Discerning the stability behaviour of mavacamten availing liquid chromatography ‐mass spectrometry and nuclear magnetic resonance spectroscopy: In silico toxicity and mutagenicity prediction of degradation products

AbstractThe present study aimed to separate, identify, and characterise the degradation products formed when mavacamten is exposed to stress degradation as well as the stability of the drug in various environments and also to understand its degradation chemistry. Prediction ofin silico toxicity and mutagenicity was aimed at the observed degradation products. Stress degradation along with stability studies and degradation kinetics were performed on mavacamten, and separation of degradation products was carried out by high-performance liquid chromatography. Tandem mass spectrometry studies were executed to characterise the structures of degradation products using product ion fragments. Orthogonally, nuclear magnetic resonance experiments were conducted to elucidate the structures having ambiguity in characterising them. Deductive Estimation of Risk from Existing Knowledge and Structure Activity Relationship Analysis using Hypotheses software were used to establishin silico toxicity and mutagenic profiles of mavacamten and its degradation products. Two degradation products of mavacamten found in acidic hydrolytic stress conditions were separated, identified, characterised, and proposed as 1-isopropylpyrimidine-2,4,6(1H,3H,5H)-trione and 1-phenylethanamine. Mavacamten was found to be stable under different pH and gastrointestinal conditions. The degradation kinetics of mavacamten under 1  N acidic condition followed zero-order kinetics, and it was degraded completely within 6...
Source: Journal of Mass Spectrometry - Category: Chemistry Authors: Tags: RESEARCH ARTICLE Source Type: research