Method Development and Method Validation for Residual Water Determination of Erythropoietin Pharmaceutical Formulations by Volumetric Karl Fischer Titration
Keywords:
Erythropoietin, Lyophilized powder, Method validation, Residual water determination, Volumetric Karl Fischer titrationAbstract
The aim of this study is to develop and validate a water determination method for erythropoietin products using volumetric Karl Fischer (KF) titration technique. The external extraction technique using Hydranal™ formamide dry as an extraction solvent and using a mixture solution of Hydranal™ methanol dry and Hydranal™ formamide dry in a ratio of 60:40 as a solvent in the titration vessel was designed as a suitable method. The developed method was validated for specificity, repeatability, accuracy, and intermediate precision. The method was specific to the residual water contained in the erythropoietin pharmaceutical products as there was no effects from any interferences. Repeatability expressed the relative standard deviation (RSD) of six replicate samples as 4.6% (≤10%), which clearly revealed that the method was precise. The %recoveries obtained from three concentration points (lowest %residual water content, 100% and 120% of specification) were 101%, 104% and 105%, which were within the acceptable range of 90-110%. It obviously indicated that the method provided a very acceptable accuracy. The intermediate precision outcomes on different days and between analysts were shown in terms of %margin. %Margin was observed as an excellent value of 6% (≤25%). This indicated that the method was reproducible. In conclusion, it was indicated that the developed method was suitable for water determination in erythropoietin products since the validation results show that the method was specific, precise, accurate, and reproducible.
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