Contents

Paired Assay Balance and Green Derivative UV Quantification of Brinzolamide–Timolol Ophthalmic Products

Author(s): Peter W. Carr1, Malcolm Nicoll1, Robert Freeman2
1Professor of Chemistry, University of Minnesota
2Department of Chemistry, Faculty of Science, Sakarya Applied Sciences University, Sakarya, Türkiye
Peter W. Carr
Professor of Chemistry, University of Minnesota
Malcolm Nicoll
Professor of Chemistry, University of Minnesota
Robert Freeman
Department of Chemistry, Faculty of Science, Sakarya Applied Sciences University, Sakarya, Türkiye

Abstract

Fixed dose ophthalmic pharmaceuticals made up of brinzolamide (BRZ) and timolol maleate (TML) must be characterized through an analysis which enables quantitative determination of both substances in a single mixture without depending on the use of solvent for routine product quality control. In this case, the present paper will assess if the first order derivative UV-spectrophotometric method could provide adequate basis for making decisions concerning the quality control of BRZ-TML products taking into consideration their calibration margin, recovery, balance of formulation, and environmental cost. Analytical data included derivative wavelengths 248.80 nm and 297.60 nm for BRZ and TML respectively; calibration interval range 4-24 and 5-25 μg mL-1; detection and quantification limits; 6 triplicate recovery series; assay values of three commercially available formulations and one in situ gel; as well as greenness values from AGREE, eco-scale, and penalty point calculations. Linearity coefficients of R2=0.9998 and R2=0.9999 were determined in the case of BRZ and TML respectively. Quantification limits of 0.91 μg mL-1 (BRZ) and 2.99 μg mL-1 (TML) were found, corresponding to a sensitivity ratio of 4.40 and 1.67 against the first calibration point. Recoveries varied between 97.43-103.22% (BRZ) and 101.73-103.34% (TML), where all relative standard deviations were under 2%. Assay values of the test products ranged between 102.63-105.39% for BRZ and 102.52-105.68% for TML. An in situ gel preparation gave the most balanced paired assay with only 0.03 percentage point difference between BRZ and TML. The derivative UV method further yielded AGREE score 0.77, eco-scale score 88, and 12 penalty points reflecting its low environmental impact as compared to its competitor, the chromatographic method.

Keywords: brinzolamide; timolol maleate; derivative UV spectrophotometry; paired assay; green analytical chemistry; ophthalmic suspension; analytical validation
Copyright © 2024 Peter W. Carr, Malcolm Nicoll, Robert Freeman. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.