Determination of xanomeline in human plasma by ionspray 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 ionspray 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 × 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 μl min⁻¹. The mobile phase eluant was introduced directly into the ionspray 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 xanomleine per milliliter of plasma. Sample run times were 2.5 min from one injection to the next.