Pharma workflow solutions

Significance of the Topic

Pharmaceutical impurity analysis is critical for ensuring the safety, efficacy, and regulatory compliance of drug products. Sensitive detection of trace-level impurities—such as nitrosamines, residual solvents, and degradation products—supports quality control and risk assessment across drug discovery, development, and manufacturing stages.

Objectives and Overview

This brochure presents a collection of integrated workflow solutions for key analytical challenges in pharmaceutical laboratories. The main goals are:

• Quantitative detection of nitrosamine impurities in ranitidine and similar drug products.
• High-throughput analysis of common active pharmaceutical ingredients (e.g., ibuprofen, cephalosporin antibiotics).
• Assessment of residual solvents according to USP guidelines.
• Method modernization strategies to reduce run times and solvent consumption.

Methodology and Used Instrumentation

Each workflow combines optimized sample preparation, chromatographic separation, and detection:

• Nitrosamine analysis: protein precipitation plates, Acclaim PA2 UHPLC columns, Vanquish Horizon UHPLC system, Orbitrap Exploris 120 mass spectrometer.
• Ibuprofen and API assays: Accucore C18 and Hypersil GOLD HPLC columns, Vanquish Core HPLC system with UV detection.
• Residual solvent testing: headspace autosampler (Thermo Scientific TriPlus), TRACE 1600 GC, TraceGOLD TG-624 and TG-WaxMS columns, GuardGOLD capillary guard columns, Super Clean gas filters.
• Modernization: column ID and particle-size scaling equations to migrate USP monographs from 5 µm to sub-3 µm columns, enabling UHPLC operation and shorter gradients.

Main Results and Discussion

The application data demonstrate:

• Nitrosamines: baseline separation of nine genotoxic impurities at 0.5 ng/mL, meeting FDA guidelines with sub-ppm mass accuracy.
• Ibuprofen: sharp peak shapes and reproducible retention on Accucore C18 columns, aligning with USP specifications for API purity.
• Cephalosporins: improved sensitivity and peak symmetry on Hypersil GOLD columns, enhancing impurity quantitation at low levels.
• Residual solvents: complete resolution of USP Class 2A solvents with Rs > 1.0 on TraceGOLD columns and robust headspace sampling.
• Method modernization: example conversion of pramipexole impurity assay from 5 µm, 4.6 × 150 mm to 1.9 µm, 2.1 × 50 mm UHPLC format, achieving an 80 % reduction in run time and solvent usage.

Benefits and Practical Applications

These integrated workflows offer:

• Regulatory compliance: validated methods that meet USP, FDA, and ICH limits for impurities and solvents.
• Resource efficiency: reduced analysis times and solvent consumption through column miniaturization and UHPLC technology.
• Enhanced sensitivity and selectivity via advanced stationary phases and high-resolution mass spectrometry.
• Modular consumables: user-friendly guard cartridges, low-dead-volume connectors, and performance-certified vials and caps for consistent sample handling.

Future Trends and Potential Applications

Emerging directions include:

• Greater adoption of ultra-high-throughput LC and GC systems to support large-scale biopharmaceutical screening.
• Integration of automated sample preparation—solid-phase extraction plates and magnetic bead workflows—to reduce manual intervention.
• Advances in data analytics and AI-driven peak deconvolution for complex mixture profiling.
• Expanded use of multidimensional chromatography and ion mobility to resolve challenging impurity profiles.

Conclusion

Thermo Fisher Scientific’s end-to-end solutions—from sample prep to separation and detection—enable pharmaceutical laboratories to achieve confident impurity analysis, streamline workflows, and maintain regulatory compliance. Implementing modernized methods and high-performance consumables drives operational efficiency and analytical quality across discovery, development, and QC environments.

References

• Application note: HRAM LC-MS method for determination of nitrosamine impurities in drugs. Thermo Fisher Scientific.
• AppsLab library: Improved analysis of ibuprofen and valerophenone using Accucore C18 column. Thermo Fisher Scientific.
• Application note: Routine-grade performance of static headspace autosampler for residual solvent analysis (USP <467>). Thermo Fisher Scientific.