Pharmacokinetics and brain distribution of the therapeutic peptide liraglutide by a novel LC–MS/MS analysis

作者：Hyeon Seok Oh, Minkyu Choi, Tae Suk Lee, Yejin An, Eun Ji Park, Tae Hwan Kim, Soyoung Shin, Beom Soo Shin · 发表于：Journal of Analytical Science & Technology · 年份：2023 · DOI：10.1186/s40543-023-00382-5 · 被引用次数：16 · 研究领域：Diabetes Treatment and Management、Pancreatic function and diabetes、Metabolism, Diabetes, and Cancer

Abstract Liraglutide is a glucagon-like peptide-1 (GLP-1) analog that has been utilized for the treatment of type 2 diabetes mellitus. Liraglutide at a higher dose also shows beneficial effects in weight loss, which prompted its widespread use as an anti-obesity drug. The potential of liraglutide to treat Alzheimer’s disease and cognitive impairment has also been suggested. Nevertheless, the pharmacokinetics of liraglutide, including its distribution to the brain, has not been fully characterized. Therefore, this study aimed to develop a simple and sensitive bioanalytical method using liquid chromatography–tandem mass spectrometry (LC–MS/MS) and determine the pharmacokinetics and brain distribution of liraglutide in rats. Liraglutide in the rat plasma and brain tissue homogenates was extracted by protein precipitation using methanol. A gradient elution profile was used for chromatographic separation with mobile phases comprising 0.3% formic acid in water and 0.3% formic acid in acetonitrile. The mass spectrometry was operated in the positive electrospray ionization with multiple reaction monitoring mode. The lower limit of quantification of the present LC–MS/MS was 1 ng/mL in the plasma and 2 ng/mL in the brain tissue. Following intravenous injection (0.05 mg/kg, n = 5), plasma concentrations of liraglutide decreased monoexponentially with an average half-life of 3.67 h. The estimated absolute bioavailability of liraglutide after subcutaneous injection was 13.16%. Brain distr...