Monitor Organic Volatile Impurities (OVIs) in Pharmaceutical Products, Using Solid Phase Microextraction/Capillary GC

Importance of the Topic

Monitoring organic volatile impurities (OVIs) in pharmaceutical products is crucial for ensuring safety, efficacy and regulatory compliance. Trace levels of residual solvents or volatile contaminants can affect drug purity, patient health and stability. A rapid, sensitive and solvent-free approach supports routine quality control and aligns with green analytical practices.

Objectives and Study Overview

The primary goal of the study was to evaluate solid phase microextraction (SPME) coupled with capillary gas chromatography (GC) for screening OVIs in water-soluble drug substances. Chemists at Hoffmann-La Roche compared headspace versus immersion SPME sampling modes under United States Pharmacopeia <467> guidelines for key solvents including benzene, chloroform, 1,4-dioxane, methylene chloride and trichloroethylene.

Methodology and Instrumentation

• SPME fibers

• 100 µm polydimethylsiloxane (PDMS) for nonpolar analytes
• 85 µm polyacrylate for polar analytes (e.g., alcohols)

• Sampling modes: headspace and immersion (15 min extraction; 1 min desorption)
• GC column: 75 m × 0.53 mm ID, 3 µm film (6 % cyanopropylphenyl/94 % PDMS)
• Oven program: 40 °C (35 min) → 220 °C at 40 °C/min (5 min hold)
• Carrier gas: helium at 35 cm/s; Detector: FID at 80 °C; Injection: splitless, 200 °C, 3 min hold

Main Results and Discussion

• Detection limits ranged from 0.002 µg/mL (benzene) to 0.3 µg/mL (1,4-dioxane in immersion mode).
• Precision (RSD) was typically below 3 % for most solvents and below 7 % for ethanol in headspace mode.
• Headspace SPME prolonged fiber lifetime and provided higher sensitivity for analytes present mainly in vapor phase. Immersion SPME was more sensitive for analytes dissolved in the liquid.
• Combining both modes offers a complementary approach to selectively target more or less volatile compounds.

Benefits and Practical Applications

SPME/GC delivers a fast, solvent-free workflow that minimizes sample preparation, reduces operational costs and eliminates organic solvent hazards. The technique provides consistent precision over wide concentration ranges, making it well suited for routine screening and quantitative analysis in pharmaceutical QC and R&D laboratories.

Future Trends and Potential Applications

• Development of novel fiber coatings with enhanced selectivity and durability
• Integration of automated SPME autosamplers for high-throughput screening
• Coupling with mass spectrometry for expanded analyte identification and quantitation
• Application to complex biologics, environmental and food matrices

Conclusion

SPME combined with capillary GC presents an efficient, sensitive and environmentally friendly solution for monitoring OVIs in pharmaceutical products. The complementary use of headspace and immersion sampling optimizes detection across a range of compound volatilities, supporting regulatory compliance and operational efficiency.

References

1. Rosen Shaw S., Smith A.-M., Nelson L.C., Scypinski S., poster presentation, AAPS Conference, 1994.
2. Yang X., Peppard T., J. Agric. Food Chem. 42:1925–1930 (1994).
3. Zhang Z., Pawliszyn J., Anal. Chem. 65:1843–1852 (1993).