Extractables, Leachables, and Food Contact Materials

Significance of Extractables and Leachables

Extractables and leachables analysis is critical for ensuring the safety and quality of pharmaceuticals, cosmetics, food contact materials, and related consumer products. Extractables—compounds released under exaggerated conditions—and leachables—compounds migrating during normal use—can pose health and regulatory risks if not identified and controlled. Regulatory frameworks in the US, EU, and other regions mandate thorough characterization of container closure systems and packaging materials to prevent harmful contamination, protect brands, and avoid product recalls.

Objectives and Study Overviews

The application notes encompass a wide range of studies using different matrices (pharmaceutical formulations, e-cigarettes, kitchenware, food packaging, and recycled paper). Key goals include: identifying plastic additives, polymer degradants, and non-intentionally added substances (NIAS); confirming known impurities; screening for unexpected migrants; and quantifying regulated analytes such as primary aromatic amines (PAAs). Each study sought to demonstrate advanced analytical approaches to streamline extractables and leachables testing workflows.

Analytical Methodologies and Instrumentation

Advanced separation and detection techniques were showcased:

• UHPLC and HPLC–UPLC hybrid systems (ACQUITY Arc, I-Class) coupled with PDA and single-quadrupole (QDa) or triple quadrupole (Xevo TQ-S) detection for targeted and impurity profiling.
• Supercritical fluid chromatography (UPC2) and supercritical fluid extraction (MV-10 ASFE) for rapid, solvent-saving sample preparation and analysis of polar and non-polar extractables.
• Gas chromatography coupled to time-of-flight mass spectrometry (APGC–QTof) and direct atmospheric pressure solids analysis (ASAP) probes for volatile/semi-volatile screening.
• High-resolution mass spectrometry with data-independent acquisition (MSE and HDMSE) on Xevo G2-XS QTof and SYNAPT G2 systems, generating accurate mass precursor and fragment ions in a single injection.

Informatics Workflows

UNIFI Scientific Information System and MarkerLynx™ XS Application Manager provided integrated workflows for non-targeted screening and elucidation:

• Building custom scientific libraries of known extractables and leachables.
• Targeted screening against accurate-mass databases for quantitation and compliance checks.
• Sample comparison (binary and multivariate analysis) to pinpoint unique or elevated markers across sample groups.
• Discovery tools for automatic elemental composition calculation, ChemSpider database searches, and fragment-matching.
• MassFragment™ Software for automated structural assignment of fragment ions, enabling high-confidence identification without authentic standards.

Main Findings and Discussion

Key outcomes across investigations included:

• Identification and quantitation of polymer additives (e.g., Irganox antioxidants, phthalate plasticizers, UV stabilizers) and NIAS (e.g., BHT, oleamide, erucamide) in pharmaceutical packaging and e-cigarette components.
• Rapid, high-throughput screening of primary aromatic amines in polyamide kitchenware below regulatory limits (0.78–100 ng/mL), using pH-adjusted samples and post-column formic acid addition to enhance sensitivity on Xevo TQ-S micro.
• Detection of benzoguanamine migrants in infant formula packaging using UPLC/QTof and MS E, followed by fragment confirmation via MS/MS.
• Direct solids analysis of nylon utensils with an ASAP probe and ToF-MS for PAA screening in under 3 minutes per sample, and retrospective detection of phthalates (DBP, DEHP) in the same datasets.
• Uncovering UV-ink components (e.g., 2-ethylhexyl-4-dimethylaminobenzoate) and mineral-oil migrants from recycled paper and board food packaging using UPLC/ToF-MS and MassFragment elucidation.

Benefits and Practical Applications

These advanced analytical and informatics approaches enable:

• Streamlined sample preparation with reduced solvent use and analysis time via SFE and direct probe methods.
• Comprehensive chemical profiling in a single run, capturing both targeted and unknown contaminants.
• Reduced false positives and increased confidence through accurate mass, isotope pattern matching, and fragment assignment.
• Rapid method conversion between HPLC, UHPLC, UPC2, and GC to meet diverse regulatory assays.

Future Trends and Opportunities

Emerging trends include integration of ion mobility separation (HDMSE), further miniaturization and automation of extraction workflows, and adoption of AI-driven spectral interpretation. Expansion of spectral and structural databases will enhance identification of NIAS. Real-time in-line monitoring and high-throughput ambient ionization methods promise rapid screening for quality control and regulatory compliance across pharmaceutical, food, and packaging industries.

Conclusion

The collective studies highlight the power of combining state-of-the-art separations (UPLC, UPC2, GC, SFE), high-resolution MS (QTof, TQ-S), and advanced informatics (UNIFI, MarkerLynx, MassFragment) to achieve rapid, reliable, and high-confidence detection, identification, and quantitation of extractables, leachables, and migrants in diverse packaging and consumer products. These integrated workflows pave the way for robust quality assurance, regulatory compliance, and improved consumer safety.