DETERMINATION OF XANOMELINE IN HUMAN PLASMA BY IONSPRAY TANDEM MASS-SPECTROMETRY

Xanomeline is a muscarinic receptor agonist currently in phase II clin ical trials for the treatment of Alzheimer's disease. A fast, sensitiv e and specific assay has been developed to determine xanomeline plasma concentrations using ionspray tandem mass spectrometry. Xanomeline an d a structural analog, LY282122, were extracted from basifed plasma in to hexane. The dried hexane extracts were reconstituted and injected o nto a 10 x 1 mm C-18 reversed-phase column. A mobile phase of 33 mM am monium acetate and 0.33% acetic acid in 30/70 (v/v) water-acetonitrile was pumped through the column at 50 mu l min(-1). The mobile phase el uant was introduced directly into the ionspray interface. The mass spe ctrometer was operated in the positive ion mode for specific detection of the product ions of xanomeline and the internal standard. The meth od has a linear range of 0.075-5.0 ng xanomleine per milliliter of pla sma. Sample run times were 2.5 min from one injection to the next.