Determination of Class I USP Residual Solvents and TICs in Dietary Supplements and Pharmaceutical Products by GC/MS

Significance of the Topic

The presence of residual solvents in pharmaceutical and dietary supplement products can pose serious health and environmental risks. Regulatory frameworks such as USP <467> impose strict limits on Class I solvents due to their toxicity and potential carcinogenicity. Reliable and sensitive analytical techniques are essential for ensuring product safety and compliance.

Objectives and Study Overview

This application note demonstrates the determination of Class I USP residual solvents and the identification of total ion chromatogram (TIC) compounds in a vitamin dietary supplement, a pain reliever, and an allergy medication. The goal is to achieve simultaneous quantitation of target solvents at low ppm levels and screening of unknown volatiles in a single run.

Methodology and Instrumentation

Samples (250 mg of product in 25 mL water with sodium sulfate) were incubated in 20 mL headspace vials at 85 °C for 30 min. A 1 mL gas sample loop at 160 °C transferred the headspace to a gas chromatograph. GC separation used a BR-624ms capillary column (20 m × 0.18 mm × 1.0 µm) with a temperature program from 35 °C to 250 °C. The SCION SQ mass spectrometer operated in simultaneous full-scan (m/z 35–300) and SIM modes, employing Compound Based Scanning (CBS) for rapid method setup and optimized acquisition windows.

Used Instrumentation

• Bruker SHS-40 automated static headspace autosampler
• SCION SQ single quadrupole mass spectrometer
• BR-624ms GC column
• BR-1079 PTV injector with 3.4 mm split liner

Main Results and Discussion

Sensitivity experiments demonstrated clear detection of all Class I solvents at 0.1 ppm with excellent peak shapes and qualifier ions. Calibration curves yielded correlation coefficients (r2) above 0.999. No Class I residual solvents were found in any sample. However, full-scan data revealed other volatiles: borneol and terpenes in the multivitamin/weight-loss supplement, ethyl acetate and acetone (Class III solvents) in the allergy medication, and several unidentified TICs in the pain reliever. Automated library matching (reverse fit > 800) facilitated rapid identification of non-target compounds.

Benefits and Practical Applications of the Method

• Simultaneous quantitation of regulated solvents and screening of unknowns in one analysis
• Compound Based Scanning enables one-click method development from libraries
• Low detection limits support compliance with stringent regulatory thresholds
• Full-scan data provide quality-control insights into process contaminants or formulation impurities

Future Trends and Potential Applications

Advances may include integration of high-resolution MS for improved structural elucidation of TICs, expansion of screening libraries to cover Class II/III solvents and other volatiles, and implementation of automated data-analysis pipelines with machine learning for real-time contamination alerts.

Conclusion

The combination of the Bruker SHS-40 headspace sampler and SCION GC/MS with CBS offers a robust, sensitive, and efficient approach for residual solvent analysis. It ensures regulatory compliance for Class I solvents and enhances quality control by detecting non-target volatiles in pharmaceutical and supplement matrices.

References

1. USP <467> Chemical Tests: Organic Volatile Impurities, July 2007
2. Ed George, Application Notes #283030, Bruker Daltonics