Pharma Materials Study: GC-MS Identification of Extractables and Leachables from Elastomer Material

Importance of the Topic

The compatibility of pharmaceutical packaging materials with drug products is critical to ensure safety and efficacy. Elastomeric components can release volatile and semi volatile compounds that may migrate into formulations and impact product performance or patient health. Comprehensive extractables and leachables studies support material selection and regulatory compliance.

Objectives and Study Overview

This application study aims to identify extractable compounds from an elastomeric plunger intended for dental injectable cartridges. Using gas chromatography mass spectrometry with parallel flame ionization detection, the work evaluates headspace volatiles and liquid extracts obtained under diverse conditions. Deconvolution software and library matching are applied for compound identification and structural elucidation of unknown peaks.

Methodology and Instrumentation

Sample preparation involved:

• Headspace sampling of intact plungers for volatile analysis
• Aqueous extraction followed by dichloromethane partition
• Direct dichloromethane extraction with BSTFA derivatization
• Isopropanol extraction of semi volatile species

Used instrumentation:

• Thermo Scientific TRACE 1310 GC with split splitless inlet
• Parallel FID and ISQ single quadrupole mass spectrometer
• TriPlus RSH autosampler for liquid and headspace injections
• TraceGOLD 5MS capillary column and helium carrier gas

Data acquisition included full scan MS at 25 to 700 dalton and deconvolution using AMDIS software. Unknown spectra were further interpreted with Mass Frontier.

Main Results and Discussion

Headspace analysis revealed a series of low molecular weight hydrocarbons and carbonyls with library matches above 75 percent. Liquid dichloromethane extracts contained aromatic solvents and phthalate esters, while derivatized extracts displayed fatty acids and siloxanes. The isopropanol extract highlighted long chain nitriles, esters and polymer residues. Retention times aligned perfectly between MS and FID channels. AMDIS deconvolution enabled clear mass spectra extraction even in coeluting regions. Mass Frontier proposed plausible structures for unidentified peaks at specific retention times, enhancing confidence in assignments.

Benefits and Practical Applications

This combined GC FID MS workflow offers:

• Comprehensive profiling of volatile and semi volatile extractables
• High confidence identification through deconvolution and library search
• Parallel FID detection supporting future quantitation
• Efficient unknown elucidation using fragmentation software
• Applicable to routine quality control and material compatibility assessments

Future Trends and Opportunities

Emerging techniques in high resolution and multidimensional GC MS, expanded spectral libraries and automated data processing will further improve extractables characterization. Standardization of workflows and regulatory harmonization will enhance safety evaluations of pharmaceutical packaging.

Conclusion

An integrated GC FID MS approach with targeted extraction strategies provides a robust solution for extractables identification from elastomeric materials. Deconvolution and structural interpretation complement library searches to achieve reliable compound profiling for product safety and quality assurance.

References

1 FDA Guidance for Industry Container Closure Systems for Packaging Human Drugs and Biologics 1999
2 CPMP QWP 4359 03 Guideline on Plastic Immediate Materials 2005
3 Sehnal N et al Compatibility of Parenterals and Contact Materials STP Pharma Pratiques 2013
4 Norwood DL et al Best Practices for Extractables and Leachables Pharm Res 2008
5 Jenke D Compatibility of Pharmaceutical Products and Contact Materials Wiley 2009
6 United States Pharmacopeia Chapters 1663 and 1664 Pharmacopeial Forum 2013
7 Mallard WG Reed J AMDIS User Guide NIST 1997
8 Soloman S et al Climate Change 2007 IPCC Technical Summary
9 Mass Frontier Manual HighChem 2014
10 Thermo Fisher Scientific Application Note 10398 2014