Analytical Solutions for Extractables, Leachables, and Migration Testing

Importance of the Topic

Packaging and product-contact materials play a critical role in protecting pharmaceuticals, food, and cosmetics from external contamination. However, these materials can themselves release chemical constituents—known as extractables and leachables—into the final product. Uncontrolled migration of these compounds poses risks to human health and brand integrity, while tightening regulations demand more rigorous analytical testing. Effective monitoring of extractables and leachables is therefore essential to guarantee product safety and regulatory compliance.

Aims and Overview of the Article

This article reviews advanced analytical strategies to identify, characterize, and quantify extractable and leachable compounds in contact materials. It highlights the challenges faced in migration testing, including chemical diversity, matrix complexity, and evolving regulatory requirements. The objectives are to illustrate a comprehensive workflow—from controlled extraction studies to routine quality control—and to present instrument platforms and software solutions that boost efficiency, sensitivity, and data integrity.

Methodology and Instrumentation

Analytical approaches combine liquid chromatography (LC), gas chromatography (GC), supercritical fluid extraction (SFE), and mass spectrometry (MS) with data processing tools. Key instrumentation includes:

• ACQUITY UPLC I-CLASS coupled to XEVO G2-XS QTof MS for high-resolution separations and accurate mass measurements.
• Atmospheric pressure GC (APGC) interfaces providing soft ionization and improved selectivity over conventional EI sources.
• MV-10 ASFE supercritical fluid extraction system for rapid, eco-friendly sample preparation across a broad polarity range.
• ACQUITY UPC2 convergence chromatography with Trefoil, Torus, and Viridis SFC columns for faster chiral and achiral separations using CO₂ mobile phase.
• VION IMS-QTof for ion mobility separation, enabling collision cross section (CCS) measurements to enhance compound confirmation.
• UNIFI Scientific Information System for integrated data acquisition, processing, multivariate analysis, and compliance reporting.
• ACQUITY ARC dual-path LC platform with Empower CDS and QDa mass detector for high-throughput routine QC and release testing.
• XBridge and CORTECS columns providing robustness and peak capacity across a wide pH range and particle sizes.

Main Results and Discussion

Controlled extraction studies demonstrated reliable detection of unknown polymer additives, degradation products, and contaminants at trace levels. LC-MS/MS workflows using data-independent acquisition (MSE) yielded comprehensive structural data, while APGC-QTof improved molecular ion detection with reduced fragmentation. SFE coupled to SFC accelerated screening across multiple solvents without extensive sample handling. Ion mobility separation added orthogonal selectivity to distinguish co-eluting species. Binary comparison in UNIFI facilitated direct spectral comparison between blank and sample extracts, streamlining unknown identification and reducing bottlenecks.

Benefits and Practical Applications of the Method

These integrated solutions enable laboratories to:

• Maximize analytical throughput and reduce method development time.
• Obtain high-quality structural information for targeted and non-targeted screening.
• Ensure trace-level detection of leachables to meet regulatory thresholds.
• Simplify data management and compliance reporting.
• Minimize solvent usage and analytical costs.
• Accelerate product development cycles and mitigate recall risks.

Future Trends and Opportunities

As single-use systems and recycled packaging grow in importance, demand for robust extractables/leachables testing will intensify. Emerging trends include increased adoption of high-field ion mobility, automation, artificial intelligence for spectral deconvolution, and cloud-based informatics for collaborative data review. Continued advances in column chemistry and source interfaces will further enhance sensitivity and selectivity, while regulatory bodies refine guidelines to address novel materials and biologics.

Conclusion

Comprehensive analytical workflows combining UPLC, GC, SFE, SFC, high-resolution MS, and advanced informatics are crucial for rigorous extractables and leachables testing. These solutions deliver the sensitivity, speed, and data traceability needed to safeguard product safety, ensure compliance, and support efficient product development.

Reference

Waters Corporation. Extractables and Leachables: Analytical Solutions for Extractables, Leachables, and Migration Testing. May 2017.