Stability-Indicating Spectrophotometric and TLC Densitometric Validated Methods for Simultaneous Assay of Salicylamide and Ascorbic Acid in the Presence of Salicylic Acid: Greenness Assessment and Practical Applicability

Objectives: Three stability-indicating analytical methods featuring outstanding sensitivity, selectivity, and precision were set up for the quantification of salicylamide (SAD) and ascorbic acid (ASC) in the presence of salicylic acid (SAL), which represents a possible impurity and degradation product of SAD. The aim was to develop sensitive, selective, precise, and eco-friendly assays appropriate for routine quality control of pharmaceuticals. Methods: Method (A) was a spectrophotometric technique of a successive derivative of ratio spectra built upon a two-step derivatization of ratio spectra utilizing double-distilled water as a solvent. SAD was quantified at 247.2 nm and 257.0 nm, and ASC at 251.8 and 259.8 nm, while SAL was quantified at 305.6 nm. Technique (B) relied on ratio spectra for the mean centering analytical process applied via two sequential stages, where the amplitudes derived after the second ratio spectra of the mean centering have been recorded on 291.0, 266.0, and 241.0 nm for SAD, ASC, and SAL, in that order. Method (C) involved TLC densitometric analysis, in which the separation was carried out upon plates of silica gel with chloroform–hexane–methanol–acetone–formic acid (5:3:2:1:0.2, in volumes) as a mobile phase, monitored by densitometric detection at 240 nm. The linear relationships were observed over concentration ranges of (0.2–2 µg/band) for SAD with ASC and (0.1–1 µg/band) for SAL. Validation of the presented techniques was performed in accordance with ICH strategies. Results: These developed techniques have been effectively analyzed for SAD with ASC in pharmaceutical dosage forms with non-interfering ingredients. A statistical comparison with the previously used HPLC technique revealed no considerable difference in terms of accuracy and precision. Greenness assessment using the AGREE platform produced scores of 0.72 for the spectrophotometric approach (benefiting from aqueous solvent) and 0.62 for HPTLC (limited by chloroform). Practical applicability (BAGI = 80 for both spectrophotometry and HPTLC) and overall quality indices (CACI = 83 for spectrophotometry; 80 for HPTLC) supported routine QC suitability. Conclusions: The three developed stability-indicating methods are accurate, precise, and selective for simultaneous assay of SAD and ASC in the presence of SAL and are suitable for quality control use. The spectrophotometric procedures combine high analytical performance with an improved environmental profile, while HPTLC offers comparable analytical reliability with slightly lower greenness due to organic solvent use.