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一种简单灵敏的 LC-MS/MS 法测定大鼠血浆中的龙胆酸及其药代动力学分析。

A simple and sensitive LC-MS/MS method for the determination of loganic acid in rat plasma and its pharmacokinetic analysis.

机构信息

School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, China.

School of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China.

出版信息

Biomed Chromatogr. 2024 Sep;38(9):e5951. doi: 10.1002/bmc.5951. Epub 2024 Jul 2.

DOI:10.1002/bmc.5951
PMID:38956830
Abstract

Loganic acid is an iridoid compound extracted from Gentianaceae plant Gentiana macrophylla Pall. It can effectively inhibit inflammation and tumor migration and has antioxidant activity. In this paper, we establish a simple, fast, sensitive and validated LC-MS method with the purpose of quantification of loganic acid in rat plasma with gliclazide as an internal standard (IS). Methanol was used to precipitate the protein in the plasma sample, and a C column (2.1 × 50 mm, 1.7 μm) was used for the separation of the target compound. Meanwhile, 0.1% formic acid water-methanol was employed as the mobile phase. Multiple reaction monitoring detection mode was adopted in detection with m/z 375.1 > 213.2 for loganic acid and m/z 322.1 > 169.9 for the IS, respectively, in negative ion scan mode. The linear range of calibration curve was 5.77-11,540.00 ng/ml, and the lower limit of detedtion was 2.89 ng/ml. The inter-day and intra-day precision and accuracy were <15% for lower limit of quantitation, low, middle and high quality control samples. This method was successfully used for the pharmacokinetic study of loganic acid in rat plasma at a dose range of 50-150 mg/kg for oral administration and 2 mg/kg for intravenous administration. The pharmacokinetic results showed that the oral bioavailability of loganic acid was low (2.71-5.58%).

摘要

(loganic acid) 丹酚酸是从龙胆科植物獐牙菜属植物獐牙菜中提取的环烯醚萜类化合物。它可以有效抑制炎症和肿瘤迁移,具有抗氧化活性。在本文中,我们建立了一种简单、快速、灵敏和验证的 LC-MS 方法,目的是定量测定大鼠血浆中的(loganic acid),以格列齐特为内标 (IS)。甲醇用于沉淀血浆样品中的蛋白质,并用 C 柱 (2.1 × 50mm,1.7μm) 分离目标化合物。同时,采用 0.1%甲酸-水-甲醇作为流动相。采用多反应监测检测模式,以负离子扫描模式分别检测 m/z 375.1 > 213.2 为(loganic acid)和 m/z 322.1 > 169.9 为 IS。校准曲线的线性范围为 5.77-11,540.00ng/ml,检测下限为 2.89ng/ml。低、中、高浓度质控样品的日内和日间精密度和准确度均<15%。该方法成功用于大鼠口服 50-150mg/kg 和静脉注射 2mg/kg 剂量范围内(loganic acid)的药代动力学研究。药代动力学结果表明(loganic acid)的口服生物利用度较低 (2.71-5.58%)。

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