Determination of Voriconazole Related Compound F in Voriconazole Using IC

Importance of the Topic

Voriconazole is a second-generation triazole antifungal approved for serious infections such as invasive aspergillosis.
Impurity control, particularly of voriconazole related compound F, is essential to meet ICH and USP thresholds (0.1%) in active pharmaceutical ingredients.

Objectives and Study Overview

The primary goal was to validate the USP monograph method for quantifying compound F in a 5 mg/mL voriconazole solution, achieving detection below 5 µg/mL (0.1%) and ensuring conformity with system suitability, sensitivity, and reproducibility criteria.

Instrumentation Used

• Thermo Scientific Dionex ICS-3000 IC system (single or dual pump, DC detector, AS autosampler).
• Dionex OmniPac PAX-100 Analytical Column (4×250 mm) with guard (4×50 mm).
• Dionex AMMS 300 Anion MicroMembrane suppressor, chemical regeneration mode.
• Thermo Scientific Chromeleon Chromatography Data System v7.1.

Methodology and Eluent Preparation

A manually prepared mobile phase of 1 mM NaOH in 25% methanol was used, degassed and confirmed for carbonate contamination. Electrolytic generation of 1 mM hydroxide via RFIC was also evaluated.
Samples were spiked at 0.5–10 µg/mL, injected (20 µL), and eluted at 1.0 mL/min, 40 °C, with suppressed conductivity detection.

Key Results and Discussion

• Separation achieved in under 12 minutes: compound F at ~6.4 min and chloride at ~9.8 min.
• System suitability: resolution ≥9.9 (>3.5 spec), tailing ≤1.2 (<2.0 spec), peak area RSD ≤2% (<10% spec).
• LOD/LOQ: 0.04 µg/mL and 0.1 µg/mL respectively, enabling detection at 0.002% in 5 mg/mL samples.
• Linearity demonstrated across 0.01–0.20% spiked range (r² >0.999).
• Robustness: method tolerance to ±10% temperature, column aging, and different eluent preparations, with all parameters within USP limits.
• RFIC-based hydroxide generation improved day-to-day retention time reproducibility.

Benefits and Practical Applications

The validated method provides high sensitivity and reliability for routine QC of voriconazole products.
Its fast analysis time and robust performance support compliance with pharmacopeial standards and reduce rework due to impurities.

Future Trends and Applications

Integration of reagent-free IC systems may streamline eluent preparation and further reduce variability.
Advances in column materials and suppression techniques will enhance resolution for other non-UV-active impurities.

Conclusion

The USP method for voriconazole related compound F determination by suppressed conductivity IC meets all regulatory specifications.
Sensitivity, repeatability, and robustness are demonstrated, supporting its use in pharmaceutical QC laboratories.

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