The impurity analysis and impurity method validation of montelukast sodium tablets

In the present work, the aim is to search appropriateness of impurities, which are taken reference from Q2(R1) Validation of Analytical Procedures: Text and Methodology and Montelukast Sodium Drug Master File, for film coated tablets and perform method validation.Mobile phase was acetonitrile and sodium dihydrogen phosphate (pH=3.7), UV-Vis detector was set at ? = 225 nm.At these chromatographic conditions, stationary phase experiments were done. Finally Symmetry C18,150x3.9mm,5µ column was selected because of it?s suitable structure for Montelukast Sodium. There was no interaction between column and active substance and there had no metal impurities in this column.In the method, recovery for Impurity A, Impurity B, Impurity C and Impurity D were with in the confidence limits. Linearities were obtained in the concentration range for all impurities, repeatabilities were calculated from the relative standart deviation of peak area values of the impurities.Recoveries were 126.9 % for 1-[[[(1R)-1-[3-[(1E)-2-(7-chloro-2-quinolinyl)ethenyl]phenyl]-3-[2-(1-hydroxy-1methylethyl)]phenyl]methyl] cyclopropane acetic acid(Impurity B) at LOQ level, 107.6 % for 1-[[[(1R)-1-[3-[(1E)-2-(7-choloro-2-quinolinyl)ethenyl]phenyl]-3-[1-hydroxy-1 methylethyl)phenyl]propyl]sulfinyl]methyl] cyclopropane acetic acid (Impurity C) at LOQ level, 101.5 % for 1-[[[(1R)-1-[3-[(1E)-2-(7-chloro-2-quinolinyl)ethenyl]phenyl]]-3-(2-carboxy)]phenyl]propyl]thio]methyl]- cyclopropane acetic acid disodium (Impurity A) at LOQ level, 102.6 % for 1-[[[(1R)-1-[3-[(1E)-2-(7-choloro-2-)ethenyl]phenyl]-3-[2-[1-(1- methyl)ethanyl)]phenyl]propyl]thio]methyl]cyclopropane acetic acid (Impurity D) at LOQ level and 98.1% for Montelukast Sodium at LOQ level.Linearity was obtained in the concentration range of 0.000005-0.003 mg/ml for all impurities. Repeatibilities were calculated from RDS of peak area values and were found as 0.82 for 1-[[[(1R)-1-[3-[(1E)-2-(7-chloro-2-quinolinyl)ethenyl]phenyl]-3-[2-(1-hydroxy-1-methylethyl)]phenyl]methyl] cyclopropane acetic acid (Impurity B) , 0.75 for 1-[[[(1R)-1-[3-[(1E)-2-(7-choloro-2-quinolinyl)ethenyl]phenyl]-3-[1-hydroxy-1methylethyl)phenyl]propyl] sulfinyl] methyl] cyclopropane acetic acid (Impurity C) ,0.81 for 1-[[[(1R)-1-[3-[(1E)-2-(7-chloro-2-quinolinyl)ethenyl]phenyl]]-3-(2-carboxy)]phenyl]propyl]thio]methyl]-cyclopropane acetic acid disodium (Impurity A) ,1.09 for 1-[[[(1R)-1-[3-[(1E)-2-(7-choloro?2-)ethenyl]phenyl]-3-[2-[1-(1-methyl)ethanyl)]phenyl]propyl]thio]methyl]cyclopropane acetic acid (Impurity D).The method was also performed by different analysts and on different instruments tests and the results were not different from each other at 99 % confidence level. In robustness tests it was observed that, the method was not influenced from varitions easily. For system suitability tests active subtance solution was injected to HPLC at 6 times and relative standart deviation (RSD) of the peak area was in accelerated degredation studies, impurities , the amount of the impurities were increased slightly but they remained in the limit of drug master file.As a result, it was observed that the method is selective enough for the determination of Montelukast Sodium impurities.