Combined LC/MS and GC/MS Approach for Analysis of Extractables and Leachables in Complex Matrices Using High Resolution Mass Spectrometry

Importance of the Topic

The migration of extractable and leachable compounds from polymeric materials into pharmaceutical or medical device environments can impact product safety, performance and regulatory compliance. A comprehensive analytical strategy combining high-resolution gas chromatography–mass spectrometry (GC/Q-TOF) and liquid chromatography–mass spectrometry (LC/Q-TOF) is essential to detect volatile, semi-volatile and non-volatile species across a wide chemical space.

Objectives and Study Overview

This work aimed to establish an integrated, non-targeted workflow for extractables and leachables (E&L) analysis in complex matrices. Rubber syringe gaskets were extracted in tetrahydrofuran for six months, and catheters from four brands were extracted in 50% ethanol/water at 37 °C for three weeks. Both extract types were analyzed by high-resolution GC/Q-TOF and LC/Q-TOF to maximize compound coverage, and statistical tools were applied to compare profiles between materials.

Methodology and Instrumentation

Extractions:

• Rubber gaskets: Room-temperature THF extraction for six months.
• Catheters: 1:1 EtOH/H2O at 37 °C for three weeks.

Analysis conditions:

• GC/Q-TOF on a DB-5Q column, splitless injection, oven to 325 °C, mass range m/z 50–1000.
• LC/Q-TOF with C18 reversed-phase column, gradient from water to methanol (0.05% formic acid, 2.5 mM ammonium formate), ESI positive mode, m/z 40–1700, auto MS/MS.

Data processing was performed in MassHunter for deconvolution, library matching (NIST, Agilent PCDL) and exact mass confirmation; Mass Profiler Professional (MPP) facilitated statistical comparisons.

Main Results and Discussion

The dual-platform approach identified hydrocarbons, oxygenates, phthalates, antioxidants, plasticizers, amides and other classes. GC/Q-TOF uniquely detected nonpolar and aromatic hydrocarbons (e.g., alkylbenzenes, long-chain alkanes), while LC/Q-TOF provided complementary detection of polar, high-mass species (e.g., esters, amides, polymer additives). Principal component analysis of catheter extracts revealed distinct clustering by material type, and Venn diagrams illustrated both shared and unique E&L profiles. The ExactMass tool increased confidence in compound assignments by matching fragment ions to predicted molecular formulas.

Benefits and Practical Applications

Integrating high-resolution GC/MS and LC/MS ensures broad chemical coverage for non-targeted E&L studies, supporting risk assessment, regulatory submissions and quality control of medical device materials. Centralized informatics workflows improve data integrity, streamline compound identification and accelerate decision making.

Future Trends and Potential Applications

Advances in ultra-high-temperature, low-bleed GC columns will extend volatility ranges. Incorporation of ion mobility separation will enhance isomer resolution. Machine learning–driven spectral deconvolution and predictive modeling may automate non-targeted screening, reduce false positives and deepen understanding of material–extractive interactions.

Conclusion

A robust combined high-resolution GC/Q-TOF and LC/Q-TOF workflow was developed for non-targeted profiling of extractables and leachables in polymeric matrices. The method delivers comprehensive coverage, reliable compound identification and differentiated profiles across materials, strengthening safety evaluation and quality assurance for pharmaceutical and medical device applications.