Genotoxic Impurities and Its Risk Assessment in Drug Compounds

Abstract

The present work is based on a assess analysis of the literature in order to define the genotoxic impurities present in the drug substances and drug products. Starting from the definition of genotoxic impurities, sources of genotoxic impurities, their generation and classification based on their toxicity. The article also explains the various regulatory guidelines to control the genotoxic impurities in drug substances. Isolation, qualification of impurity and its identification along with quantification by the various analytical methods is also described in this review article.

Stability‐indicating method for quantification of potential genotoxic impurity and other organic impurities of chlorzoxazone using hyphenated techniques

“…Also as the product contains genotoxic impurity (2-amino-4-chlorophenol), it is essential to have a more sophisticated method/technique for the quantification of the same. Considering the sensitivity and toxicity of this impurity (its consumption of high levels will cause cancer), we have selected the RP-HPLC-MS/MS technique for the estimation of 2-amino-4-chlorophenol in ppm level (Figure 1) [19][20][21][22][23]. Both methods were developed and validated considering the International Council for Harmonization (ICH) requirements, which met its acceptance criteria and were found to be specific, linear, accurate, precise, and robust [24][25][26][27][28].…”

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“…1. Impurity-A and Impurity-B are confirmed as potential genotoxic impurities based on the available literature [1][2][3][4][5] . The trace level impurities of Impurity-A and Impurity-B present in the Bazedoxifene drug substance or drug product may cause severe harmful effects on human health.…”

“…The trace level impurities of Impurity-A and Impurity-B present in the Bazedoxifene drug substance or drug product may cause severe harmful effects on human health. The concentration limit of genotoxic impurities, Impurity-A, and Impurity-B was calculated based on TTC [1][2][3][4][5] and maximum daily dose [1][2][3][4][5][6][7][8] . Impurity-A and Impurity-B each must to be controlled at below 75ppm.…”