Simultaneous Analysis of Carboxylic Anhydrides and Hydrolysates Using Supercritical Fluid Chromatography

Importance of the Topic

Supercritical fluid chromatography (SFC) enables the direct analysis of water-sensitive carboxylic anhydrides without hydrolysis. By using supercritical CO2 as the main mobile phase, SFC minimizes the use of harmful organic solvents and avoids water or alcohol in the mobile phase, reducing sample decomposition and environmental impact.

Objectives and Study Overview

The study aimed to develop a robust SFC method for simultaneous separation and quantification of carboxylic anhydrides and their hydrolysis products. Key goals included:

• Screening six Shim-pack UC stationary phases to find the most selective column
• Optimizing chromatographic parameters to achieve baseline separation of four phthalic anhydride isomers
• Creating a single-run procedure for both anhydrides and hydrolysates via on-line modifier switching

Methodology and Instrumentation

A Shimadzu Nexera UC SFC system equipped with a photodiode array detector and an automated modifier-switching valve was employed. Method development was automated using dedicated software for rapid screening of mobile phases and columns, reducing manual workload and error risk.

Použitá instrumentace

• Supercritical Fluid Chromatograph: Shimadzu Nexera UC
• Columns (250 mm × 4.6 mm I.D., 5 µm): UC-Diol II, UC-Sil II, UC-PolyVP, UC-PolyBT, UC-PBr, UC-ODS
• Detection: PDA (300 nm) with high-pressure flow cell
• Modifier Pump and Switching Valve for on-line change between acetonitrile and 0.1% phosphoric acid in methanol

Key Results and Discussion

• Shim-pack UC-PolyBT provided the best baseline separation (resolution >2.1) of four model anhydride isomers in ~7 min.
• Calibration curves from 5–125 mg/L showed excellent linearity (R2 > 0.9993) and repeatability (%RSD area < 1.0, retention time < 0.9).
• Simultaneous analysis after modifier switching successfully separated eight analytes (four anhydrides and four hydrolysates) with high reproducibility.
• Hydrolysate peaks achieved %RSD < 1.1 for peak area and < 0.83 for retention time, with resolution > 1.5.

Benefits and Practical Applications

• Eliminates pre-hydrolysis steps, streamlining sample preparation.
• Reduces organic solvent consumption and environmental footprint by using CO2.
• Accelerates method development through software-driven column and mobile phase screening.
• Facilitates impurity profiling and stability testing in polymer quality control and research.

Future Trends and Opportunities

• Coupling SFC with mass spectrometry for enhanced sensitivity and compound identification.
• Extending SFC approaches to other moisture-labile or labile functional groups.
• Designing new, more sustainable stationary phases and green modifiers.
• Applying artificial intelligence for automated method optimization and predictive performance.

Conclusion

This work highlights the effectiveness of SFC for rapid, reliable analysis of carboxylic anhydrides and their hydrolysates in a single run. Utilizing a UC-PolyBT column and on-line modifier switching yields high resolution, precision, and reduced environmental impact, making it ideal for routine QA/QC and research applications.