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建立并验证了一种 LC-MS/MS 方法,用于定量检测大鼠血浆中的(+)-龙脑:应用于药代动力学研究。

Development and validation an LC-MS/MS method to quantify (+)-borneol in rat plasma: Application to a pharmacokinetic study.

机构信息

Jiangsu Simovay Pharmaceutical Co., Ltd., No.699-18, Xuanwu Avenue, Nanjing, Jiangsu 210042, China; State Key Laboratory of Translational Medicine and Innovative Drug, No.699-18, Xuanwu Avenue, Nanjing, Jiangsu 210042, China.

3D BioOptima Co., Ltd., 1338 Wuzhong Blvd., Suzhou, Jiangsu 215104, China.

出版信息

J Chromatogr B Analyt Technol Biomed Life Sci. 2019 Mar 1;1109:121-127. doi: 10.1016/j.jchromb.2019.01.023. Epub 2019 Jan 31.

Abstract

(+)-Borneol, a bicyclic monoterpene, has been shown to possess valuable biological properties and potential as a pharmaceutical agent due to anti-inflammatory, anti-oxidant and GABA receptor-enhancing functions; it also enhances the permeability of the blood brain barrier to improve the efficacy of CNS drugs. In this study, we have developed a simple, selective, and rapid liquid chromatography-tandem mass spectrometry method for the assay of (+)-borneol in rat plasma. Verapamil was used as an internal standard. Plasma samples were deproteinized using methanol. The analyte was detected by a mass spectrometer with positive atmospheric pressure chemical ionization by multiple reaction monitoring mode for transitions at m/z [M + H] 137.2 → 81.0 for (+)-borneol and 455.2 → 165.1 for verapamil. The method has been fully validated to ensure good selectivity, a satisfactory lower limit of quantification at 10.0 ng/mL, acceptable intra- and inter-day accuracy, and high precision. The method was used for the pharmacokinetic evaluation of (+)-borneol in Sprague-Dawley rats after intravenous, oral, and sublingual administration. The results indicate that oral bioavailability of (+)-borneol was extremely low but sublingual administration yielded rapid absorption and favorable bioavailability of (+)-borneol.

摘要

(+)- 龙脑,一种双环单萜,由于具有抗炎、抗氧化和 GABA 受体增强功能,被证明具有有价值的生物特性和作为药物制剂的潜力;它还可以增强血脑屏障对 CNS 药物的通透性,从而提高其疗效。在这项研究中,我们开发了一种简单、选择性强且快速的液相色谱-串联质谱法,用于测定大鼠血浆中的 (+)- 龙脑。维拉帕米被用作内标。用甲醇对血浆样品进行蛋白沉淀处理。采用正大气压化学电离多反应监测模式,通过质荷比 [M+H]+137.2→81.0 对 (+)- 龙脑和 455.2→165.1 对维拉帕米进行检测,对分析物进行检测。该方法已得到充分验证,以确保良好的选择性、10.0ng/mL 的满意定量下限、可接受的日内和日间准确度以及高精度。该方法用于评估静脉、口服和舌下给予 (+)- 龙脑后 Sprague-Dawley 大鼠的 (+)- 龙脑的药代动力学。结果表明,(+)- 龙脑的口服生物利用度极低,但舌下给药可迅速吸收,具有良好的 (+)- 龙脑生物利用度。

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