Development and validation of rapid ion-chromatographic method with conductivity detection for trace level determination of allylamine in sevelamer drug substances.

A sensitive and rapid ion chromatography (IC) method was developed for the low level determination of allylamine (AAM) in sevelamer (SVM) drug substances, i.e., sevelamer hydrochloride (SVH) and sevelamer carbonate (SVC). This method utilized a Dionex Ion Pack CS14 IC column, a mobile phase of 10mM methane sulfonic acid with conductivity detection. The total chromatographic run time was as short as 8 min. The various factors involved in the sample preparation such as, extraction solvent, extraction time and stirrer speed were evaluated. This method was validated as per United States Pharmacopoeia (USP) and International Conference on Harmonization (ICH) guidelines in terms of detection limit, quantitation limit, linearity, precision, accuracy, specificity and robustness. Linearity of the method was very good over the concentration range of 9-750 μg/mL with the coefficient of determination (r(2)) 0.999. The detection and quantitation limit of AAM were 2.7 and 9.0 μg/mL, respectively. The recovery data obtained for AAM were between 97% and 109%. Also, the specificity of the method was proved through IC coupled with mass spectrometer (IC-MS). The developed method was found to be robust and applied successfully to determine the content of AAM in Sevelamer bulk drugs.