King-Ahmad Amanda J, Kalgutkar Amit S, Niosi Mark, Eng Heather, Holliman Christopher
Medicine Design, Worldwide Research & Development, Pfizer, Inc., Eastern Point Road, Groton, CT 06340, USA.
Medicine Design, Worldwide Research & Development, Pfizer, Inc., 1 Portland St, Cambridge, MA 02139, USA.
Bioanalysis. 2018 Mar 1;10(5):357-368. doi: 10.4155/bio-2017-0239. Epub 2018 Mar 8.
An LC-MS/MS assay for the quantitation of liraglutide, a peptide-based injectable glucagon-like peptide-1 receptor agonist, has been developed as a convenient alternative to the enzyme-linked immunosorbent assay, and used to characterize liraglutide pharmacokinetics in cynomolgus monkeys.
Assay calibration curves exhibited a linear dynamic range of 10-5000 ng/ml and correlation coefficient ≥0.98. Following a 30 μg/kg intravenous dose, liraglutide demonstrated low plasma clearance and distribution volume, which led to a terminal half-life of 6.59 h in monkeys.
The dynamic range of our LC-MS/MS assay provides sufficient coverage of the average efficacious liraglutide concentrations in human plasma, and can be used for pharmacokinetics/pharmacodynamics studies in animals and potentially in humans.
已开发出一种用于定量利拉鲁肽（一种基于肽的注射用胰高血糖素样肽-1受体激动剂）的液相色谱-串联质谱（LC-MS/MS）检测方法，作为酶联免疫吸附测定的便捷替代方法，并用于表征食蟹猴体内利拉鲁肽的药代动力学。
检测校准曲线的线性动态范围为10 - 5000 ng/ml，相关系数≥0.98。静脉注射剂量为30 μg/kg后，利拉鲁肽在血浆中的清除率和分布容积较低，导致猴子的终末半衰期为6.59小时。
我们的LC-MS/MS检测方法的动态范围足以覆盖人血浆中利拉鲁肽的平均有效浓度，可用于动物和潜在人体的药代动力学/药效学研究。
