Impurities

ABSTRACTThe objective of the study was to develop and evaluate the reverse phase high performance liquid chromatography (RP-HPLC) method for the quantitative determination of potential impurities of Mirabegron active pharmaceutical ingredient. The method uses Puratis C18 column (250 × 4.6mm, 5µm ) with mobile phase A consisted, 20 mM Ammonium acetate, pH adjusted to 4.5 and mobile phase B consisted methanol  with a gradient programme. The column temperature was maintained at 25 °C and the detection was carried out at 247 nm. Efficient and reproducible chromatographic separation was achieved on C18 stationary phase in gradient elution profile. The newly developed HPLC method was validated according to ICH guidelines considering three impurities to demonstrate precision, linearity, accuracy and robustness of the method. The developed HPLC method was found to be accurate and sensitive. The correlation coefficient values are greater than 0.99 for Mirabegron and its three impurities. Detection limit and quantitation limit was 0.04ppm and 0.14ppm respectively, indicating the high sensitivity of the newly developed method. Accuracy of the method was established based on the recovery obtained between 99.67% and 104.98% for all impurities. The result of robustness study also indicates that the method is robust and is unaffected by small variation in chromatographic conditions. The proposed HPLC method provides reliable, reproducible, accurate and sensitive for the quantification of Mirabegron related substances. Keywords: Mirabegron; Impurities; RP-HPLC; Validation.

A simple, sensitive, selective and stability indicating UPLC method has been developed for the quantitative determination of potential impurities of allopurinol active pharmaceutical ingredient. Allopurinol, its five impurities and degradation products were separated efficiently by using the mobile phase consisted of sodium perchlorate (10 mM, pH 3.0)and acetonitrile on a HSS T3P stationary phase in gradient elution profile. Forced degradation study confirmed that the newly developed method was specific and selective to the degradation products. The newly developed UPLC method was validated according to ICH guidelines considering five impurities to demonstrate specificity, precision, linearity, accuracy and stability indicating nature of the method. Regression analysis showed correlation coefficient value greater than 0.99 for allopurinol and its five impurities. Detection limit of impurities was in the range of 0.002–0.006% indicating the high sensitivity of the newly developed method. Accuracy of the method was established based on the recovery obtained between 91.7% and 106.6% for all impurities.

As per ICH guideline impurity may be defined as any component of drug product that is not the drug substance or an excipient. Now a day apart from purity profile there are an increasing essentiality of impurity profile by regulatory agency. Different regulatory agencies like ICH,USFDA, TGA, etc. work on control and identification of impurities in pharmaceutical dosage forms. To identify and characterize impurities are essential for establishing the biological safety of an pharmaceutical dosage forms. The various pharmacopoeias like IP, BP, USP, etc. were allowed certain limits of impurities in pharmaceutical dosage forms. This review article mainly focuses on various methods available to identify and characterize impurities in pharmaceutical dosage forms. Among all, the most specific techniques are NMR, MASS, GC-MS, LC-MS, HPLC-DAD-MS, LC-MS-MS, HPLC-DAD-NMR-MASS, Capillary electrophoresis, Mass and Flash chromatography. Key words: Impurities, identification, HPLC-DAD-MS.