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

Significance of the Topic

Plastic additives in pharmaceutical packaging can migrate into medicines and pose health risks. Comprehensive characterization of these extractables and leachables is critical for regulatory compliance and consumer safety.

Objectives and Study Overview

This study aims to identify and quantify plastic additives in polypropylene medicine containers using complementary analytical techniques: high-resolution liquid chromatography–mass spectrometry (HR LC-MS), gas chromatography–mass spectrometry (GC-MS), and inductively coupled plasma mass spectrometry (ICP-MS). Data processing leverages advanced software and spectral databases to ensure confident detection, structural elucidation, and quantification of unknown compounds.

Methodology and Instrumentation

The workflow integrates three analytical platforms:

• Sample Preparation: Commercial polypropylene bottles were filled with isopropanol and extracted at 50 °C for five days; ICP-MS samples were leached with 2 % nitric acid for 24 h.
• HR LC-MS: Separation on a C18 UHPLC column; electrospray ionization in positive mode on an Orbitrap mass spectrometer; full-scan (70 000 resolution) and data-dependent MS/MS (35 000 resolution).
• GC-MS: Split injection into a single quadrupole GC-MS system; detection of volatile and semi-volatile additives.
• ICP-MS: He KED mode on a quadrupole ICP-MS to quantify trace metals according to USP <232> and additional elements.

Main Results and Discussion

HR LC-MS identified over a dozen plastic additives by accurate mass and tandem MS, with molecular formula confirmation via spectral databases and fragmentation software.
GC-MS analysis corroborated LC-MS findings and quantified volatile antioxidants and phthalates over a wide calibration range (1–1000 ppm) with high linearity.
ICP-MS results indicated that all monitored toxic and catalytic metals were below regulatory thresholds, demonstrating container compliance.

Benefits and Practical Applications

The combined analytical strategy enables:

• Comprehensive profiling of extractables and leachables in pharmaceutical packaging.
• Accurate structural identification using high-resolution MS and spectral libraries.
• Quantitative assessment of organic additives and trace metals to meet regulatory standards.

Future Trends and Applications

Ongoing developments in high-resolution instrumentation and spectral databases will improve sensitivity and throughput. Integration of machine-learning for deconvolution and prediction of extractable profiles could further streamline method development. Wider application to food, beverage, and medical device packaging is anticipated.

Conclusion

This study demonstrates a robust, multi-technique workflow for extractables and leachables analysis in medicine containers. By combining HR LC-MS, GC-MS, and ICP-MS with advanced data processing, it offers reliable identification, quantification, and compliance assessment of plastic additives and trace metals.

References

Comstock K., Bassey E., Schmelzel J. Identification and Quantitation of Plastic Additives in Medicine Containers by HR LC-MS, GC-MS and ICP-MS. Thermo Fisher Scientific, 2013.