JP- and EP-Compliant Analysis of Impurities of COVID-19 Drug Dexamethasone

Significance of the topic

Dexamethasone is an essential corticosteroid with proven efficacy in reducing mortality among severe COVID-19 patients. Accurate impurity profiling according to pharmacopoeial standards ensures drug safety, efficacy and regulatory compliance when distributing across different countries.

Objectives and Study Overview

This work presents a comparative evaluation of dexamethasone impurity analyses following Japanese Pharmacopoeia (JP) and European Pharmacopoeia (EP) requirements. Key goals include:

• Establishing HPLC conditions for JP and EP impurity assays
• Verifying system suitability parameters
• Assessing method robustness and compliance for global shipment

Methodology and Instrumentation

The study employed high-performance liquid chromatography under two distinct pharmacopoeial protocols:
JP method:

• Column: Shim-pack VP-phenyl (250×4.6 mm, 5 µm)
• Mobile phase: 1.32 g/L ammonium formate buffer (pH 3.6) and acetonitrile (67:33)
• Flow rate: 1.15 mL/min, isocratic
• Column temperature: 25 °C
• Detection: UV at 254 nm

EP method:

• Column: Shim-pack Scepter C18 (150×4.6 mm, 5 µm)
• Mobile phase: gradient from 0 % to 100 % acetonitrile over 40 min (25 % initial)
• Flow rate: 1.2 mL/min
• Column temperature: 45 °C
• Detection: UV at 254 nm

Used Instrumentation

• HPLC system: Shimadzu Nexera lite
• Analytical columns: Shim-pack VP-phenyl and Shim-pack Scepter C18
• Detector: UV-Vis at 254 nm
• Autosampler vials: 1.5 mL amber glass with septa
• Data processing: Shimadzu LabSolutions workstation

Main Results and Discussion

Both JP and EP protocols yielded sharp, well-resolved dexamethasone peaks and related impurities. Retention times were approximately 13 min under JP conditions and varied under the EP gradient. System suitability tests demonstrated:

• Theoretical plates > 14 000 (JP)
• Symmetry factor ≤ 1.0 (JP)
• Peak-to-valley ratio > 4.0 (EP)
• %RSD of peak area < 0.05 % (JP)

The results met or exceeded all pharmacopoeial criteria, confirming method robustness and reproducibility for both monographs.

Benefits and Practical Applications

The validated methods provide:

• Regulatory compliance for domestic and international distribution
• Reliable impurity quantification to ensure patient safety
• Standardized procedures for quality control laboratories

Future Trends and Applications

Advances may include coupling with mass spectrometry for enhanced sensitivity, implementation of ultra-high-pressure liquid chromatography to shorten run times, and integration of automated data analytics to streamline compliance checks across multiple jurisdictions.

Conclusion

A Shimadzu Nexera lite HPLC platform effectively supports both JP- and EP-compliant impurity analyses of dexamethasone. Despite differing stationary phases and elution profiles, each method consistently met system suitability criteria. These workflows facilitate global quality assurance for this critical COVID-19 therapeutic.

Reference

1. Ministry of Health, Labour and Welfare Novel Coronavirus Response Headquarters, Clinical Management of Patients with COVID-19 – A guide for front-line healthcare workers Ver. 2.2, July 17, 2020
2. Japanese Pharmacopoeia 17th Edition, Dexamethasone monograph
3. European Pharmacopoeia 8.8, 01/2014: 0388, Dexamethasone monograph