Organic Volatile Impurities in Pharmaceutical Products: Selectivity of Capillary GC Columns

Importance of the Topic

Residual organic solvents in pharmaceutical products pose health risks and are tightly regulated. Capillary gas chromatography (GC) is a critical analytical technique for detecting and quantifying these volatile impurities to ensure safety and compliance.

Objectives and Study Overview

This study compares the selectivity of three capillary GC columns recommended by USP <467> and the European Pharmacopoeia. The goal is to assess their ability to separate five regulated organic volatile impurities (OVIs) and a broader set of 42 common solvents used in pharmaceutical processing.

Methodology

Temperature programming from 40 °C (5 minutes) to 200 °C at 2 °C/min was applied. Helium carrier gas at 35 cm/s and split injection (100:1) of a 0.2 µL neat solvent mix ensured reproducible retention. A flame ionization detector (FID) at 250 °C provided universal detection.

Used Instrumentation

• Gas chromatograph with FID at 250 °C
• SPB-5 column: 5% phenyl-95% methylpolysiloxane, 30 m × 0.53 mm ID, 5.0 µm film
• OVI-G43 column: 6% cyanopropylphenyl-94% dimethylpolysiloxane, 30 m × 0.53 mm ID, 3.0 µm film
• SUPELCOWAX 10 column: polyethylene glycol, 30 m × 0.53 mm ID, 1.0 µm film

Main Results and Discussion

• SPB-5 and OVI-G43 provided comparable elution for the five regulated OVIs, governed largely by boiling point and dispersive interactions.
• SUPELCOWAX 10 exhibited distinct elution order shifts and higher resolution for many solvents, due to polar interactions and hydrogen bonding.
• Key interaction types influencing selectivity included dispersive, dipole-dipole, dipole-induced dipole, π-π, and hydrogen bonding, corresponding to analyte polarity and functional groups.
• A dual-column approach using OVI-G43 and SUPELCOWAX 10 resolved all 42 tested solvents, offering robust confirmation of solvent identity.

Benefits and Practical Applications

• Enables accurate quantification of USP and prospective European Pharmacopoeia residual solvents for quality control and regulatory compliance.
• Allows selection of the most appropriate column phase based on solvent chemistry for routine and confirmatory analyses.
• Dual-column strategies increase confidence in identification and reduce coelution issues, improving data reliability.

Future Trends and Potential Applications

• Design of novel stationary phases with enhanced selectivity for emerging impurities.
• Integration of automated dual-column systems for high-throughput pharmaceutical testing.
• Coupling GC with mass spectrometry for trace-level detection and definitive compound confirmation.

Conclusion

While SPB-5 and OVI-G43 meet USP <467> requirements for analyzing regulated OVIs, SUPELCOWAX 10 offers orthogonal selectivity and superior resolution for a wider range of solvents. Implementing complementary column techniques ensures comprehensive and reliable volatile impurity analysis in pharmaceutical quality control.

References

• The United States Pharmacopeia and The National Formulary USP 23–NF18, USP Convention 1995, <467> Organic Volatile Impurities, pages 1746–1748