac sodium and nepafenac in the presence of five of their related compounds and suspected impurities. A Venusil XBP Cyano column with gradient elution of a mobile phase involving methanol, acetonitrile and mixed phosphate and sodium pentane sulfonate buffer (pH 2.5) were employed. DAD was tuned at 210, 233 and 275 nm for measuring peak areas of different analytes. The proposed procedure was successfully validated and utilized in comprehensive stability study of the investigated drugs. The three NSAIDs have been determined within a linearity range of 5–150 µg/mL with excellent analytical performance. The method targeted their analysis in variable dosage forms particularly ophthalmic liquid preparations. This has evolved the need to determine benzalkonium chloride as well which is a common preservative in such dosage forms. It was measured in the range 10–200 µg/mL. The least detectable concentration levels of the analytes were within the range 0.5–2.0 µg/mL. Comparing the designed method to a number of reported ones with respect to greenness and whiteness/sustainability merits using AGREE and RGB-12 paradigms proved it is significantly eco-friendly and represents a green/white option for multi-analyte stability indicating analysis of the above-mentioned drugs.