SIMULTANEOUS DETERMINATION OF NAPHAZOLINE HYDROCHLORIDE AND PHENIRAMINE MALEATE ALONG WITH THEIR RELATED COMPOUNDS BY HIGH PERFORMANCE LIQUID CHROMATOGRAPHY

Importance of the Topic

Simultaneous analysis of multiple active pharmaceutical ingredients (APIs) and their impurities within a single high-performance liquid chromatography (HPLC) method addresses regulatory demands for updated compendial procedures and environmental concerns by reducing hazardous solvent usage and laboratory waste.

Objectives and Study Overview

This work aimed to consolidate three separate United States Pharmacopeia (USP) monograph methods for naphazoline hydrochloride and pheniramine maleate into a unified HPLC procedure capable of quantifying both APIs and their related compounds in ophthalmic and nasal formulations.

Methodology

Samples of APIs and impurities were sourced from USP. Standard solutions containing 500 µg/mL pheniramine maleate, 40 µg/mL naphazoline HCl, and 5 µg/mL related substances were prepared in a 90:10 water:acetonitrile diluent. An Alliance iS HPLC system with a tunable UV detector operating at 260 nm was employed. Chromatographic separation used an XSelect CSH C18 column (5 µm, 4.6×150 mm) at 40 °C with a gradient from 5% to 95% organic modifier over 7 minutes, a flow rate of 2.0 mL/min, 8 µL injection volume, and a sample temperature of 5 °C.

Instrumentation

An Alliance iS HPLC system equipped with a tunable UV detector (wavelengths 260 and 280 nm) and an XSelect CSH C18 column was used.

Main Results and Discussion

System suitability testing with 12 replicate injections yielded relative standard deviations below 0.1% for peak areas and below 0.2% for retention times. Linearity assessments across 80%–120% concentration ranges showed correlation coefficients (R2) exceeding 0.997 for both APIs. USP resolution criteria were met with minimum resolution values above 2.4 for all analyte pairs. Intra-day and inter-day precision studies confirmed method robustness with RSD values well within compendial limits. Application to six commercial ophthalmic and nasal products demonstrated accurate quantification of naphazoline, pheniramine, and their impurities.

Benefits and Practical Applications

• Consolidates multiple USP monographs into a single analytical method.
• Minimizes solvent consumption and hazardous waste generation.
• Ensures robust performance with high precision, accuracy, and resolution.
• Applicable to quality control of ophthalmic and nasal formulations.

Future Trends and Potential Applications

Future work may extend this approach to additional multi-API products, integrate greener solvents or ultra-high-pressure LC (UHPLC) technologies, and adapt the method for inline process monitoring in pharmaceutical manufacturing.

Conclusion

The developed HPLC method provides a streamlined, environmentally conscious, and fully validated procedure for the simultaneous determination of naphazoline hydrochloride, pheniramine maleate, and their related compounds, supporting modernized compendial standards and routine quality control.

References

• USP Monograph, Naphazoline Hydrochloride Nasal Solution, USP40-NF35, The United States Pharmacopeia Convention, official December 2017.
• USP Monograph, Naphazoline Hydrochloride Ophthalmic Solution, USP40-NF35, The United States Pharmacopeia Convention, official December 2017.
• USP Monograph, Naphazoline Hydrochloride and Pheniramine Maleate Ophthalmic Solution, USP40-NF35, The United States Pharmacopeia Convention.