The present method gives a detailed description for the development and validation of a simple stability indicating reverse phase liquid chromatographic method for 10-hydroxycamptothecin(10-HCTN) in the presence of it...The present method gives a detailed description for the development and validation of a simple stability indicating reverse phase liquid chromatographic method for 10-hydroxycamptothecin(10-HCTN) in the presence of its impurities namely Imp A and Imp B along with degradation products generated from forced degradation studies. The drug was subjected to stress conditions of hydrolysis (acid, base and neutral), oxidative, photolytic and thermal stress degradation. Degradation was observed when subjected to treatment with peroxides or under conditions normally used for typical acid and base hydrolysis. The drug was found to be stable under other stress conditions attempted such as photolytic and thermal. Successful separation and isolation of the drug from related impurities and degradation products formed under stress conditions was achieved on an Inertsil ODS-3V (250 mm × 4.6 mm, 5 μm) column using a phosphate buffer, acetonitrile, methanol and Nanopure water. The developed HPLC method was validated with respect to specificity, linearity, accuracy, precision, sensitivity, robustness and solution stability. The assay method was found to be linear in the range of 0.16 mg/mL to 0.24 mg/mL with a correlation coefficient of 0.999 and the linearity of the impurities was established from 0.02% (LOQ) to 0.3%. Recoveries of assay and impurities were found between 99.4% and 100.3%. The developed HPLC method can be used to determine the related substances and assay determinations of 10-HCTN and also to evaluate the quality and long term stability of production samples.展开更多
The present method provides the detailed description of development and validation of a simple stability indicating re- verse phase column liquid chromatographic method for Olmesartan in the presence of its impurities...The present method provides the detailed description of development and validation of a simple stability indicating re- verse phase column liquid chromatographic method for Olmesartan in the presence of its impurities namely Imp-A, Imp-B, Imp-C, Imp-D, Imp-E, Imp-F and Imp-G and degradation products generated from forced degradation studies. The drug substance was subjected to stress conditions of aqueous hydrolysis, Oxidative, photolytic and thermal stress degradation. The degradation of Olmesartan was observed under acid hydrolysis, base hydrolysis and peroxide. The drug was found to be stable to other stress conditions attempted. Successful separation of the drug from synthetic impu- rities and degradation products formed under stress conditions was achieved on symmetry C18, 150 mm × 4.6 mm, 5μ column using a phosphate buffer, Acetonitrile and Milli Q water. The developed LC method was validated with respect to specificity, linearity, accuracy, precision, raggedness and robustness. The assay method was found to be linear in the range of 250 μg?mL–1 to with 1000 μg?mL–1 correlation coefficient of 0.9999 and the linearity of the impurities was es- tablished from LOQ to 0.4%. Recoveries of assay and impurities were found between 98.5% and 101.2%. The devel- oped LC method to determine the related substances and assay determinations of Olmesartan can be used to evaluate the quality of regular production samples and stability samples. To best of our knowledge, the validated stability indi- cating LC method which separates all the impurities disclosed in this investigation was not published elsewhere.展开更多
Budesonide is a corticosteroid used for the treatment of asthma via various matrices and inhalation mechanisms. An unknown peak of Budesonide aqueous formulation has been investigated during stability study wherein th...Budesonide is a corticosteroid used for the treatment of asthma via various matrices and inhalation mechanisms. An unknown peak of Budesonide aqueous formulation has been investigated during stability study wherein the impurity level observed around 0.1% well below the threshold 0.5%. The approach to identify anonymous species was adopted as first to generate the impurity in sample, isolate, enrich and was subjected to LC-MS/MS and NMR for spectral studies. Based on the spectral data the anonymous species were identified as a “Lumibudesonide’’ ((5aR,5bS,5cS,6S,7aS,7bS,10aR,11aS,11bS)-6-hydroxy-7b-(2-hydroxyacetyl)-5b,7a-dimethyl-9-propyl 1,5a,5b,5c,6,7,7a,7b,10a,11,11a,11b dodecahydrocyclopenta[2'',3'']cyclopropa [1'',2'':3', 4']benzo [1',2':4,5]indeno [1,2-d][1,3]dioxol-5(2H)-one), which is observed in photolysis of Budesonide.展开更多
Arformoterol (R, R) is an enantiomer of racemic formoterol, was the first long-acting beta agonist (LABA), approved by U.S. food and Drug Administration (FDA). The Arformoterol which is used for the treatment of Chron...Arformoterol (R, R) is an enantiomer of racemic formoterol, was the first long-acting beta agonist (LABA), approved by U.S. food and Drug Administration (FDA). The Arformoterol which is used for the treatment of Chronic obstructive pulmonary disease (COPD) are inhaled bronchodilator drugs which are delivered directly to the patient’s airways through a different mechanism. The formulated drug product is kept for stability study as per ICH guideline [1] and during its stability interval analysis by HPLC (High performance liquid chromatography), an unknown peak observed at level around 0.1% which is well below the identification threshold of 0.5% but after heating it crossed the identification threshold. The approach to identify anonymous species of Arformoterol aqueous formulation was adopted as first to generate the impurity in sample, isolate, enrich and Characterize through LC-MS/MS and NMR Spectroscopy. Based on the spectral data the anonymous species was identified as an “Imine impurity”, it is secondary degradant of Amine impurity of Arformoterol formed due to reaction with leachable observed in LDPE respules.展开更多
