Stability-Indicating RP-HPLC Determination of Acetylsalicylic Acid, Dextromethorphan Hydrobromide, Phenylephrine Bitartrate, and Chlorpheniramine Maleate in an Effervescent Tablet Formulation
Abstract
Background: Multicomponent 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, and 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 in accordance with 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% for APIs, ≤5% for impurities) met acceptance criteria.
Conclusions: 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 optimized for the effervescent matrix and dual-wavelength detection for the quantification of actives and selected impurities. Fully validated in accordance with ICH Q2 (R2), it demonstrates a clear stability-indicating capability and suitability for QC and stability studies of the evaluated effervescent tablet formulation.
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BibTeX
@article{atlı2026stabilityindicating,
title = {{Stability-Indicating RP-HPLC Determination of Acetylsalicylic Acid, Dextromethorphan Hydrobromide, Phenylephrine Bitartrate, and Chlorpheniramine Maleate in an Effervescent Tablet Formulation}},
author = {Selin Atlı and Özlem Aksu Dönmez},
journal = {Journal of AOAC International},
year = {2026},
month = aug,
doi = {10.1093/jaoacint/qsag070},
url = {https://doi.org/10.1093/jaoacint/qsag070},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Stability-Indicating RP-HPLC Determination of Acetylsalicylic Acid, Dextromethorphan Hydrobromide, Phenylephrine Bitartrate, and Chlorpheniramine Maleate in an Effervescent Tablet Formulation
AU - Selin Atlı
AU - Özlem Aksu Dönmez
PY - 2026
DA - 2026/08/07
JO - Journal of AOAC International
DO - 10.1093/jaoacint/qsag070
UR - https://doi.org/10.1093/jaoacint/qsag070
AB - Background: Multicomponent 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, and 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 in accordance with 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% for APIs, ≤5% for impurities) met acceptance criteria. Conclusions: 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 optimized for the effervescent matrix and dual-wavelength detection for the quantification of actives and selected impurities. Fully validated in accordance with ICH Q2 (R2), it demonstrates a clear stability-indicating capability and suitability for QC and stability studies of the evaluated effervescent tablet formulation.
SN - 1060-3271
SN - 1944-7922
ER -