Affiliation:
1. Department of Pharmaceutical Analysis, National Institute of Pharmaceutical Education and Research (NIPER) - Ahmedabad, Gujarat, India.
Abstract
Aim:
The current research aims to establish a stability-indicating analytical method (SIAM) for
the quantification of evodiamine (EVO), characterization of its degradation impurity, and establishment
of possible degradation pathways.
Background:
None of the degradation impurities of EVO is known and the mechanism of their formation
has not been reported in any literature to date. Moreover, a SIAM for EVO is not available in any public
domain.
Objective:
The objective of this study is to characterize the degradation impurity of EVO by LC-MS/MS,
proposing its molecular structure, identifying possible degradation pathways of generation of its impurity,
and establishing a SIAM.
Method:
To assist future product development, a degradation study of EVO was performed and an RPHPLC-
based SIAM was developed. The major degradation product was characterized by LC-Q-TOFMS/
MS. In addition, in silico toxicity prediction was performed using the ProTox-ІI toxicity predictor.
Result:
The method was found to be linear, accurate, precise, and robust over the range of 12.5 to 100 μg
/mL of EVO. The method met all the acceptance criteria as specified in the ICH guideline. Only one degradation
product (9% of the drug area) of EVO was generated in acidic hydrolytic conditions. The degradation
product was found to be potentially inactive for hepatotoxicity and immunotoxicity, with a confidence
score of more than 0.7 (70%). Moreover, the confidence score for carcinogenicity, mutagenicity,
and cytotoxicity was less than 0.7, indicating it was moderately inactive for these toxicities.
Conclusion:
The molecule was found to be stable in the majority of the tested stress conditions. However,
the degradation product generated in acidic hydrolytic stress was characterized using LC-Q-TOF-MS/MS,
which was unknown to date. The novelty of this research can be justified by the unavailability of any
SIAM of EVO and the absence of any report on its susceptibility to degradation in the presence of different
potential stressors. Moreover, the potential toxicity of the molecule and its impurity was not known
previously. The reported degradation impurity may be useful to set the quality control acceptance criteria
for EVO. Additionally, pharmaceutical industries and research laboratories may use the developed method
for the analysis of quality control and stability samples of EVO.
Publisher
Bentham Science Publishers Ltd.