文摘The present method gives a detailed description for the development and validation of a simple stability indicating reverse phase liquid chromatographic method for 10-hydroxycamptothecin(10-HCTN) in the presence of its impurities namely Imp A and Imp B along with degradation products generated from forced degradation studies. The drug was subjected to stress conditions of hydrolysis (acid, base and neutral), oxidative, photolytic and thermal stress degradation. Degradation was observed when subjected to treatment with peroxides or under conditions normally used for typical acid and base hydrolysis. The drug was found to be stable under other stress conditions attempted such as photolytic and thermal. Successful separation and isolation of the drug from related impurities and degradation products formed under stress conditions was achieved on an Inertsil ODS-3V (250 mm × 4.6 mm, 5 μm) column using a phosphate buffer, acetonitrile, methanol and Nanopure water. The developed HPLC method was validated with respect to specificity, linearity, accuracy, precision, sensitivity, robustness and solution stability. The assay method was found to be linear in the range of 0.16 mg/mL to 0.24 mg/mL with a correlation coefficient of 0.999 and the linearity of the impurities was established from 0.02% (LOQ) to 0.3%. Recoveries of assay and impurities were found between 99.4% and 100.3%. The developed HPLC method can be used to determine the related substances and assay determinations of 10-HCTN and also to evaluate the quality and long term stability of production samples.
文摘The present method provides the detailed description of development and validation of a simple stability indicating re- verse phase column liquid chromatographic method for Olmesartan in the presence of its impurities namely Imp-A, Imp-B, Imp-C, Imp-D, Imp-E, Imp-F and Imp-G and degradation products generated from forced degradation studies. The drug substance was subjected to stress conditions of aqueous hydrolysis, Oxidative, photolytic and thermal stress degradation. The degradation of Olmesartan was observed under acid hydrolysis, base hydrolysis and peroxide. The drug was found to be stable to other stress conditions attempted. Successful separation of the drug from synthetic impu- rities and degradation products formed under stress conditions was achieved on symmetry C18, 150 mm × 4.6 mm, 5μ column using a phosphate buffer, Acetonitrile and Milli Q water. The developed LC method was validated with respect to specificity, linearity, accuracy, precision, raggedness and robustness. The assay method was found to be linear in the range of 250 μg?mL–1 to with 1000 μg?mL–1 correlation coefficient of 0.9999 and the linearity of the impurities was es- tablished from LOQ to 0.4%. Recoveries of assay and impurities were found between 98.5% and 101.2%. The devel- oped LC method to determine the related substances and assay determinations of Olmesartan can be used to evaluate the quality of regular production samples and stability samples. To best of our knowledge, the validated stability indi- cating LC method which separates all the impurities disclosed in this investigation was not published elsewhere.
文摘Budesonide is a corticosteroid used for the treatment of asthma via various matrices and inhalation mechanisms. An unknown peak of Budesonide aqueous formulation has been investigated during stability study wherein the impurity level observed around 0.1% well below the threshold 0.5%. The approach to identify anonymous species was adopted as first to generate the impurity in sample, isolate, enrich and was subjected to LC-MS/MS and NMR for spectral studies. Based on the spectral data the anonymous species were identified as a “Lumibudesonide’’ ((5aR,5bS,5cS,6S,7aS,7bS,10aR,11aS,11bS)-6-hydroxy-7b-(2-hydroxyacetyl)-5b,7a-dimethyl-9-propyl 1,5a,5b,5c,6,7,7a,7b,10a,11,11a,11b dodecahydrocyclopenta[2'',3'']cyclopropa [1'',2'':3', 4']benzo [1',2':4,5]indeno [1,2-d][1,3]dioxol-5(2H)-one), which is observed in photolysis of Budesonide.
文摘Arformoterol (R, R) is an enantiomer of racemic formoterol, was the first long-acting beta agonist (LABA), approved by U.S. food and Drug Administration (FDA). The Arformoterol which is used for the treatment of Chronic obstructive pulmonary disease (COPD) are inhaled bronchodilator drugs which are delivered directly to the patient’s airways through a different mechanism. The formulated drug product is kept for stability study as per ICH guideline [1] and during its stability interval analysis by HPLC (High performance liquid chromatography), an unknown peak observed at level around 0.1% which is well below the identification threshold of 0.5% but after heating it crossed the identification threshold. The approach to identify anonymous species of Arformoterol aqueous formulation was adopted as first to generate the impurity in sample, isolate, enrich and Characterize through LC-MS/MS and NMR Spectroscopy. Based on the spectral data the anonymous species was identified as an “Imine impurity”, it is secondary degradant of Amine impurity of Arformoterol formed due to reaction with leachable observed in LDPE respules.
