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Importance of the Topic

Advances in pharmaceutical and biopharmaceutical analytics underpin the safe development, robust quality control, and regulatory compliance of modern therapeutics. High-precision chromatography and mass spectrometry workflows are essential to characterize drug candidates, identify metabolites, monitor impurities, and ensure product consistency from discovery through manufacturing.

Objectives and Study Overview

This summary evaluates a comprehensive portfolio of analytical platforms and software solutions designed to streamline workflows across key stages: early discovery and metabolic profiling, extractables and leachables testing, small- and large-molecule bioanalysis, genotoxic impurity and nitrosamine assessment, analytical quality by design, and quality control batch release.

Methodology and Instrumentation

• Chromatography systems: Vanquish Core and Flex UHPLC, Dionex ICS-6000 ion chromatography, Vanquish Core HPLC.
• LC columns: Hypersil GOLD, Accucore Vanquish C18+, Extreva ASE extractables, Acclaim 120 C18.
• Detectors and MS platforms: Orbitrap Exploris 240, Orbitrap Tribrid, Exploris GC, TSQ Altis Plus, TSQ Quantis Plus, ISQ 7610 single quadrupole GC-MS.
• Sample preparation: SOLA SPE plates, Kingfisher automation, SMART Digest kits.
• Software: Xcalibur, Chromeleon CDS, Compound Discoverer with AcquireX, mzCloud database.

Key Results and Discussion

• Metabolite identification was enhanced by combining high-resolution accurate mass (HRAM) data, rapid polarity switching, AcquireX background exclusion, and complementary fragmentation (CID, HCD, UVPD) to increase low-level metabolite detection.
• Extractables and leachables workflows integrated UV, charged aerosol detection, and HRAM MS for comprehensive impurity profiling in plastics and devices, enabling library matching and quantitation without reference standards.
• Bioanalysis of small molecules achieved fast separation and robust quantitation via SPE cleanup, UHPLC columns, and high-resolution SRM on TSQ Altis Plus, while large molecule workflows utilized automated affinity capture, SMART Digest, and Orbitrap detection for surrogate peptide quantitation.
• Genotoxic impurity and nitrosamine analysis combined ion chromatography for nitrite/amine precursors with triple quadrupole and HRAM Orbitrap MS for sensitive screening and regulatory compliance in process development and QC.
• Analytical Quality by Design tools and automated method‐scouting kits on Vanquish platforms facilitated rapid optimization of LC conditions, robustness testing, and lifecycle management under AQbD principles.
• Quality control batch release methods were easily transferred across HPLC/UHPLC systems using adjustable delay volumes, compliant software integration, and multi‐detector support for UV, CAD, and MS detection.

Benefits and Practical Applications

• Accelerated decision-making through high-throughput, sensitive, and selective workflows for drug discovery and development.
• Improved confidence in metabolite annotation, impurity profiling, and batch release to reduce re‐analysis and risk of noncompliance.
• Enhanced method robustness and transferability across laboratories, boosting productivity and regulatory readiness.

Future Trends and Opportunities

• Integration of AI-driven data analysis to further automate compound identification and structural elucidation.
• Expansion of HRAM MS applications for emerging modalities such as oligonucleotide and cell-based therapies.
• Development of greener analytical practices with reduced solvent use and modular sample prep systems.

Conclusion

The combined suite of advanced chromatography, mass spectrometry, sample preparation, and software platforms delivers end-to-end analytical solutions for pharmaceutical and biopharmaceutical workflows. By leveraging high resolution, automation, and AQbD principles, laboratories can achieve superior data quality, faster throughput, and reliable regulatory compliance across the therapeutic lifecycle.

References

• Thermo Fisher Scientific product brochures and application notes on pharmaceutical workflows.
• Thermo Fisher Scientific technical documentation for Orbitrap Exploris, TSQ Altis, Vanquish UHPLC, and Chromeleon CDS.