Improve Your European Pharmacopoeia (Ph. Eur.) and United States (USP) Monographs

Importance of the Topic

High‐throughput laboratories performing quality control on generic pharmaceuticals must follow official monographs from the European Pharmacopoeia (Ph. Eur.) and the United States Pharmacopeia (USP). Reducing analysis time while ensuring resolution and compliance with allowable method adjustments can improve productivity and maintain regulatory standards.

Objectives and Overview of the Article

This guide evaluates standard Ph. Eur. and USP monographic methods for a range of active pharmaceutical ingredients (APIs) and demonstrates how modern core–shell and fully porous HPLC columns can:

• Shorten run times
• Enhance chromatographic resolution
• Stay within eluotropic and system‐suitability criteria

Methodology and Instrumentation

Monographs covered include allopurinol, amlodipine besylate, atenolol, carvedilol, clarithromycin, fluconazole, fluoxetine HCl, metoprolol tartrate, oxycodone HCl, paroxetine HCl, potassium clavulanate, pravastatin sodium, simvastatin, tamsulosin HCl, tramadol HCl, and trimethoprim plus USP standards for ibuprofen, lovastatin, fluticasone propionate, metformin HCl, and others. Comparative experiments replaced standard 5 µm fully porous columns with:

• Core–shell C18 (Kinetex®) and core–shell C8
• Fully porous C18(2) (Luna®), biphenyl, phenyl-hexyl, HILIC and cation/anion exchange phases

Detection was by UV spectrophotometry (205–295 nm) under isocratic or gradient elution. System suitability tests followed Ph. Eur. Chapter 2.2.46 and USP <621> guidelines.

Main Results and Discussion

Core–shell columns consistently reduced elution times by 30–70% while maintaining or improving resolution (Rs often >2.0 vs. baseline). Examples include:

• Allopurinol related substances: run time cut from ~10 min to ~8 min; Rs B/C improved from 1.4 to >1.7
• Amlodipine besylate: analysis time reduced from ~20 min to ~5 min; Rs B/G increased to >13
• Atenolol: run time shortened from ~33 min to ~12 min; Rs I/J rose to >3.7

Benefits and Practical Applications

By adopting core–shell technology, QC laboratories can:

• Increase sample throughput without method revalidation
• Reduce solvent consumption and waste
• Meet or exceed monograph system‐suitability requirements
• Maintain flexibility by applying allowable pH, flow or column dimension adjustments per Ph. Eur. and USP

Future Trends and Applications

The adoption of sub-3 µm and core–shell phases continues to grow, driven by:

• Ultra-high‐performance LC (UHPLC) instruments
• Green analytical chemistry goals
• Automated method scouting with diverse stationary phases
• Integration with mass spectrometry for peak identification

Conclusion

Upgrading official monograph methods with advanced column technologies allows pharmaceutical laboratories to enhance resolution, accelerate analyses, and remain fully compliant with Ph. Eur. and USP requirements, ultimately optimizing QC workflows.

References

European Pharmacopoeia Monographs 0060, 0576, 0703, 1028, 1104, 1140, 1491, 1563, 1651, 1681, 1745, 1793, 2059, 2131, 2283, 2287 USP Chapters <621>, Monographs for Amlodipine Besylate, Clavulanate Potassium, Fluticasone Propionate, Ibuprofen, Lovastatin, Metformin Hydrochloride, Pravastatin Sodium, Trimethoprim