Stability-Indicating RP-HPLC Determination of Acetylsalicylic Acid, Dextromethorphan Hydrobromide, Phenylephrine Bitartrate, and Chlorpheniramine Maleate in an Effervescent Tablet Formulation.

BACKGROUND

Multi-component effervescent tablets containing acetylsalicylic acid (ASA), dextromethorphan hydrobromide (DMH), phenylephrine bitartrate (PB), and chlorpheniramine maleate (CPM) pose analytical challenges due to their complex excipient composition and moisture sensitivity. Accurate quantification of these active pharmaceutical ingredients and their related degradation products or impurities is essential for product quality and stability evaluation.

OBJECTIVE

To develop and validate a stability-indicating reversed-phase HPLC (RP-HPLC) method for the determination of ASA, DMH, PB, CPM in an effervescent tablet formulation, together with the monitoring of selected related impurities.

METHODS

Chromatographic separation was achieved on an InertSustain C8 column (150 × 4.6 mm, 5 µm) using a phosphate buffer-methanol gradient containing sodium heptane sulfonate at pH 2.0, with dual-wavelength detection at 215 and 304 nm. The method was validated per ICH Q2(R2) for specificity, linearity, accuracy, precision, and solution stability. Forced degradation studies under acid, base, oxidative, photolytic, and thermal conditions confirmed stability-indicating capability.

RESULTS

The method provided baseline resolution of all analytes within a single chromatographic program. Linearity (R² > 0.998 for APIs, > 0.993 for impurities), recoveries (98-102% for APIs, 90-110% for impurities), and precision (%RSD ≤ 2.0 for APIs, ≤ 5.0 for impurities) met acceptance criteria.

CONCLUSION

The developed RP-HPLC method demonstrated reliable performance and can be applied for routine quality control and stability testing of the evaluated effervescent tablet formulation containing multiple active ingredients.

HIGHLIGHTS: This method employs ion-pairing at pH 2.0 optimized for the effervescent matrix and dual-wavelength detection for the quantification of actives and selected impurities. Fully validated per ICH Q2(R2), it demonstrates a clear stability-indicating capability and suitability for QC and stability studies of the evaluated effervescent tablet formulation.