title: Peptide bond-forming reagents HOAt and HATU are not mutagenic in the bacterial reverse mutation test.
abstract: The peptide bond-forming reagents 1-hydroxy-7-azabenzotriazole (HOAt, CAS 39968-33-7) and O-(7-Azabenzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate (HATU, CAS 148893-10-1) either have structural alerts, unclassified features or are considered out of domain when evaluated for potential mutagenicity with in silico programs DEREK and CaseUltra. Since they are commonly used reagents in pharmaceutical drug syntheses, they may become drug substance or drug product impurities and would need to be either controlled to appropriately safe levels or tested for mutagenicity. Both reagents were tested in the bacterial reverse mutation (Ames) test at Covance, under GLP conditions, following the OECD test guideline and ICH S2(R1) recommendations and found to be negative. Our data show that HOAt and HATU-common pharmaceutical synthesis reagents-are not mutagenic, and can be treated as ordinary drug impurities.
authors: AbbVie, Inc., 1 North Chicago Road, North Chicago, Illinois.
authors: John
authors: J
authors: Nicolette
authors: Covance Laboratories Inc., 671 S. Meridian Rd, Greenfield, Indiana.
authors: Robin E
authors: RE
authors: Neft
authors: Covance Laboratories Inc., 671 S. Meridian Rd, Greenfield, Indiana.
authors: Jessica
authors: J
authors: Vanosdol
authors: AbbVie, Inc., 1 North Chicago Road, North Chicago, Illinois.
authors: Joel
authors: J
authors: Murray
mesh_terms: D000818:Animals; D001372:Aza Compounds / Q000737:chemistry* / Q000633:toxicity*; D007202:Indicators and Reagents / Q000737:chemistry / Q000633:toxicity; D008297:Male; D009152:Mutagenicity Tests; D009153:Mutagens / Q000737:chemistry / Q000633:toxicity; D011725:Pyridines / Q000737:chemistry* / Q000633:toxicity*; D017207:Rats, Sprague-Dawley; D012486:Salmonella typhimurium / Q000187:drug effects / Q000235:genetics; D014230:Triazoles / Q000737:chemistry* / Q000633:toxicity*
chemical_list: D001372:Aza Compounds; D007202:Indicators and Reagents; D009153:Mutagens; D011725:Pyridines; D014230:Triazoles; C472082:N-((1H-1,2,3-triazolo-(4,5-b)pyridin-1-yloxy)(dimethylamino)methylene)N-methylmethanaminium hexafluorophosphate; C435757:1-hydroxy-7-azabenzotriazole
keywords: Ames assay; ICH M7; impurities