Determination and Limits of Related Substances in Tamsulosin Hydrochloride
OBJECTIVE To establish a self-contrast HPLC method with correction factor for determination of the related substances in tamsulosin hydrochloride,and validate the limits of impurities based on the prediction of genotoxicity using Nexus 2.6 software(with Derek and Sarah).METHODS ZORBAX SB-C18(4.6 mm × 150 mm,3.5 μm)column was used for the determination of correction fac-tors of the eight known impurities in tamsulosin hydrochloride with mobile phase consisting of perchlorate buffer solution-acetonitrile by gradient elution under the detection wavelength of 225 nm,the related substances in tamsulosin hydrochloride were determine by self-con-trast HPLC method with the correction factor,and the genotoxicity of the impurities was predicted by using Nexus 2.6 software.RESULTS There was no significant difference(the deviation is within±0.02％)between the results by relative correction factors and external standards.The validation test showed that the proposed method met the requirements for the intended analytical applications,and the predicted result of impurity Ⅰ by Nexus 2.6 software was positive(ICH M7 class 3),and all the others were negative(ICH M7 class 5).CONCLUSION The established method is rapid,efficient,accurate and sensitive,and a limit of 0.1％is established for each known impurity according to the predicted genotoxicity.This study provides a basis for revising pharmacopoeia standards.
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