Reliable HPLC Analysis of Aspirin and Associated Related Substances in Drug Substance and Tablet Formulation

Importance of the Topic

Ensuring the quality and purity of aspirin drug products is critical for patient safety and regulatory compliance under current CGMP guidelines.
A unified HPLC method for simultaneous assay and impurity profiling streamlines quality control in both active pharmaceutical ingredients and finished tablet formulations.

Objectives and Study Overview

This study presents a single high-performance liquid chromatography (HPLC) approach to quantify aspirin and its six related substances in raw API and 81-mg tablet dosage forms.
Key goals include demonstrating system suitability, method linearity, accuracy, precision, and impurity determination conforming to European Pharmacopeia and USP standards.

Methodology and Instrumentation

Standard and sample preparations:

• Aspirin API and six impurities prepared in 60:40 water/acetonitrile with 0.1% formic acid at specified concentrations.
• Tablet samples dissolved, sonicated, centrifuged, and filtered to 0.1 mg/mL for assay and 0.5 mg/mL for impurity analysis.

Instrumental conditions:

• HPLC system: Alliance iS with TUV detector.
• Column: XSelect HSS T3 (4.6×150 mm, 3.5 μm) at 40 °C.
• Mobile phase A: 0.1% formic acid in water; B: 0.1% formic acid in acetonitrile; flow rate 1.8 mL/min with gradient elution.
• Detection wavelength: 237 nm; injection volume: 15 μL; sample temperature: 10 °C.

Key Results and Discussion

Separation and system suitability:

• Complete separation of aspirin and six impurities in 7.6 min with USP resolution ≥4.8, tailing factor 1.0–1.2, and retention factor ≥2.1.
• System suitability met USP criteria: RSD of peak areas ≤0.25%, RSD of retention times ≤0.03%, and resolution ≥5.3.

Linearity and accuracy:

• Aspirin calibration (80–120% of 0.1 mg/mL) yielded R² ≥0.999 with concentration deviations between –0.35% and 0.81%.
• Tablet assay results (n=6) ranged from 93.4% to 93.6% recovery, within USP limits of 90.0–110.0%.

Impurity profiling:

• Tablet samples contained salicylic acid (impurity C) at 0.91% and impurity D at 0.05%; API showed impurity C at 0.15%.
• Results complied with USP impurity limits: ≤3.0% for coated tablets and ≤0.3% for API.

Benefits and Practical Applications

• Single analytical method reduces analysis time and resource expenditure.
• High sensitivity and precision support rigorous quality control in pharmaceutical manufacturing.
• Applicable for routine batch release testing of both API and tablet formulations.

Future Trends and Opportunities

Advances in detection technology and column materials may further shorten run times and enhance impurity resolution.
Integration with automated data processing and laboratory information management systems will increase throughput and compliance robustness.

Conclusion

The developed HPLC method on the Alliance iS system offers rapid, accurate, and reproducible assay and impurity analysis for aspirin API and tablets, fully meeting compendial requirements.

References

1. European Pharmacopeia Monograph 10.0: Acetylsalicylic Acid, 01/2017:0309.
2. United States Pharmacopeia USP43-NF38: Aspirin Tablets monograph, official 01-May-2020.