engleski

Purity assessment of recombinant human granulocyte colony-stimulating factor in finished drug product by capillary zone electrophoresis

Current methods for determination of impurities with different charge-to-volume ratio are limited especially in terms of sensitivity and precision. The main goal of this research was to establish a quantitativemethod for determination of impuritieswith charges differing from that of recombinant human granulocyte colony- stimulating factor (rhG-CSF, filgrastim) with superior precision and sensitivity compared to existing methods. A CZE method has been developed, optimized, and validated for a purity assessment of filgrastim in liquid pharmaceutical formulations. Optimal separation of filgrastim from the related impurities with different charges was achieved on a 50 m id fused-silica capillary of a total length of 80.5 cm. A BGE that contains 100 mM phosphoric acid adjusted to pH 7.0 with triethanolamine was used. The applied voltage was 20 kV while the temperature was maintained at 25°C. UV detection was set to 200 nm. Method was validated in terms of selectivity/specificity, linearity, precision, LOD, LOQ, stability, and robustness. Linearity was observed in the concentration range of 6– 600 g/mL and the LOQ was determined to be 0.3% relative to the concentration of filgrastim of 0.6 mg/mL. Other validation parameters were also found to be acceptable ; thus the method was successfully applied for a quantitative purity assessment of filgrastim in a finished drug product.

Capillary zone electrophoresis; Filgrastim; Purity; Recombinant human granulocyte colony-stimulating factor; Validation

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