DEVELOPMENT AND VALIDATION OF CHIRAL HIGH-PERFORMANCE LIQUID-CHROMATOGRAPHIC METHODS FOR THE QUANTITATION OF VALSARTAN AND OF THE TOSYLATE OF VALINEBENZYL ESTER

A stereospecific HPLC method for the quantitation of CGP 49309 in samp les of its corresponding enantiomer valsartan has been developed and v alidated. The enantiomeric separation was achieved on a 5 mu m silica- bonded alpha(1)-acid glycoprotein column (Chiral AGP) with a phosphate buffer, pH 7, containing 2% (v/v) 2-propanol as a mobile phase. The l inearity was established in the range 0.1-4% (r>0.999). The limit of q uantitation was 0.1% and the limit of detection was 0.04%. The accurac y of the method was found to be 96.7% (average). For the precision (re peatability), a relative standard deviation value of 2.4% was found. S imilarly, a stereoselective HPLC method was also developed and validat ed for the quantitation of the enantiomer of the starting material use d for the synthesis of valsartan, namely (R)-valinebenzyl eater tosyla te. Baseline resolution of the enantiomers of valinebenzyl ester tosyl ate could be achieved on the chiral crown ether column Crownpak CR (Da icel) at 50 degrees C using water-methanol-trifluoroacetic acid (850:1 50:1, v/v) as a mobile phase. The linearity was established in the ran ge 0.5-5% (r>0.999). The accuracy of the method was found to be 100.5% (average). For the precision (repeatability), a relative standard dev iation value of 3.4% was found. Both methods were found to be suitable for the analysis of the respective analytes.