Determination of Impurities in Pharmaceuticals

Importance of the topic

Pharmaceutical quality control requires reliable detection of trace impurities in active drug substances to ensure safety and efficacy. Famotidine, a widely used histamine‐2 receptor antagonist, must meet stringent pharmacopoeial standards. Implementing a robust analytical method for impurity profiling supports regulatory compliance and safeguards patient health.

Study objectives and overview

This application note describes the development of a reversed‐phase HPLC procedure for quantifying famotidine and related impurities. The aim was to achieve baseline separation, adequate sensitivity, and reproducible retention, in line with Japanese Pharmacopoeia (JP) requirements.

Methodology and instrumentation

The following setup was employed:

• Column: Shim‐pack™ VP‐ODS, 150 mm × 4.6 mm I.D., 5 µm
• Mobile phase: 2 g sodium 1‐heptane sulfonate in 900 mL water, pH 3.0 (acetic acid), diluted to 1000 mL; mixed with 240 mL acetonitrile and 40 mL methanol
• Flow rate: 0.45 mL/min, adjusted to yield a ~6 min retention for famotidine
• Column temperature: 25 °C
• Detector: SPD‐M20A UV at 254 nm
• Injection volume: 5 µL

Main results and discussion

The method provided sharp, symmetric peaks for famotidine and its impurities, with consistent retention time and minimal baseline noise. Selectivity was sufficient to resolve all targets within a reasonable run time. System suitability tests confirmed reproducibility of retention times and peak areas.

Benefits and practical applications

• Compliance with JP impurity guidelines
• High reproducibility and routine operation stability
• Compatibility with standard HPLC equipment in QC laboratories

Future trends and potential uses

Further enhancements may include adoption of ultrahigh‐pressure LC for faster throughput, integration with mass spectrometric detection for structural elucidation of unknown impurities, and exploration of greener solvent systems to reduce environmental impact.

Conclusion

The described HPLC method using Shim‐pack VP‐ODS and a carefully optimized mobile phase delivers a reliable, easy‐to‐implement solution for routine quality control of famotidine impurities.

Reference

Application News L461, Shimadzu Corporation, First Edition: Dec. 2021