ULTRA HIGH PERFORMANCE LIQUID CHROMATOGRAPHIC DETERMINATION OF GENOTOXIC IMPURITIES IN FEBUXOSTAT DRUG SUBSTANCE AND PRODUCTS

Objective: An efficient ultra-high performance liquid chromatographic (UHPLC or Infinity LC 1290) method has been developed and validated for the quantification of possible carcinogenic or genotoxic impurities in febuxostat drug substances and drug products at 18 µg/ml level.Methods: This method includes the conclusion of four potential genotoxic impurities in febuxostat. The mobile phase is trifluoroacetic acid, acetonitrile, and water with linear gradient elution. The UHPLC column used for the analysis was zorbax RRHD eclipse plus C18 with a length of100 mm, internal diameter of 2.1 mm, and particle size of 1.8 µ.Results: The limit of detection and limit of quantitation of the impurities are <0.1 (0.00001%) and 0.3 µg/ml (0.00003%) with respect to febuxostat test concentration of 1000 µg/ml, respectively. This method has been validated as per ICH guidelines Q2 (R1).Conclusion: A rapid, cost-effective infinity LC method was wonderfully established for quantitative analysis of possible genotoxic impurities of febuxostat drug substance and drug products.Keywords: Febuxostat, Genotoxic impurities, Ultra-high performance liquid chromatograph, Infinity-LC 1290, Validatio

TRACE LEVEL DETERMINATION AND QUANTIFICATION OF POTENTIAL GENOTOXIC IMPURITIES IN DASATINIB DRUG SUBSTANCE BY UHPLC/INFINITY LC

Objective: A simple, cost-effective and mass compatible ultra-high fast performance liquid chromatographic (Agilent-Infinity LC 1290) method has been developed and validated for the determination of potentially genotoxic impurities in dasatinib active pharmaceutical ingredients.Methods: This method comprises the determination of three possible genotoxic impurities in dasatinib. The mobile phase is trifluoroacetic acid, acetonitrile and water with linear gradient elution curve number 6. The column used for the development and validation is zorbax RRHD eclipse plus C18 with the length of 50 mm, the internal diameter of 2.1 mm and particle size of 1.8 microns.Results: The limit of detection of the potential genotoxic impurities are less than 0.1 µg/ml with respect to dasatinib test concentration of 1000 µg/ml. The limit of quantification of the potential genotoxic impurities is less than 0.3 µg/ml with respect to dasatinib test concentration of 1000 µg/ml.Conclusion: This method has been validated as per ICH guidelines Q2 (R1). These three potential mutagenic impurities are not degradant impurities of dasatinib and its only process related impurities. The method development has been approached using the QbD principle

SENSITIVE DETERMINATION OF RELATED SUBSTANCES IN PIOGLITAZONE HYDROCHLORIDE BY HPLC

Objective: An efficient, high performance liquid chromatographic method has been developed and validated for the quantification of related substances in pioglitazone hydrochloride drug substance.Methods: This method includes the determination of three related substances in pioglitazone hydrochloride. The mobile phase A is 0.1% w/v triethylamine in water with pH 2.5 adjusted by dilute phosphoric acid. The mobile phase B is premixed and degassed mixtures of acetonitrile and methanol. The flow rate was 1 ml/min. The elution used was gradient mode. The HPLC column used for the analysis was symmetry C18 with a length of 250 mm, the internal diameter of 4.6 mm and particle size of 5.0 microns.Results: The developed method was found to be linear with the range of 0.006-250% with a coefficient of correlation 0.99. The precision study revealed that the percentage relative standard deviation was within the acceptable limit. The limit of detection and limit of quantitation of the impurities was less than 0.002%and 0.006% with respect to pioglitazone hydrochloride test concentration of 2000 µg/ml respectively. This method has been validated as per ICH guidelines Q2 (R1).Conclusion: A reliable, economical HPLC method was magnificently established for quantitative analysis of related substances of pioglitazone hydrochloride drug substance