title: From definition to implementation: a cross-industry perspective of past, current and future MIST strategies.
abstract: The article describes and discusses the evolution of strategies to characterize metabolites in support of safety studies over the last 40 years, as well as future trends. Approaches to derive qualitative and quantitative information on metabolites are described, with a particular focus on the comparison of options to quantify metabolites in the absence of authentic standards. Current strategies to assess metabolite profiles are summarized into four general approaches and compared against a number of key criteria. Potential future strategies are discussed, including the use of clinical samples as the starting point for metabolite investigations, minimizing the need for animal radiolabelled studies and establishing metabolite safety without radiolabelled studies in animals or human.
authors: Pharmacokinetics, Dynamics and Metabolism, Pfizer Global Research and Development, Sandwich, Kent, UK. angus.nedderman@pfizer.com
authors: Angus N R
authors: AN
authors: Nedderman
authors: Gordon J
authors: GJ
authors: Dear
authors: Stephanie
authors: S
authors: North
authors: R Scott
authors: RS
authors: Obach
authors: David
authors: D
authors: Higton
mesh_terms: D000818:Animals; D004345:Drug Industry / Q000639:trends*; D006801:Humans; D013058:Mass Spectrometry; D009570:Nitriles / Q000737:chemistry / Q000378:metabolism; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D011720:Pyrazoles / Q000737:chemistry / Q000378:metabolism
chemical_list: D009570:Nitriles; D004364:Pharmaceutical Preparations; D011720:Pyrazoles; C531151:UK 453,061