SENSITIVE LIQUID CHROMATOGRAPHIC METHODS FOR THE DETERMINATION OF GENOTOXIC IMPURITIES IN LETROZOLE

Sensitive liquid chromatographic methods for the determination of two genotoxic impurities, namely hydrazine hydrate and 4-bromomethyl benzonitrile, in letrozole have been presented. Method-A is the pre-column derivative UFLC method for the determination of hydrazine hydrate with 4-methoxy benzaldehyde in letrozole. The chemistry involved in the derivatization is explained with suitable mechanism. Method-B offers the determination of 4-bromomethyl benzonitrile in letrozole. Both the methods were validated as per International Conference on Harmonization guidelines. Correlation coefficient values were found to be about 0.99. The % recoveries of the added impurities were found around the ranges of 94.2 to 94.6 for method-A and 92.5 to 100.5 for method-B.