Simple and Accurate Analysis of Extractables from Pharmaceutical Packaging Materials using Headspace GC-MS and Special Mass Spectral Library for Additives

Significance of the Topic

Pharmaceutical packaging materials such as PVC-based film can release chemical compounds into drug products under typical and high-temperature conditions. Accurate profiling of these extractables ensures patient safety and regulatory compliance, particularly in parenteral and inhalation formulations where leachables pose heightened risk.

Objectives and Study Overview

This study compares solvent extraction followed by liquid injection GC–MS (LI–GC–MS) with headspace GC–MS (HS–GC–MS) under elevated temperatures to develop a streamlined workflow for detecting a broad range of packaging-derived additives and their degradation products.

Methodology and Instrumental Setup

Sample preparation involved:

• Solvent extraction of cut PVC bag fragments (400 mg) in ethanol, dichloromethane and hexane, sonicated for 5 h, then stored 3 days.
• Headspace extraction of similar samples sealed under nitrogen and heated at 80–250 °C in HS vials.

Instrumental setup:

• Liquid injector: AOC-20i;
• Headspace sampler: HS-20;
• GC–MS system: Shimadzu GCMS-QP2020 NX with SH-I-5ms column (30 m × 0.25 mm, 0.25 µm).
• Mass spectra acquired in scan mode (m/z 29–800).
• Compound identification using NIST and Shimadzu Polymer Additives libraries with retention index matching.

Main Results and Discussion

Solvent extraction identified a wide range of plasticizers (TOTM, DEHP, DEHA) and lubricants (palmitic and stearic acids, ethyl palmitate). High-temperature HS–GC–MS yielded simpler chromatograms, with optimal extraction at 250 °C, selectively releasing key plasticizers and thermal decomposition products of TOTM. The Polymer Additives Library enabled confident annotation of additives and their breakdown compounds.

Benefits and Practical Applications

The combined approach offers:

• Comprehensive coverage of diverse extractables via multiple solvents.
• Rapid screening with HS–GC–MS for routine QC.
• Enhanced identification accuracy using specialized additive libraries.

Future Trends and Applications

Integration of high-resolution mass spectrometry and advanced spectral libraries will further improve detection sensitivity and specificity. Automation of sample processing and data analysis pipelines can accelerate extractables profiling for new packaging materials and support regulatory submissions.

Conclusion

This study demonstrates that HS–GC–MS at elevated temperatures, complemented by solvent extractions, provides a robust, efficient, and accurate strategy for characterizing extractables in pharmaceutical packaging. The use of dedicated polymer additive libraries enhances compound identification, meeting industry demands for patient safety and compliance.

Reference

1. FDA Guidance for Industry: Container Closure Systems for Packaging Human Drugs and Biologics.