Premium
Purity assessment of recombinant human granulocyte colony‐stimulating factor in finished drug product by capillary zone electrophoresis
Author(s) -
Benković Goran,
Škrlin Ana,
Madić Tomislav,
Debeljak Željko,
MedićŠarić Marica
Publication year - 2014
Publication title -
electrophoresis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.666
H-Index - 158
eISSN - 1522-2683
pISSN - 0173-0835
DOI - 10.1002/elps.201300552
Subject(s) - filgrastim , chromatography , capillary electrophoresis , chemistry , capillary action , linearity , detection limit , impurity , analytical chemistry (journal) , materials science , physics , organic chemistry , toxicity , quantum mechanics , neutropenia , composite material
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 quantitative method for determination of impurities with charges differing from that of recombinant human granulocyte colony‐stimulating factor (rh G ‐ 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 μm 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 μg/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.