Analysis of Extractables from Pharmaceutical Packaging Materials by Solvent Extraction-GC-MS and Headspace-GC-MS

Importance of the Topic

Interactions between pharmaceutical products and packaging materials can lead to the formation of extractables and leachables, posing safety risks. Thorough analysis of these compounds is essential to ensure drug quality, regulatory compliance, and patient safety.

Objectives and Study Overview

This study aims to systematically identify volatile and semi-volatile compounds extractable from PVC-based pharmaceutical packaging using both solvent extraction and high-temperature headspace extraction combined with GC-MS. It also evaluates the efficacy of the Polymer Additives Library for rapid and accurate compound identification.

Methodology and Instrumentation

Analyses employed a Shimadzu GCMS-QP2020 NX equipped with an AOC-20is autosampler for solvent injection and an HS-20 for headspace sampling, using an SH-I-5MS column. Solvent extraction used hexane, dichloromethane, and ethanol with ultrasonic treatment followed by static extraction; high-temperature extraction applied headspace sampling at up to 250 °C without solvents. GC conditions included splitless or split injections, helium carrier at constant linear velocity, and an oven program from 40 °C to 330 °C. MS detection was by electron ionization in scan mode (m/z 29–800).

Key Results and Discussion

Solvent extraction identified a range of plasticizers including tris(2-ethylhexyl)trimellitate (TOTM), di(2-ethylhexyl)phthalate (DEHP), di(2-ethylhexyl)adipate (DEHA), and lubricants such as fatty acids and esters. Extraction efficiency varied with solvent polarity: nonpolar solvents preferentially extracted low-polarity additives, whereas ethanol favored polar components. High-temperature headspace extraction at 250 °C maximized peak detection, revealing not only parent additives but also their thermal decomposition products (e.g., degradation fragments of TOTM and PVC). Use of the Polymer Additives Library with retention indices enabled accurate identification of both additives and decomposition products, outperforming general-purpose libraries.

Benefits and Practical Applications

• Solvent extraction offers broad compound coverage across a wide polarity range.
• High-temperature headspace sampling provides rapid, solvent-free analysis with minimal sample preparation.
• Specialized Polymer Additives Library enhances specificity and confidence in identifying packaging-related compounds and degradation products, supporting robust risk assessment in pharmaceutical QA/QC.

Future Trends and Opportunities

Advances in mass spectral databases and data-processing algorithms will further streamline extractables profiling. Emerging high-resolution MS techniques and predictive computational models will enhance sensitivity and selectivity. Regulatory harmonization under initiatives like ICH Q3E will drive standardized guidelines, while the rise of single-use disposable technologies will require continued development of rapid, robust screening methods for complex biologic formulations.

Conclusion

Combining solvent and high-temperature headspace GC-MS with specialized mass spectral libraries enables comprehensive and efficient screening of extractables from pharmaceutical packaging. This integrated approach supports improved safety evaluations and regulatory compliance, facilitating the development and quality control of drug products.