15th Multidimensional Chromatography Workshop Abstract book

Importance of Multidimensional Chromatography in Analytical Chemistry

Multidimensional separation techniques such as comprehensive two-dimensional gas chromatography (GC×GC) and two-dimensional liquid chromatography (2D-LC) are increasingly vital for resolving complex mixtures across industries. Their enhanced peak capacity and selectivity provide in-depth characterization of compounds in pharmaceuticals, environmental monitoring, food and flavor analysis, forensics, and petrochemicals.

Study Objectives and Overview

This body of work presents advances in method development, instrumentation, data processing, and applications of GC×GC and 2D-LC. Key aims include:

• Evaluating benefits and limitations of GC×GC in government and industrial labs
• Developing performance reference standards for system validation
• Integrating GC×GC with TOFMS and FID for quantitative group-type analysis
• Extending multidimensional chromatography to pharmaceutical impurity profiling, antibody PTM monitoring, and small-molecule separation
• Streamlining method development via automated column screening and web-based simulators
• Applying TD-GC×GC-TOFMS to non-targeted biomarker discovery in breath, house dust, river water, and body odor

Methodology and Instrumentation

Techniques and hardware innovations include:

• Flow- and thermal-modulated GC×GC coupled to TOFMS, FID, and soft-ionization sources (FI, FD)
• On-line 2D-LC and LC×SFC systems with multi-column valves, trapping modes, and make-up flows
• Passive sampling devices (SPMD, silicone rubber) for environmental VOC collection
• Headspace-SPME and thermal desorption tubes for breath, body fluid, and aroma analysis
• Advanced data processing: tile-based Fisher-ratio, PCA/PLS, chemometric workflows, and open-source Python tools

Main Results and Discussion

Highlights across studies:

• GC×GC reveals UCM regions, trace-level additives, and cross-contaminants undetected by 1D methods
• 2D-LC (RPLC×RPLC, RPLC×HILIC, SEC×RPLC) accelerates impurity profiling and peak-purity assessment in drug development
• On-line multidimensional LC/MS automates method screening across chiral/achiral columns
• Non-targeted GC×GC-TOFMS discriminates disease biomarkers in breath and biological matrices with high accuracy
• Passive sampling plus GC×GC–TOFMS provides holistic water quality assessment, identifying pesticides, pharmaceuticals, and pollutants
• Machine learning and chemometrics enable automated alignment, hitlist generation, and longitudinal biomarker validation

Benefits and Practical Applications

Multidimensional chromatography offers:

• Enhanced separation of isomers and co-eluting analytes
• Improved sensitivity for trace compounds via modulation compression
• Robust non-target screening for biomarker discovery and quality control
• Streamlined workflows through automated column selection and software-assisted data mining

Future Trends and Potential Uses

Emerging directions include:

• Integration of ambient ionization sources (e.g., DBD) with GC×GC for high-flow MS detection
• Further democratization of data processing via open-source, cloud-based platforms
• Expansion of LC×LC and LC×SFC for novel biotherapeutic and polymer analyses
• Advanced chemometric models to address multi-factor variance and real-time process monitoring

Conclusion

Collectively, these studies demonstrate that multidimensional chromatography, coupled with high-resolution detection and modern data analytics, is transforming analytical capabilities. Continued instrument innovation and software democratization will be key to broader adoption in routine and regulatory environments.

Reference

[1] Weggler BA, et al. J. Chromatogr. A 1635 (2021): 461721.