Abstract
Background
Determination of different drugs in the presence of their impurities is now receiving attention from regulatory authorities such as the ICH and the United States Food and Drug Administration (USFDA).
Objective
To develop and validate a reversed-phase (RP)-HPLC method for the simultaneous separation and quantification of a quaternary mixture of propyphenazone, flavoxate HCl, and their official impurities; phenazone and 3-methylflavone-8-carboxylic acid, respectively. Then utilize the validated method as an in vitro methodology to monitor the rate of release of the active ingredients from Cistalgan® tablets.
Methods
RP-HPLC method was applied using Kinetex® coreshell C8 column (250 mm × 4.6 mm I.D., particle size 5 μm) and acetonitrile: phosphate buffer pH 3.50 (42:58, v/v) as the mobile phase with UV detection at 240.0 nm.
Results
The studied components were eluted with average retention times of 2.80, 3.40, 4.20, and 5.90 min for phenazone, flavoxate HCl, 3-methylflavone-8-carboxylic acid, and propyphenazone, respectively within linearity range of 1.00–60.00 µg/mL propyphenazone, 3.00–60.00 µg/mL flavoxate HCl and 0.50–40.00 µg/mL of the specified impurities.
Conclusions
The suggested method could be considered as the first validated analytical method for the simultaneous determination of the studied components and proved to be accurate, precise, sensitive, and robust.
Highlights
The proposed method displays a useful analytical tool for dissolution profiling and clear discrimination of both active ingredients from their impurities along with impurities profiling.
RP-HPLC Method for the Simultaneous Determination of a Quaternary Mixture of Propyphenazone, Flavoxate HCl and Two of Their Official Impurities with Dissolution Profiling of Their Tablets