Accelerating method development with Thermo Scientific Vanquish HPLC and UHPLC Method Development Systems

Importance of the Topic

The development of robust liquid chromatography methods is essential to ensure product quality and regulatory compliance across pharmaceutical, industrial and research laboratories. Method scouting and optimization typically require extensive manual effort and expert knowledge to balance separation parameters such as mobile phase composition, column chemistry and temperature. Automating these tasks accelerates method development, reduces analyst time and improves reproducibility under the Quality by Design framework.

Objectives and Overview of the Study

This article highlights the integration of Thermo Scientific Vanquish HPLC and UHPLC hardware with ChromSwordAuto Chromeleon Connect software for automated method development and validation. The goal was to streamline column and solvent scouting, gradient optimization, robustness testing and compliance with ICH guidelines, while minimizing manual intervention and analyst expertise.

Methodology and Instrumentation

The automated method development system comprises:

• Vanquish HPLC and UHPLC platforms: Core HPLC, Flex and Horizon UHPLC modules
• Method Scouting Kits: Viper fluidic kit for up to four column chemistries and solvent extension valve for up to ten mobile phases
• Column compartments: up to six temperature controlled zones with Accucore column selectivity kit offering multiple chemistries
• Detection: Diode array detection for UV absorbance, charged aerosol detection for universal response and single quadrupole mass spectrometry for peak confirmation
• Software: ChromSwordAuto Scout, Developer and AutoRobust modules integrated with Chromeleon CDS and Data Vault storage
• eWorkflow library: Predefined method templates from AppsLab and ICH validation templates in Chromeleon Extension Pack

Main Results and Discussion

Automated column and solvent scouting produced a preliminary method within three to five scouting runs. Gradient optimization refined separation of green tea catechins, resolving eleven target peaks including epigallocatechin and caffeine, which initially coeluted. The complete development required 50.5 hours of instrument time and 24 hours of analyst time. AutoRobust evaluated method robustness via multivariate designs, defining a design space for method parameters. ICH Q2 R1 validation workflows in Chromeleon generated accuracy, precision and linearity reports automatically, demonstrating full compliance through the method life cycle.

Benefits and Practical Applications

• Reduced development time from weeks to days and from months for complex separations
• Minimal operator expertise required, enabling nonexperts to deploy robust methods
• Unattended operation supports continuous 24/7 method development
• Comprehensive compliance through integrated validation and data management
• Flexible application across diverse sample types and regulatory requirements

Future Trends and Potential Applications

Advances in artificial intelligence and machine learning will further enhance automated decision making for complex separations. Integration of cloud based data analytics and remote monitoring may expand collaborative method development across sites. Expanded detector portfolios and microfluidic front ends promise to extend automation to novel separation techniques beyond reverse phase liquid chromatography.

Conclusion

The Thermo Scientific Vanquish method development ecosystem combines advanced hardware, universal detection and smart software to accelerate and simplify HPLC and UHPLC method development. By reducing manual intervention and ensuring compliance, it empowers laboratories to achieve high quality results with minimal resources and expertise.

References

1. Thermo Fisher Scientific Appslab Library of Analytical Applications
2. Grosse S, Park SH, De Pra M, Steiner F. Automated method development in HPLC for the quantitative determination of catechins in tea. Thermo Fisher Scientific Application Note 72830, 2018.
3. Grosse S, Quinn S, De Pra M, Steiner F. Method validation based on ICH guidelines of a USP assay method of acetaminophen. Thermo Fisher Scientific Application Note 73374, 2020.