title: Identification of a process impurity formed during synthesis of a nevirapine analogue HIV NNRT inhibitor using LC/MS and forced degradation studies.
abstract: Impurities in pharmaceutical products do not enhance the desired therapeutic effect and may, of course, have adverse effects. Impurities must therefore be limited or controlled for quality and safety considerations. Structural identification of an impurity is the first step in understanding the chemistry of its formation and subsequently controlling the impurity. In this article, the chemical structure of an unknown by-product formed during the synthesis of a nevirapine analogue HIV NNRT inhibitor was identified using a combination of low resolution, high resolution and H/D exchange LC/MS and LC/MS/MS. The origin of the impurity was investigated through a series of photo- and oxidative stress studies. It was concluded that this impurity is formed via a side-reaction of the last intermediate with the oxidant used in the synthesis.
authors.affiliation: Department of Analytical Sciences, Boehringer Ingelheim Pharmaceuticals Inc., 900 Ridgebury Road, Ridgefield, CT 06877, USA. fenghe.qiu@boehringer-ingelheim.com
authors.forename: Fenghe
authors.initials: F
authors.lastname: Qiu
authors.forename: Scott
authors.initials: S
authors.lastname: Pennino
authors.forename: Carl A
authors.initials: CA
authors.lastname: Busacca
authors.forename: Daniel L
authors.initials: DL
authors.lastname: Norwood
mesh_terms: D002851:Chromatography, High Pressure Liquid; D004340:Drug Contamination; D008027:Light; D013058:Mass Spectrometry; D019829:Nevirapine / Q000031:analogs & derivatives* / Q000032:analysis* / Q000138:chemical synthesis; D016877:Oxidants / Q000737:chemistry; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D010777:Photochemistry; D018894:Reverse Transcriptase Inhibitors / Q000032:analysis* / Q000138:chemical synthesis; D012996:Solutions; D012997:Solvents
chemical_list: D016877:Oxidants; D018894:Reverse Transcriptase Inhibitors; D012996:Solutions; D012997:Solvents; D019829:Nevirapine