Analysis of Extractables from Pharmaceutical Packaging Using Solvent Extraction GC-MS and Thermal Desorption GC-MS
MSTips No. 540
Pharmaceutical packaging materials come into direct contact with drug products and can affect drug quality through interactions. Leachables are compounds that move from packaging materials into a drug product under normal storage or use conditions. In contrast, Extractables are compounds released from packaging materials when they are exposed to harsh conditions, such as solvents or high temperatures. They are considered potential leachables. These compounds may include additives from the packaging materials, residues from the manufacturing process, and degradation products. Guidelines for risk management are provided by ISO 10993-18, USP <1663>, USP <1664>, and ICH Q3E. Examples include the identification of volatile compounds and solvent extractables by GC-MS. However, the analytical conditions are not clearly defined.
A comprehensive and accurate understanding of extractables is important for identifying potential chemical compounds that may affect drug quality. For compound identification in GC-MS analysis, commercial mass spectral databases (DBs) such as NIST are commonly used. However, some detected compounds are not registered in these DBs and are treated as unknown compounds. In 2021, our company released an “integrated analysis1)” software that combines NIST DB searching of mass spectra obtained by the electron ionization (EI) method with analysis of molecular ions in mass spectra obtained by the soft ionization (SI) method, enabling more reliable qualitative results. However, this analysis method is based on NIST DB searches, and the analysis of unknown compounds still remained a major challenge. To address this issue, we developed msFineAnalysis IQ Ver.3, which includes a structure estimation method based on deep learning-assisted mass spectrum prediction2) (AI Structure Analysis). (MSTips No. 535)
In this study, extractables from pharmaceutical packaging materials were analyzed by thermal desorption (TD)-GC-MS and solvent extraction GC-MS. The data were then analyzed using msFineAnalysis IQ Ver.3, and the results of the integrated analysis are reported here.