Modernization of the USP Monograph for the Analysis of Miconazole Nitrate Cream using CORTECS Phenyl 2.7 μm Columns

Significance of the Topic

Modern pharmaceutical analysis demands efficient and robust quality control methods. The monograph for miconazole nitrate cream in USP plays a vital role in ensuring antimicrobial efficacy and patient safety. Modernizing legacy HPLC protocols with advanced column technologies can streamline workflows and reduce costs without compromising regulatory compliance.

Objectives and Study Overview

This work aimed to adapt the existing USP monograph method for miconazole nitrate cream by replacing a conventional 5 µm, 250 mm phenyl column with a high-efficiency CORTECS Phenyl 2.7 µm, 100 mm column. The goal was to demonstrate equivalent separation performance, improved sensitivity, and faster analysis times under USP <621> guidelines.

Methodology and Instrumentation

The study compared two chromatographic setups:

• XBridge Phenyl, 5 µm, 4.6 x 250 mm column on an HPLC system (Alliance e2695 with 2489 UV/Vis detector)
• CORTECS Phenyl, 2.7 µm, 3.0 x 100 mm column on an UPLC system (ACQUITY UPLC with PDA detector)

Both methods used an isocratic mobile phase of methanol/acetonitrile/tetrahydrofuran/1% triethylamine (25/20/15/40, v/v, pH 2.5) at 225 nm detection. Sample preparation involved dispersing the miconazole cream in mobile phase, ultrasonic extraction, filtration, and injection volumes of 10 µL (HPLC) and 1.7 µL (UPLC).

Main Results and Discussion

• Resolution between miconazole and benzoic acid exceeded USP requirements, with values of 17.4 (HPLC) and 15.5 (UPLC).
• Theoretical plate counts for miconazole were above 14 000 for both columns, meeting the minimum criterion of 7 500.
• Peak sensitivity increased by 35% on the CORTECS column, enabling more reliable quantification.
• Overall run time was reduced by approximately threefold, delivering faster throughput without revalidation outside USP <621> limits.
• Labeled content of miconazole nitrate was within the 90.0–110.0% range (96.3% HPLC, 94.9% UPLC).

Benefits and Practical Applications

• Significant time savings in routine QC analysis.
• Enhanced sensitivity supports trace detection and impurity profiling.
• Reduced solvent consumption and solvent waste generation.
• Simplified adherence to USP <621> modernization guidelines.
• Easy integration into existing laboratory workflows.

Future Trends and Possibilities

Advancements in column technology and UPLC systems are poised to further accelerate pharmaceutical testing. Digital integration, automation of sample preparation, and the use of high-throughput multiplexed platforms will enhance lab efficiency. Continued development of solid-core particle columns with novel chemistries may expand applications to more complex matrices and multi-analyte assays.

Conclusion

The replacement of a traditional phenyl HPLC column with a high-efficiency CORTECS Phenyl 2.7 µm column under USP <621> guidelines successfully modernized the miconazole nitrate cream monograph. Analytical performance matched or exceeded USP criteria while delivering faster run times and improved sensitivity, demonstrating a practical pathway for upgrading legacy methods in pharmaceutical quality control.

Reference

• Bonnie A. Alden and Jacob N. Fairchild. Modernization of the USP Monograph for the Analysis of Miconazole Nitrate Cream using CORTECS Phenyl 2.7 µm Columns. Waters Corporation, March 2016.