title: Determination of xanomeline in human plasma by ion-spray tandem mass spectrometry.
abstract: Xanomeline is a muscarinic receptor agonist currently in phase II clinical trials for the treatment of Alzheimer's disease. A fast, sensitive and specific assay has been developed to determine xanomeline plasma concentrations using ion-spray tandem mass spectrometry. Xanomeline and a structural analog, LY282122, were extracted from basifed plasma into hexane. The dried hexane extracts were reconstituted and injected onto a 10 x 1 mm C18 reversed-phase column. A mobile phase of 33 mM ammonium acetate and 0.33% acetic acid in 30/70 (v/v) water-acetonitrile was pumped through the column at 50 microliters min-1. The mobile phase eluant was introduced directly into the ion-spray interface. The mass spectrometer was operated in the positive ion mode for specific detection of the product ions of xanomeline and the internal standard. The method has a linear range of 0.075-5.0 ng xanomeline per milliliter of plasma. Sample run times were 2.5 min from one injection to the next.
authors.affiliation: Lilly Research Laboratories, Lilly Corporate Center, Indianapolis, IN 46285.
authors.forename: A T
authors.initials: AT
authors.lastname: Murphy
authors.forename: P L
authors.initials: PL
authors.lastname: Bonate
authors.forename: S C
authors.initials: SC
authors.lastname: Kasper
authors.forename: T A
authors.initials: TA
authors.lastname: Gillespie
authors.forename: A F
authors.initials: AF
authors.lastname: DeLong
mesh_terms: D006801:Humans; D013058:Mass Spectrometry; D018721:Muscarinic Agonists / Q000097:blood* / Q000493:pharmacokinetics; D010277:Parasympathomimetics / Q000097:blood* / Q000493:pharmacokinetics; D011725:Pyridines / Q000097:blood* / Q000493:pharmacokinetics; D011743:Pyrimidines / Q000097:blood / Q000493:pharmacokinetics; D011786:Quality Control; D013830:Thiadiazoles / Q000097:blood* / Q000493:pharmacokinetics
chemical_list: C090818:LY 282122; D018721:Muscarinic Agonists; D010277:Parasympathomimetics; D011725:Pyridines; D011743:Pyrimidines; D013830:Thiadiazoles; C075257:xanomeline