Thermal Desorption – GCMS Method for Screening Analysis of Extractables in Drug Packaging Materials

Importance of the Topic

The evaluation of extractables and leachables in pharmaceutical packaging is critical for ensuring drug safety, efficacy, and regulatory compliance. Rapid screening methods support early detection of potential contaminants migrating into drug products.

Study Objectives and Overview

This study aims to establish a fast, solvent-free screening protocol using thermal desorption coupled with gas chromatography–mass spectrometry (TD-GCMS) to characterize volatile and semi-volatile extractables from ophthalmic solution packaging. Results are compared with leachable profiles obtained by liquid injection GCMS of the finished product.

Instrumentation

• GCMS system Shimadzu GCMS-QP2020 NX with TD-30 thermal desorption unit
• Column SH-Rxi-5Sil MS, 30 m × 0.25 mm ID, 0.25 μm film
• GC Conditions: linear velocity 44.4 cm/s, splitless injection, temperature program 50 °C hold 2 min then 10 °C/min to 320 °C hold 6 min
• MS Conditions: ion source 200 °C, interface 250 °C, scan 35–700 m/z
• TD Conditions: desorb tube 150 °C for 15 min, trap tenax TA at –20 °C, trap desorb 250 °C, transfer line 250 °C

Main Results and Discussion

Chromatographic profiles of LDPE bottle and nozzle were similar, while the HDPE cap showed increased hydrocarbon content. Fourteen extractables were detected and identified using NIST14 and a polymer additives library. Key findings include

• Residual solvent acetone detected in all components
• Plasticizers diethyl phthalate, diisobutyl phthalate, dibutyl phthalate present in all samples
• Breakdown products of antioxidants, lubricants, stabilizers and fire retardants such as 2-ethyl-1-hexanol, benzophenone, benzoic acid, naphthalene
• Decamethylcyclopentasiloxane indicating silicone lubricant residue

Leachables analysis of the ophthalmic solution revealed mostly drug-related peaks with only diethyl phthalate matching the extractable profile.

Benefits and Practical Applications of the Method

The TD-GCMS approach eliminates solvent extraction steps, reduces analysis time, and provides qualitative screening of volatile and semi-volatile impurities. It is particularly suitable for quality control and initial risk assessment of pharmaceutical packaging materials.

Future Trends and Opportunities

Advancements may include quantitative TD-GCMS methods, high-resolution mass spectrometry for greater sensitivity, automated sample handling, and application to a broader range of packaging polymers and dosage forms.

Conclusion

A straightforward thermal desorption GCMS protocol was developed for rapid screening of extractables in ophthalmic solution packaging. Detected compounds spanned plasticizers, additives and their degradation products. Correlation with leachable data supports its utility in ensuring drug safety.

References

1. Yu X, Wood D Analytical Testing – Extractables and Leachables Testing for Pharmaceutical Products Pharmaceutical Outsourcing Nov Dec 2017