EXTRACTABLES AND LEACHABLES: A COMPLEX ANALYSIS

Importance of the Topic

Extractables and leachables analysis is critical to evaluate potential chemical migration from packaging materials into pharmaceutical products. Regulatory compliance and patient safety depend on sensitive and accurate detection of compounds such as plasticizers adhesives and degradation products. This evaluation ensures product integrity during processing storage and administration.

Objectives and Study Overview

The study aims to demonstrate a streamlined workflow for identification and quantification of extractable and leachable compounds using the Agilent Intuvo 9000 GC coupled with a high efficiency source mass spectrometer. It compares method sensitivity robustness and ease of use when analyzing phthalate standards and real sample extracts from lidocaine transdermal patches and polymeric backing.

Methodology

The analytical approach combines aggressive solvent extraction to simulate worst case migration with routine conditions reflecting actual exposure. Sample preparation and detection modes include

• Phthalate standards diluted to 500 ppb 50 ppb and 5 ppb analyzed in selected ion monitoring mode
• Dichloromethane extracts of 5 percent lidocaine transdermal patches and film backing evaluated in full scan mode

Instrumentation Used

The analysis was performed on an Agilent Intuvo 9000 gas chromatograph with a high efficiency source mass spectrometer. A 30 meter Intuvo HP 5ms Ultra Inert column operated at a flow rate of 1 mL per minute provided chromatographic separation. The compact design and inert flow path simplify operation and maintain data quality.

Main Results and Discussion

Selected ion monitoring detected six common phthalates down to 5 ppb with sharp symmetric peaks confirming method sensitivity. Extracts from the transdermal patch revealed the active ingredient lidocaine and preservatives methylparaben and polyparaben at high levels and bis2 hydroxyethyl terephthalate at trace levels. Film backing extracts showed minor amounts of lidocaine and parabens consistent with surface contact and also contained terephthalate.

Benefits and Practical Applications

This method offers

• High sensitivity for low level phthalate quantification
• Reproducible peak shapes through an inert simplified flow path
• Efficient sample throughput with easy column installation and compact footprint
• Comprehensive profiling of active inactive and potential leachable compounds in a single analysis

This workflow supports quality control regulatory submissions and product compatibility assessments.

Future Trends and Potential Applications

Future developments may include high resolution mass spectrometry for unknown identification automated data processing for rapid reporting and expanded compound libraries for polymer additives. Modular compact GC systems with user friendly interfaces will further increase laboratory efficiency and facilitate compliance across industries.

Conclusion

The Agilent Intuvo 9000 GC with MS HES and Ultra Inert HP 5ms column provides an integrated solution for extractables and leachables analysis. Its sensitivity robustness and streamlined operation enable comprehensive assessment of packaging and pharmaceutical materials.

References

1. Wong DM Firor RL Analysis of Extractable Leachable Compounds from Transdermal Patches Using GC MSD Systems Agilent Technologies Application Note publication number 5991 5605EN 2015
2. Multiresidue Pesticide Analysis Improving Peak Shape Consistency Agilent Technologies publication number 5991 7175EN 2016