Abstract
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.
Highlights
10-Hydroxycamptothecin((4S)-4-Ethyl-4,9-dihydroxy-1 H-pyrano[3’,4’:6,7]indolizino[1,2-b]quinoline-3,14(4H,1 2H)-dione) (10-HCTN) (Figure 1) is a potent DNA topoisomerase I inhibitor
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 Impurity A (Imp A) and Impurity B (Imp B) along with degradation products generated from forced degradation studies
The presence of residual impurities referred as related substances that are obtained in trace amounts during the synthesis of 10-HCTN, can have a significant impact on the quality and safety of the final drug
Summary
10-Hydroxycamptothecin((4S)-4-Ethyl-4,9-dihydroxy-1 H-pyrano[3’,4’:6,7]indolizino[1,2-b]quinoline-3,14(4H,1 2H)-dione) (10-HCTN) (Figure 1) is a potent DNA topoisomerase I inhibitor It induces apoptosis in human breast cancer cells. In order to optimize a process that provides the required Active Pharmaceutical Ingredient (API) with minimal amounts of impurities, it is important that these substances are identified by suitable and reliable analytic methods Such studies provide a deeper insight into the impurity profile of the API and allow researchers to identify synthetic or purification methods to lower and control their formation during the manufacturing of the drug product. A literature survey revealed that there is no HPLC method for performing a stability analysis that allows for the determination of related substances along with the quantitative estimation of 10-HCTN. High purity water was prepared by using a Nanopure diamond water purification system (Barnstead, Thermo Fisher Scientific, Mumbai, India)
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