Determination of xanomeline in human plasma by ion-spray tandem mass spectrometry.
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.
Murphy
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Lilly Research Laboratories, Lilly Corporate Center, Indianapolis, IN 46285.
Bonate
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Kasper
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Gillespie
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DeLong
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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
C090818:LY 282122; D018721:Muscarinic Agonists; D010277:Parasympathomimetics; D011725:Pyridines; D011743:Pyrimidines; D013830:Thiadiazoles; C075257:xanomeline