An IVRT method was developed and validated to confirm its reproducibility, precision, sensitivity, selectivity, accuracy, robustness, and reliability. A novel approach was used to demonstrate the appropriateness of the IVRT method to accurately assess "sameness" between topical products and to confirm that the methodology applied also possesses the requisite discriminatory power to detect differences should such differences exist between products. In the first instance, the reference product (Metrocreme) containing 0.75% metronidazole (MTZ) was tested against itself as a positive control, to accurately demonstrate "sameness", where the results met the relevant acceptance criteria falling within the limits of 75-133.33% in accordance with the FDA's SUPAC-SS guidance. In addition, two specially prepared creams containing 25% less and 26% more MTZ, i.e., 0.563% and 0.945%, served as negative controls and were compared against the reference product. Neither of these creams fell within the "sameness" acceptance criteria, thereby confirming the discriminatory ability of the IVRT method to detect differences between MTZ products. Furthermore, another cream containing 0.75% MTZ tested against the reference product was shown to be pharmaceutically equivalent to the reference product. These results confirm the appropriateness of the IVRT method as a valuable tool for use in the development of topical MTZ products intended for local action and indicate the potential for general use with other topical products.