Reliable HPLC Method for the Simultaneous Determination of Aspirin and Associated Related Substances in Drug Substance and Tablet Formulation

Importance of the Topic

Aspirin is a cornerstone of analgesic and cardiovascular therapies, necessitating rigorous quality control under current Good Manufacturing Practices. A single analytical method capable of simultaneously quantifying aspirin and its related impurities enhances efficiency and compliance in pharmaceutical testing.

Objectives and Study Overview

This study aimed to develop and validate a robust HPLC method for the simultaneous determination of aspirin API and six associated related substances in both drug substance and tablet formulations, meeting USP and pharmacopoeial criteria.

Methodology

Standard solutions of aspirin and impurities were prepared in 60:40 water/acetonitrile with 0.1% formic acid, with working concentrations of 0.1 mg/mL for aspirin assay and 0.5 mg/mL for impurity profiling. Tablets (81 mg aspirin) were extracted by sonication, centrifuged and filtered. Chromatographic separation was achieved on an XSelect HSS T3 column with UV detection at 237 nm under isocratic conditions.

Instrumentation

• Alliance iS HPLC system
• Waters XSelect HSS T3 column

Main Results and Discussion

The developed method delivered high resolution (USP Rs ≥ 4.9), low peak tailing (1.1–1.2) and satisfactory retention (k* ≥ 2.1). Linearity for aspirin in the 80–120% range yielded R² ≥ 0.999, with deviations between –0.35% and 0.81%. Intraday and interday precisions showed RSD ≤ 0.25% for peak areas and ≤ 0.03% for retention times. Tablet assay results ranged from 93.4% to 93.6%, complying with USP limits (90.0–110.0%). Related substances were quantified within specified thresholds (salicylic acid NMT 0.3%, other impurities per monograph).

Benefits and Practical Applications

This single-run HPLC method streamlines quality control workflows by simultaneously monitoring the API and multiple impurities, reducing analysis time and resource consumption while ensuring regulatory compliance.

Future Trends and Potential Applications

Advancements may include extension to other NSAIDs, coupling with mass spectrometry for enhanced sensitivity, and adaptation to ultra-high-performance liquid chromatography to further shorten run times and increase throughput.

Conclusion

The validated HPLC procedure provides a reliable, precise and compliant approach for comprehensive aspirin analysis in pharmaceutical substances and products, supporting robust quality assurance.

References

• European Pharmacopoeia 10.0. Monograph: Acetylsalicylic Acid. 01/2017:0309
• United States Pharmacopeia USP43–NF38. Monograph: Aspirin Tablets. Official May 1, 2020.