Murphy A T, Bonate P L, Kasper S C, Gillespie T A, DeLong A F
Lilly Research Laboratories, Lilly Corporate Center, Indianapolis, IN 46285.
Biol Mass Spectrom. 1994 Oct;23(10):621-5. doi: 10.1002/bms.1200231004.
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.
占诺美林是一种毒蕈碱受体激动剂，目前正处于治疗阿尔茨海默病的II期临床试验阶段。已开发出一种快速、灵敏且特异的测定方法，使用离子喷雾串联质谱法来测定占诺美林的血浆浓度。占诺美林和一种结构类似物LY282122从碱化血浆中萃取到己烷中。将干燥的己烷萃取物复溶后注入一根10×1毫米的C18反相柱。以33毫摩尔/升醋酸铵和0.33%醋酸的流动相，在30/70（v/v）水-乙腈体系中，以50微升/分钟的流速泵入柱中。流动相洗脱液直接引入离子喷雾接口。质谱仪以正离子模式运行，用于特异性检测占诺美林和内标的产物离子。该方法的线性范围为每毫升血浆中占诺美林0.075 - 5.0纳克。从一次进样到下一次进样，样品运行时间为2.5分钟。
