Determination of xanomeline (LY246708 tartrate), an investigational agent for the treatment of Alzheimer's disease, in rat and monkey plasma by capillary gas chromatography with nitrogen-phosphorus detection.
A GC method is described for the determination of xanomeline (LY246708 tartrate) and selected metabolites in rat and monkey plasma. The analytes, including an internal standard, were extracted from plasma at basic pH with hexane. The organic extract was evaporated to dryness and the residue was reconstituted in hexane. The analytes were separated from metabolites and endogenous substances using a DB1701 capillary column. The analytes were detected using nitrogen-phosphorus detection (NPD). The limit of quantitation was determined to be 8 ng/ml, and the response was linear from 8 to 800 ng/ml. The method has been successfully applied to rat and monkey samples pursuant to the development of xanomeline as an agent for the symptomatic treatment of Alzheimer's disease.
Brown
T J
TJ
Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN 46285, USA.
Shipley
L A
LA
D000544:Alzheimer Disease / Q000188:drug therapy*; D000818:Animals; D002197:Capillary Action; D002849:Chromatography, Gas / Q000379:methods* / Q000706:statistics & numerical data; D004285:Dogs; D000882:Haplorhini; D006586:Hexanes; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008862:Microsomes, Liver / Q000378:metabolism; D009584:Nitrogen; D010277:Parasympathomimetics; D010758:Phosphorus; D011725:Pyridines / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics; D051381:Rats; D012680:Sensitivity and Specificity; D013830:Thiadiazoles / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics
D006586:Hexanes; D010277:Parasympathomimetics; D011725:Pyridines; D013830:Thiadiazoles; D010758:Phosphorus; C075257:xanomeline; D009584:Nitrogen