Application of UPC2 in Extractables Analysis

Significance of the Topic

Extractables from packaging materials pose a potential risk to pharmaceutical and food products, driving stringent regulatory requirements for container closure systems. Traditional workflows often require multiple instruments and extensive sample preparation to accommodate polar and non-polar solvent extracts. UltraPerformance Convergence Chromatography (UPC²) offers a unified platform capable of injecting a broad range of extractable solvents directly, streamlining extractables and leachables studies.

Objectives and Study Overview

The study aimed to demonstrate a single-instrument approach for the analysis of 14 common polymer additives across diverse packaging matrices and extraction chemistries. Key goals included:

• Comparing UPC² performance with conventional GC-MS and UPLC methods
• Evaluating extractables profiles from high-density polyethylene (HDPE), low-density polyethylene (LDPE), ethylene vinyl acetate (EVA) and polyvinyl chloride (PVC)
• Assessing solvent compatibility for hexane, isopropanol (IPA) and water extracts

Methodology

Packaging samples (2 g) were extracted by microwave-assisted digestion in 10 mL of hexane or IPA at 50 °C for 3 h, whereas water extracts were generated by static exposure of 2 g samples to 10 mL water at 50 °C for 72 h.

Chromatographic conditions:

• UPC²: CO₂ with methanol/acetonitrile (1:1) gradient, 2.0 mL/min, 50 °C column temperature, 5–12 min run times
• UPLC: 0.1% formic acid in water/acetonitrile gradient, 0.9 mL/min, 50 °C, 12 min
• GC-MS: HP-5MS column, 35–320 °C temperature program, 40 min

Instrumentation

• ACQUITY UPC² System with PDA detector and SQD mass spectrometer
• ACQUITY UPLC System with UPLC BEH Phenyl column
• GC-MS system equipped with an HP-5MS column
• Empower 3 and MassLynx software for data acquisition and processing

Main Results and Discussion

UPC² delivered equivalent separation of all 14 additives with orthogonal selectivity compared to UPLC and GC. Run time was reduced two-fold versus UPLC and eight-fold versus GC. Water extracts showed no detectable additives, consistent with low water solubility of targeted compounds. LDPE yielded the richest extractable profile among materials. GC-MS suffered from noisy baselines and required targeted ion monitoring, limiting unknown screening. UPC² provided higher peak intensity for IPA and hexane extracts without evaporative reconstitution.

Three antioxidant additives—Irganox 1010, Irganox 1076 and Irgafos 168—were confidently identified in LDPE extracts by retention time matching and MS data, illustrating UPC²’s capability to screen non-volatile and thermally labile substances in a single run.

Benefits and Practical Applications

UPC² enables:

• A unified workflow for polar and non-polar solvent extracts
• Reduced sample preparation and solvent handling
• Faster analysis times, increasing throughput
• Direct injection of diverse extracts for comprehensive screening
• Improved detection of thermally sensitive additives

These advantages translate into streamlined extractables and leachables studies in pharmaceutical, food packaging and industrial supply chain QC environments.

Future Trends and Opportunities

Expanding UPC² applications may include coupling with high-resolution MS for unknown identification, development of targeted quantitative methods for low-level leachables, and integration into automated workflows. Advances in stationary phase chemistries and CO₂ modifiers promise further improvements in selectivity, sensitivity and eco-friendly practices by reducing organic solvent consumption.

Conclusion

ACQUITY UPC² provides a robust, single-platform solution for extractables analysis across a variety of packaging materials and solvent types. It outperforms conventional GC and UPLC in speed, solvent compatibility and analysis of non-volatile or thermally labile additives, offering significant workflow simplification and greater analytical confidence.

References

1. Balogh MP. Testing the Critical Interface: Leachables and Extractables. LCGC. 2011 June.
2. Containers Closure Systems for Packaging Human Drugs and Biologics. FDA Guidance 1999 May.
3. Norwood DL, Fenge Q. Strategies for the analysis of pharmaceutical excipients and their trace level impurities. Am Pharm Rev. 2004;7(5):92, 94, 96–99.