How SGS cut their extractables and leachables workflow time in half using high-resolution analytical methods

Importance of the Topic

Extractables and Leachables (E&L) testing is critical to ensure that pharmaceutical drug products and medical devices do not release harmful substances during manufacturing, storage, or use. It safeguards patient safety, supports regulatory compliance, and preserves the stability and efficacy of active pharmaceutical ingredients.

Objectives and Study Overview

The primary objective was to evaluate how high‐resolution analytical methods could accelerate E&L workflows and enhance data quality at the SGS Health Science facility in Fairfield, New Jersey. The case study details the sequential technology upgrade across non-volatile, volatile/semi-volatile, and elemental impurity testing platforms and assesses their impact on sensitivity, resolution, and throughput.

Methodology and Instrumentation

Sample Preparation and Protocols:

• Non‐selective extraction workflows to capture volatile, semi-volatile, non-volatile, and elemental impurities from various matrices.
• Unbiased methods that minimize the risk of missing unknown analytes.

Analytical Instruments:

• Liquid Chromatography–Mass Spectrometry (LC-MS): Thermo Scientific Q Exactive Plus Hybrid Quadrupole-Orbitrap.
• Gas Chromatography–Mass Spectrometry (GC-MS/MS): Thermo Scientific Q Exactive GC Orbitrap with headspace and direct injection capabilities.
• Elemental Impurity Testing: Inductively Coupled Plasma Spectroscopy (ICP) and ICP-MS.

Main Results and Discussion

Unknown Identification and Selectivity:

• High‐resolution accurate mass (HRAM) detection enabled confident assignment of unknown compounds without sole reliance on limited spectral libraries.
• All‐ion fragmentation (AIF) in LC-MS and electron/chemical ionization (EI/CI) in GC-MS provided detailed fragment data for structural elucidation.

Sensitivity and Dynamic Range:

• Detection limits improved from ppm to sub‐ppb levels, ensuring trace impurities are reliably quantified.
• Intrascan dynamic range exceeded four orders of magnitude, allowing simultaneous detection of low‐abundance and high‐concentration species.

Throughput Enhancements:

• Parallel acquisition of positive and negative polarity in a single LC-MS sequence halved analysis time.
• Rapid polarity switching and full‐scan data capture eliminated the need for re-analysis and enabled retrospective data review.

Benefits and Practical Applications

Operational Efficiency:

• Overall E&L workflow times reduced by 50%, doubling sample throughput.
• Streamlined data processing and protocol troubleshooting using Chromeleon Chromatography Data System.

Data Quality and Confidence:

• High resolving power removed isobaric interferences, improving quantitation accuracy in complex sample matrices.
• Accurate mass measurements support precise toxicological risk assessments and regulatory reporting.

Business Impact:

• Faster project completion opened capacity for additional contracts, generating new revenue streams.
• Enhanced technical capabilities provided a competitive edge in the CRO marketplace.

Future Trends and Opportunities

Continuous regulatory evolution will drive demand for even more sensitive and selective E&L methodologies. Integrating automation, advanced data analytics, and AI‐assisted spectral interpretation may further shorten turnaround times. Ongoing collaboration with instrument vendors and interdisciplinary teams will facilitate rapid adaptation to new standards and emerging analytical challenges.

Conclusion

The implementation of high‐resolution Orbitrap MS and upgraded GC-MS/MS and ICP systems at the SGS Health Science Fairfield facility significantly improved sensitivity, selectivity, and productivity for E&L testing. By halving workflow times and achieving sub-ppb detection limits, the laboratory enhanced operational efficiency, data confidence, and its competitive position in the pharmaceutical and medical device testing market.