title: Identification, control strategies, and analytical approaches for the determination of potential genotoxic impurities in pharmaceuticals: a comprehensive review.
abstract: Potential genotoxic impurities in pharmaceuticals at trace levels are of increasing concern to both pharmaceutical industries and regulatory agencies due to their possibility for human carcinogenesis. Molecular functional groups that render starting materials and synthetic intermediates as reactive building blocks for small molecules may also be responsible for their genotoxicity. Determination of these genotoxic impurities at trace levels requires highly sensitive and selective analytical methodologies, which poses tremendous challenges on analytical communities in pharmaceutical research and development. Experimental guidance for the analytical determination of some important classes of genotoxic impurities is still unavailable in the literature. Therefore, the present review explores the structural alerts of commonly encountered potential genotoxic impurities, draft guidance of various regulatory authorities in order to control the level of impurities in drug substances and to assess their toxicity. This review also describes the analytical considerations for the determination of potential genotoxic impurities at trace levels and finally few case studies are also discussed for the determination of some important classes of potential genotoxic impurities. It is the authors' intention to provide a complete strategy that helps analytical scientists for the analysis of such potential genotoxic impurities in pharmaceuticals.
authors.affiliation: Department of Chemistry, Faculty of Science, Universiti Teknologi Malaysia, Johor, Malaysia.
authors.forename: Ambavaram Vijaya Bhaskar
authors.initials: AV
authors.lastname: Reddy
authors.forename: Jafariah
authors.initials: J
authors.lastname: Jaafar
authors.forename: Khalid
authors.initials: K
authors.lastname: Umar
authors.forename: Zaiton Abdul
authors.initials: ZA
authors.lastname: Majid
authors.forename: Azmi Bin
authors.initials: AB
authors.lastname: Aris
authors.forename: Juhaizah
authors.initials: J
authors.lastname: Talib
authors.forename: Gajulapalle
authors.initials: G
authors.lastname: Madhavi
mesh_terms: D004340:Drug Contamination / Q000517:prevention & control; D004345:Drug Industry; D006801:Humans; D009153:Mutagens / Q000032:analysis*; D004364:Pharmaceutical Preparations / Q000032:analysis*
chemical_list: D009153:Mutagens; D004364:Pharmaceutical Preparations
keywords: Alkyl halides; Control strategies; Regulatory guidance; Toxicology; Trace analysis