Rapid Determination of Cilostazol Impurity Ⅰ Correction Factor by qNMR-HPLC
OBJECTIVE To establish a quantitative nuclear magnetic resonance coupled with high performance liquid chromatog-raphy(qNMR-HPLC)technique for the rapid determination of cilostazol impurity Ⅰ correction factor.METHODS The mixture of cilostazol and cilostazol impurity Ⅰ was dissolved in deuterated dimethyl sulfoxide.A portion of the solution was determined by qNMR,while the other portion of the solution was diluted with water-acetonitrile(60∶40)and analyzed by HPLC.The correction factor of cilostazol impurity Ⅰ was calculated with the response signals from qNMR and the peak areas from HPLC.The correction factor of cilostazol impurity Ⅰ was also determined by HPLC standard curve method.A mixed solution containing residual solvent was prepared to simulate the effect of solvents in determining correction factors.When the content of cilostazol impurity Ⅰ was inaccurately assigned due to residual solvent,difference between qNMR-HPLC method and standard curve method was compared.RESULTS When the contents of cilostazol and cilostazol impurity Ⅰ were assigned accurately,the correction factors for cilostazol impurity Ⅰ by qNMR-HPLC method and HPLC standard curve method were 1.74 and 1.76,respectively,which were basically consistent with the pharmaco-poeial results.When cilostazol impurity Ⅰ contained residual solvents,and there was an error in the content assignment,the correction factor of the determination by the qNMR-HPLC technique was still l.72,and the result was not affected by the accuracy of the content.While the correction factor of HPLC standard curve was 2.01,which was deviated from the actual results.CONCLUSION Com-pared with the HPLC standard curve method,the qNMR-HPLC coupling technique is independent of the accuracy of the content of the substance to be measured and the weighing volume,and does not require purification to prepare a high purity compound.qNMR-HPLC is a powerful tool in the determination of impurity correction factors.
quantitative nuclear magnetic resonanceHPLCcoupling techniquecilostazolcilostazol impurity Ⅰcorrection factor
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