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超高效液相色谱-串联质谱法测定小鼠血浆中乙酰紫堇灵及其药代动力学研究

Determination and Pharmacokinetics of Acetylcorynoline in Mouse Plasma by UPLC-MS/MS.

作者信息

Xu Mengzhi, Dong Xicheng, Fan Yishun, Wang Yucan, Xu Jinmiao, Ma Jianshe, Yu Xiaomin

机构信息

Department of Orthopedics, The First People's Hospital of Yuhang District, Hangzhou, China.

Functional Experiment Teaching Center, School of Basic Medical Sciences, Wenzhou Medical University, Wenzhou, China.

出版信息

Int J Anal Chem. 2025 Feb 6;2025:5319104. doi: 10.1155/ianc/5319104. eCollection 2025.

Abstract

Acetylcorynoline is an alkaloid isolated from the tubers of Cham. et Schltdl. It has anti-inflammatory properties with the potential to treat Parkinson's disease. However, the use of UPLC-MS/MS for identifying acetylcorynoline in mouse plasma has not yet been explored. The present study aimed to develop a fast and selective method for determining the amount of acetylcorynoline in mouse plasma using UPLC-MS/MS. Plasma samples (10 μL) were prepared using methanol-induced protein precipitation following the addition of aconitine as an internal standard. The chromatographic separation was accomplished using a UPLC HSS T3 column with acetonitrile and 0.1% formic acid as the mobile phase. The analytes were run for 4.0 min in total. The target fragment ions / 410.4 ⟶ 350.3 for acetylcorynoline and / 646.6 ⟶ 586.5 for internal standard were used for quantification using multiple reaction monitoring mode. The mouse blood was obtained at different time points after intravenous (5 mg/kg) and oral (20 mg/kg) administration of acetylcorynoline. The calibration plots for acetylcorynoline in mouse plasma showed a linear trend over the whole range of 1-2000 ng/mL. Both the intraday and interday precision relative standard deviations were less than 11%. The half-life in mice was found to be 2.6 ± 0.7 h and 2.7 ± 0.8 h following oral and intravenous administration, respectively. The bioavailability was determined to be 58.9%. The pharmacokinetics and bioavailability of acetylcorynoline in mice were effectively analyzed using this UPLC-MS/MS method, which had a runtime of 4 min per sample and required only 10 μL of plasma.

摘要

乙酰紫堇灵是从Cham. et Schltdl.的块茎中分离出的一种生物碱。它具有抗炎特性,有可能用于治疗帕金森病。然而,尚未探索使用超高效液相色谱-串联质谱法(UPLC-MS/MS)来鉴定小鼠血浆中的乙酰紫堇灵。本研究旨在开发一种快速且选择性的方法,使用UPLC-MS/MS测定小鼠血浆中乙酰紫堇灵的含量。在加入乌头碱作为内标后,采用甲醇诱导蛋白沉淀法制备血浆样品(10 μL)。使用UPLC HSS T3柱,以乙腈和0.1%甲酸作为流动相进行色谱分离。分析物总共运行4.0分钟。使用多反应监测模式,以乙酰紫堇灵的目标碎片离子/ 410.4 ⟶ 350.3和内标的目标碎片离子/ 646.6 ⟶ 586.5进行定量。在静脉注射(5 mg/kg)和口服(20 mg/kg)乙酰紫堇灵后的不同时间点采集小鼠血液。小鼠血浆中乙酰紫堇灵的校准曲线在1 - 2000 ng/mL的整个范围内呈线性趋势。日内和日间精密度相对标准偏差均小于11%。口服和静脉注射后,小鼠体内的半衰期分别为2.6 ± 0.7小时和2.7 ± 0.8小时。生物利用度测定为58.9%。使用这种UPLC-MS/MS方法有效地分析了乙酰紫堇灵在小鼠体内的药代动力学和生物利用度,该方法每个样品的运行时间为4分钟,仅需10 μL血浆。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9269/11825197/5677c3faa601/IJAC2025-5319104.001.jpg

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