Automated and Simultaneous Identification and Quantification in Extractables and Leachables Analysis

Significance of the topic

Extractables and leachables analysis is critical to ensure the safety of medical devices, food packaging and pharmaceuticals. Accurate detection and quantification of potential contaminants are essential for regulatory compliance and patient protection.

Objectives and overview of the study

This study evaluates a complementary GC/MS and Cerno Polyarc-FID configuration combined with Cerno MassWorks spectral calibration to achieve simultaneous identification and universal quantification of unknown analytes using a single calibration standard.

Methodology and instrumentation

• Sample preparation included a test mixture of common E&L compounds at unknown concentrations and five-level calibration curves of surrogate molecules.
• Gas chromatograph: Agilent 7890A with split ratio 50/50 via helium-purged splitter to both Agilent 5973 quadrupole MS and Cerno Polyarc-FID.
• GC conditions: split ratio 10:1, inlet temperature 300°C, column flow 2.6 sccm, oven program from 40 °C (5 min) to 275 °C at 15 °C/min.
• MS conditions: electron ionization at 70 eV, scan range 33–500 m/z, source 230 °C, quadrupole 150 °C, transfer line 250 °C.
• FID and Polyarc reactor: reactor setpoint 293 °C, hydrogen flow 35 sccm, air flow 2.5 sccm, makeup helium 5 sccm for complete conversion of organics to methane.
• Data analysis: Cerno MassWorks software calibrated raw MS spectra for improved mass accuracy and automated identification of unknowns.

Main results and discussion

• MS quantification with surrogate compounds yielded large errors (2–71%) and non-uniform response factors dependent on functionality and retention time.
• Polyarc-FID provided a uniform response per mole of carbon over seven orders of magnitude, achieving quantification errors below 10% and reproducibility under 2% RSD using a single internal standard.
• The helium-purged splitter allowed simultaneous MS identification and Polyarc quantification in a single injection.
• MassWorks calibration enhanced identification of compounds absent from standard libraries by delivering accurate mass and spectral accuracy matches.

Benefits and practical applications

• Streamlines workflow by eliminating multiple calibration curves and the need for extensive surrogate selection.
• Improves accuracy, reproducibility and lowers detection limits by approximately 30-fold for certain additives.
• Applicable to QA/QC laboratories in pharmaceutical manufacturing, medical device production and food packaging industries.

Future trends and opportunities

Advancements in detector technology, high-resolution mass spectrometry and data automation will further enhance extractables and leachables workflows.

• Expansion of universal carbon quantification approaches to diverse analytical platforms.
• Development of real-time or in-line monitoring systems for leachable compounds.
• Integration of machine learning for automated spectral deconvolution and predictive risk assessments.

Conclusion

The GC/MS-Polyarc-FID setup combined with MassWorks calibration offers a robust, accurate and efficient solution for extractables and leachables analysis, reducing calibration burden while ensuring regulatory compliance and safety assurance.

Reference

• Tommy Saunders, Andrew Jones, Ashley Baeten, Nikki Carlson, Owen Boldt and Yongdong Wang. Automated and Simultaneous Identification and Quantification in Extractables and Leachables Analysis. Activated Research Company and Cerno Bioscience.