Identification and Quantitation of Plastic Additives in Medicine Containers by HR LC-MS, GC-MS and ICP-MS

Importance of the Topic

Plastic additives present in medical and pharmaceutical containers can migrate into drug products, potentially posing health risks and failing regulatory standards. Comprehensive profiling of these extractables and leachables is essential for ensuring patient safety and maintaining product integrity.

Objectives and Study Overview

This study aimed to identify and quantify a range of plastic additives in commercial polypropylene pill bottles. High-resolution LC-MS, GC-MS and ICP-MS techniques were combined with advanced data-processing tools to achieve confident detection, structural elucidation and accurate quantitation.

Methodology

Sample Preparation:

• Filled bottles with isopropanol (IPA) for organic extractables and with 2 % nitric acid for metal analysis.
• Incubated IPA extracts at 50 °C for five days; acid extracts at room temperature for 24 hours.
• Injected extracts directly into LC-MS, GC-MS and ICP-MS systems.

Data Processing:

• Employed SIEVE 2.1 for non-targeted peak extraction and component alignment.
• Used Mass Frontier 7.0 and the mzCloud spectral database for fragment annotation and structure confirmation.

Used Instrumentation

• Thermo Scientific Q Exactive Orbitrap mass spectrometer with Dionex Ultimate 3000 RS UHPLC.
• Thermo Scientific ISQ single-quadrupole GC-MS with Trace Ultra GC and Triplus RSH autosampler.
• Thermo Scientific iCAP Q ICP-MS operated in helium KED mode for elemental screening.

Main Results and Discussion

HR-LC-MS and GC-MS analyses identified multiple antioxidants, plasticizers and phenolic stabilizers in the IPA extracts. Accurate-mass data and MS/MS spectra enabled confident structure assignments. Calibration curves for selected antioxidants showed linear responses across 1–1000 ppm. ICP-MS results demonstrated that all USP <232>-regulated metals and additional trace elements were detected below threshold limits, confirming material compliance.

Benefits and Practical Applications

This integrated workflow allows rapid, comprehensive screening of extractable and leachable compounds in pharmaceutical packaging. It supports regulatory compliance testing, risk assessment and quality control of container materials.

Future Trends and Opportunities

Advances in high-resolution mass spectrometry, expanded spectral libraries and AI-driven spectral interpretation will enhance non-targeted screening of unknown compounds. Automated workflows and closer alignment with evolving regulatory guidelines will broaden applications to food, beverage and medical device packaging assessment.

Conclusion

The complementary use of HR-LC-MS, GC-MS and ICP-MS, combined with robust software tools, provides a streamlined, reliable approach to identify, quantify and confirm plastic additives and trace metals in medical containers, ensuring consumer safety and regulatory compliance.