DETERMINATION OF RESIDUAL CHLORIDE IN SEVELAMER CARBONATE USING HIGH PERFORMANCE LIQUID CHROMATOGRAPHY

Abstract

Sevelamer carbonate is the active ingredient of Renvela tablets; a cross-linked polymeric amine that binds phosphate. It was developed as a pharmaceutical alternative to sevelamer hydrochloride (Renagel). Renvela is indicated for the control of hyperphosphatemia in patients with end-stage renal disease (ESRD). Sevelamer carbonate is manufactured from sevelamer hydrochloride, in which carbonate replaces chloride as the counter ion. Therefore, chloride is one of the impurities present in sevelamer carbonate. A number of suitable analytical techniques are available for chloride estimation, including titration, colorimetry, electrochemical chromatography, indirect photochemical detection, and ion chromatography. Limits of detection range from 50 g/L for colorimetry to 5 mg/L for titration. The specification limit of chloride content in sevelamer carbonate is not more than 0.05%. As a result, accurate determination of this residual chloride in sevelamer carbonate is not possible with colorimetry and titration. In the case of electrochemical detectors, the electrode response could drift with time. Indirect photometric detection is a more time consuming method. A novel isocratic reverse phase HPLC method has been developed in order to detect and quantify the residual chloride. This method involves mixing the drug (polymer) with water, filtering off the solution, and quantitating the water soluble chloride by HPLC using refractive index detector. The method was validated with respect to specificity, precision, linearity, and robustness. The presented method provides equal sensitivity with ion chromatography, specific, and inexpensive analytical procedure and, therefore, is highly suitable for detection and quantification of the residual chloride in sevelamer carbonate API.