Study of Degradation Products and Degradation Pathways of ECD and Its Drug Product, ECD Kit

Determination of Impurities in Pharmaceuticals: Why and How?

“…Steps for the determination of potential degradation products, including a science-based risk assessment, can been addressed as below [11,25]:…”

“…Before conducting method validation, all of the impurities shall be verified by spiked or known addition to demonstrate they do exist under the "real" storage conditions such as accelerated or long-term storage conditions. Otherwise, it may not be necessary to examine specifically for certain degradation products if they are not formed under the "real" storage conditions [11,25,39].…”

“…Potential genotoxic impurities can be determined according to the published literature, results of gene mutation in bacteria, in vitro and in vivo tests of chromosomal damage in mammalian cells or rodent hematopoietic cells, or/and comparative structural analysis to identify chemical functional moieties correlated with mutagenicity [16]. Moreover, daily exposure, duration of exposure on the effects of degradation products and genotoxic impurities, and theoretical clinical dose, whereas potential [20,23,[25][26][27].…”

“…In addition to the regulatory requirements, internal and external scientific and technical needs are the second perspective to conduct an impurity study. Impurity determination and forced degradation studies are two of the basic requirements as a tool to predict potential DPIs, to develop analytical method, synthetic processes, and formulation, to receive a better understanding of storage conditions, stability of drug product, and to obtain information of degradation products/pathways, as well as to evaluate the specificity (selectivity) of assay method [22][23][24][25].…”

“…This includes subjecting of API or drug products to stress studies of light, heat, humidity, acid and base hydrolysis, and oxidation to evaluate the HPLC separation resolution, mass balance, etc. [3,22,24,25].…”