Applying Analytical Method Greenness Scoring to the USP Monograph of Naproxen; Improving the Sustainability of Validated Methods by Modernizing to Newer Technology

Significance of the topic

The sustainability of analytical workflows is critical to reducing environmental impact and operational costs in quality control laboratories

Many validated methods such as USP monographs remain fixed in their original configurations and cannot be altered without extensive revalidation This creates a barrier to implementing greener practices

Objectives and Overview

This study revisits the modernization of the USP monograph assay for naproxen sodium tablets and applies the Analytical Method Greenness Score AMGS metric across three liquid chromatography platforms to quantify sustainability improvements

Methodology and Instrumentation

The original USP monograph method was replicated on conventional HPLC and then transferred to UHPLC and UPLC systems employing sub two micrometer columns with an isocratic mobile phase of acetonitrile water and acetic acid Key parameters such as flow rate run time injection volume and number of injections for system suitability and sample replicates were maintained across platforms The AMGS values were calculated using the ACS Green Chemistry Institute AMGS calculator

Main Results and Discussion

Equivalent chromatographic performance was achieved on all three systems while modernized configurations yielded substantial reductions in analysis time and solvent consumption A lifetime study of ten thousand injections demonstrated that UPLC methods required seven days and significantly lower solvent cost compared to fifty five days for HPLC Application of the AMGS metric revealed Greenness scores of approximately 110 for the HPLC method 22 for the UHPLC configuration and under 10 for the UPLC system indicating marked sustainability gains driven primarily by reduced instrument energy and solvent use

Benefits and Practical Applications

• Fourfold to thirteenfold reduction in solvent usage
• Eightfold decrease in analytical run time
• Higher throughput with no need for full method revalidation
• Lower operational and waste disposal costs
• Enhanced environmental performance of routine assays

Future Trends and Application Possibilities

Extending modernization to other pharmacopeial and validated methods can further improve laboratory sustainability Advances in column technology core shell phases and integration of real time greenness assessment tools promise to drive greener analytical practices Adoption of digital analytics for remote monitoring and flow chemistry integration offers additional potential to minimize resource use in high throughput environments

Conclusion

Modernizing legacy USP monograph methods to advanced UHPLC and UPLC platforms yields significant environmental and operational benefits Application of the AMGS metric quantitatively confirms that these upgrades reduce solvent waste energy consumption and analysis time without requiring complete revalidation

Instrumentation Used

• Alliance HPLC System
• ACQUITY Arc System
• ACQUITY UPLC H Class PLUS System

References

1. Berthelette KD Walter TH Collins C DeLoffi M Haynes K Reductions in Cost and Time by Modernizing a USP Monograph Method from HPLC to UHPLC and UPLC Instrumentation and Columns Waters Application Note 720007427 November 2021
2. Hicks M Farrell W Aurigemma C Lehmann L Weisel L Nadeau K Lee H Moraff C Wong M Huang Y Ferguson P Introduction of the Analytical Method Greenness Score AMGS Calculator Green Chemistry 21 1816 2019
3. ACS Green Chemistry Institute Pharmaceutical Roundtable AMGS Calculator accessed February 14 2024
4. United States Pharmacopeia USP Monograph for Naproxen Sodium Tablets accessed February 23 2024
5. Calculation of mobile phase solvent cost based on current reagent prices