Abstract
Degradation pathway for gefitinib is established as per ICH recommendations by validated and stability in-dicating reverse phase liquid chromatographic method. Gefitinib is subjected to stress conditions of acid, base, oxidation, thermal and photolysis. Significant degradation is observed in acid and base stress condi-tions. Two impurities are studied among which one impurity is found prominent degradant. The stress sam-ples are assayed against a qualified reference standard and the mass balance is found close to 99.5%. Effi-cient chromatographic separation is achieved on a Agilent make XDB-C18, 50 × 4.6 mm with 1.8 µm parti-cles stationary phase with simple mobile phase combination delivered in gradient mode and quantification is carried at 250 nm at a flow rate of 0.5 mL?min-1. In the developed RPLC method the resolution between ge-fitinib and the potential impurities is found to be greater than 5.0. Regression analysis shows an r value (cor-relation coefficient) of greater than 0.998 for gefitinib and the two potential impurities. This method is capa-ble to detect the impurities of gefitinib at a level of 0.01% with respect to test concentration of 0.5 mg?mL-1 for a 4-µL injection volume. The developed RRLC method is validated with respect to specificity, linearity & range, accuracy, precision and robustness for impurities determination and assay determination.
Highlights
Gefitinib: N-(3-chloro-4-fluoro-phenyl)-7-methoxy-6-(3morpholin-4-yl propoxy) quinazolin-4-amine (Figure 1) is an anticancer
Literature survey reveals an analytical method is reported for the determination of gefitinib in human plasma, mouse plasma and tissues using high performance liquid chromatography coupled to tandem mass spectrometry and a method is reported for estimation of gefitinib in tablet dosage forms by RP-HPLC [5,6]
In this paper we describe validation of related substances and assay method for accurate quantification of two potential process impurities in gefitinib samples as per international conference on harmonization (ICH) recommendations
Summary
Gefitinib: N-(3-chloro-4-fluoro-phenyl)-7-methoxy-6-(3morpholin-4-yl propoxy) quinazolin-4-amine (Figure 1) is an anticancer. The generic name of gefitinib is iressa; gefitinib is a drug that is used to treat several types of cancer. It works by preventing lung cancer cells from growing and multiplying. As far as we are aware there is no stability-indicating rapid resolution liquid chromatography method for determination of related substances and assay determination of gefitinib. In this paper we describe validation of related substances and assay method for accurate quantification of two potential process impurities in gefitinib samples as per ICH recommendations. Intensive stress studies are carried out on gefitinib; a stability-indicating method is developed, which could separate various degradants. HPLC grade ammonium acetate and acetonitrile are purchased from Merck, Darmstadt, Germany. All samples and impurities used in this study are of having greater than 99.8% purity
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