Thermal Desorption – GC/MS Method for Screening Analysis of Extractables in Drug Packaging Materials

Importance of the Topic

In pharmaceutical packaging, extractables and leachables (E&L) are key factors influencing drug safety, quality and efficacy. Extractables are compounds released from packaging under harsh conditions, while leachables represent those that migrate into the drug product under normal storage. Effective screening methods are essential to identify potential contaminants before products reach patients.

Goals and Study Overview

This study establishes a rapid screening workflow to profile extractables from ophthalmic solution packaging components (LDPE bottle and nozzle, HDPE cap) using thermal desorption–GC/MS and compares results to leachables detected in the drug solution by liquid injection GC/MS.

Methodology

Each packaging component was cut into small pieces (50 mg) and packed in a thermal desorption (TD) tube with glass wool. The sample was heated to 150 °C for 15 min, desorbing volatiles which were trapped on a Tenax® TA cold trap at –20 °C, then released at 250 °C and transferred to the GC/MS column. Leachables in the ophthalmic solution were analyzed by direct liquid injection into the same GC/MS system.

Used Instrumentation

• GCMS-QP2020 NX (Shimadzu)
• TD-30 Thermal Desorption Autosampler
• AOC-20i Plus/20s Plus Liquid Autosampler for leachables
• SH-Rxi™-5Sil MS column (30 m × 0.25 mm × 0.25 µm)

Main Results and Discussion

Chromatograms of LDPE bottle and nozzle were similar, dominated by hydrocarbons likely from lubricant wax. The HDPE cap released higher hydrocarbon levels. Key detected extractables included:

• Acetone (residual solvent)
• Plasticizers: diethyl phthalate (DEP), diisobutyl phthalate (DIBP), dibutyl phthalate (DBP)
• Plasticizer/additive breakdown products: 2-ethyl-1-hexanol, nonanal, benzophenone, benzoic acid, naphthalene, methyl stearate
• Siloxane (decamethylcyclopentasiloxane D5)

Only DEP was also observed as a leachable in the ophthalmic solution, confirming its migration under normal conditions.

Benefits and Practical Applications

The TD–GC/MS screening method is solvent-free, fast and requires minimal sample preparation, making it ideal for qualitative identification of a broad range of volatile and semivolatile extractables in polymeric packaging.

Future Trends and Potential Applications

Advances may include quantitative TD–GC/MS methods, integration with high-resolution mass spectrometry for improved identification, and expanding the approach to other dosage forms or barrier packaging materials.

Conclusion

A straightforward thermal desorption–GC/MS protocol was developed for rapid qualitative screening of extractables in ophthalmic packaging. Multiple plasticizers and additive degradation products were identified, and DEP was confirmed as the sole leachable in the drug solution. This workflow supports early risk assessment in packaging selection and product development.

References

1. Yu X., Wood D., “Analytical Testing – Extractables and Leachables Testing for Pharmaceutical Products,” Pharmaceutical Outsourcing, Nov/Dec 2017.
2. Wood A., “Extractables and Leachables Analysis of Pharmaceutical Products,” Outsourcing-Pharma, 2019.