Highly sensitive quantitative estimation of genotoxic impurities from API and drug formulation using LC/MS/MS

The toxicological assessment of Genotoxic Impurities (GTI) and the determination of acceptable limits for such impurities in Active Pharmaceutical Ingredients (API) is a difficult issue. As per European Medicines Agency (EMEA) guidance, a Threshold of Toxicological Concern (TTC) value of 1.5 μg/day intake of a genotoxic impurity is considered to be acceptable for most pharmaceuticals.
Dronedarone is a drug mainly used for indications of cardiac arrhythmias. GTI of this drug has been quantitated here. Method has been optimized for simultaneous analysis of DRN-IA {2-n-butyl-3-[4-(3-di-n-butylamino-propoxy)benzoyl]-5-nitro benzofuran}, DRN-IB {5-amino-3-[4-(3-di-n-butylamino-propoxy)benzoyl}-2-n-but yl benzofuran} and BHBNB {2-n-butyl-3-(4-hydroxy benzoyl)-5-nitro benzofuran}. Structures of Dronedarone and its GTI are shown in Figure 1.
As literature references available on GTI analysis are minimal, the feature of automatic MRM optimisation in LCMS-8040 makes method development process less tedious. In addition, the lowest dwell time and pause time and ultrafast polarity switching of LCMS-8040 ensures uncompromised and high sensitive quantitation.

Content Type:
Paper
Document Number:
PO-CON1467E
Product Type:
Liquid Chromatography, Liquid Chromatograph-Mass Spectrometry, Mass Spectrometry
Keywords:
genotoxic impurities, Pharmaceutical, Life Science, Development (Formulation, Scale-up, Method development), LCMS-8040, Nexera UHPLC, Shim-pack XR-ODS II
Language:
English
File Name:
ipo114052.pdf
File Size:
473kb

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