title: Novel MS solutions inspired by MIST.
abstract: To improve patient safety and to help avoid costly late-stage failures, the pharmaceutical industry, along with the US FDA and International Committee on Harmonization (ICH), recommends the identification of differences in drug metabolism between animals used in nonclinical safety assessments and humans as early as possible during the drug-development process. LC-MS is the technique of choice for detection and characterization of metabolites, however, the widely different LC-MS response observed for a new chemical entity (NCE) and its structurally related metabolites limits the direct use of LC-MS responses for quantitative determination of NCEs and metabolites. While no method provides completely accurate universal response, UV, corona charged aerosol detection (CAD), radioactivity, NMR and low-flow (< 20 µl/min) nanospray approaches provide opportunities to quantify metabolites in the absence of reference standards or radiolabeled material with enough precision to meet the needs of early clinical development.
authors.affiliation: Department of Biotransformation, Pharmaceutical Candidate Optimization, Bristol-Myers Squibb Company, Princeton, NJ, 08540, USA. ragu.ramanathan@bms.com
authors.forename: Ragu
authors.initials: R
authors.lastname: Ramanathan
authors.forename: Jonathan L
authors.initials: JL
authors.lastname: Josephs
authors.forename: Mohammed
authors.initials: M
authors.lastname: Jemal
authors.forename: Mark
authors.initials: M
authors.lastname: Arnold
authors.forename: W Griffith
authors.initials: WG
authors.lastname: Humphreys
mesh_terms: D000818:Animals; D002853:Chromatography, Liquid; D004781:Environmental Exposure / Q000032:analysis; D006801:Humans; D013058:Mass Spectrometry / Q000379:methods*; D004364:Pharmaceutical Preparations / Q000032:analysis* / Q000378:metabolism*; D015203:Reproducibility of Results
chemical_list: D004364:Pharmaceutical Preparations