Determination Of Organic Impurities In Tadanafil

Tadalafil is mainly used for erectile dysfunction(ED).Organic impurities in tadalafil may occur during the production or storage of APIs,which are ineffective and potentially toxic for treatment,so the profile of Tadalafil organic impurities is analyzed and studied.Technological research,impurity control,formulation of quality standards and establishment of highly sensitive determination methods for known impurities TAD-I,TAD-II,methylamine and unknown impurities are of great significance for impurity research of tadanafil.The known impurities TAD-I,TAD-II and unknown impurities were determined by high performance liquid chromatography(HPLC),while methylamine was determined by post-derivatization high performance liquid chromatography(RP-HPLC).Both methods have high sensitivity,accuracy and precision,which can effectively control the quality of Tadanafil and reduce the risk of drug use.The results show that the content of TAD-I,TAD-II and unknown impuritiesin Tadalafil was determined by high performance liquid chromatography(HPLC).The linear correlation coefficient(r)of TAD-I was 0.999 at the concentration range of0.1431-1.1446 μg/m L,the quantitative limit(QL)was 0.15 μg/m L,the detection limit(DL)was 0.0477 μg/m L,and the recovery was close to 100% at the range of 0.15-1.2μg/m L.The relative standard deviation(RSD)of repeatability test was 0.6%,and the relative standard deviation(RSD)of intermediate precision test was 0.7%.The linear correlation coefficient(r)of TAD-II was 1.000 at the concentration range of0.1499-1.1992 μg/m L,the quantitative limit(QL)was 0.15 μg/m L,the detection limit(DL)was 0.0500 μg/m L.The recovery was close to 100% at 0.15-1.2 g/m L.The relative standard deviation(RSD)of precision test was 1.0%,and the relative standard deviation(RSD)of intermediate precision test was 0.6%.The linear correlation coefficient(r)of unknown impurities was 1.000 at 0.1499-1.1992 g/m L,and the quantitative limit(QL)was 0.15 g/m L.The limit(DL)is 0.0335 g/m L.The analytical method is accurate,stable and reliable,and can effectively quantify the contents of TAD-I,TAD-II and unknown impurities.Benzoyl chloride derivatization-HPLC method of methylamine content of Tadalafil,the solution was stable at 15℃ for 24 hours.The linearity coefficient of correlation was 0.989 at the range 0.1154-0.7690 μg/m L of methylamin content in Tadalafil.The quantitative limit(QL)was 0.1154 μg/m L,the detection limit(DL)was0.0385 μg/m L.The average recovery of QL spike sample solution was 112.9%,100%spike sample solution was 125.4%,120% spike sample solution was 118.8%,and the relative standard deviation(RSD)for precision was 13.3%,and the relative standard deviation(RSD)of intermediate precision test was 6.7%.The analytical method is accurate,stable and reliable,and it can effectively quantify the content of methylamine in Tadalafil.