Determination of monocrotaline and usaramine in rat plasma by UPLC-MS/MS and their pharmacokinetics

IF 16.4 1区化学 Q1 CHEMISTRY, MULTIDISCIPLINARY

Accounts of Chemical Research Pub Date : 2023-11-14 DOI:10.1556/1326.2023.01160

Fan Chen, Ziyue Wang, Xiaoyun Xia, Wanhang Wang, Yizhe Ma, Xiuwei Shen, Xuzhao Zhou, Congcong Wen

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Abstract

Abstract An ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was developed for the determination of monocrotaline and usaramine in rat plasma, to study the plasma drug concentration and pharmacokinetics, and to calculate the absolute bioavailability. The plasma was treated with acetonitrile and methanol (9:1, v/v) protein precipitation method. The chromatographic column was UPLC HSS T3 (50 mm × 2.1 mm, 1.7 μm), the mobile phase was methanol-water (containing 0.1% formic acid with 10 mM ammonium acetate in water), and the elution time was 4 min at a flow rate of 0.4 mL min −1 . Electrospray ionization (ESI) positive ion mode was used for detection and multiple reaction monitoring (MRM) mode was used for quantitative analysis. Monocrotaline and usaramine were administered sublingual intravenously (iv) 1 mg kg −1 and orally (po) 5 mg kg −1 , respectively, with 6 rats in each group, for a total of 24 rats. Then the pharmacokinetic differences in rats were evaluated. For the UPLC-MS/MS method, the calibration curve showed good linearity in the range of 2–2,000 ng mL −1 , where r was greater than 0.99. The precision, accuracy, recovery, matrix effect and stability results were all consistent with the requirements of biological sample detection methods. to provide scientific experimental basis for the basic research The bioavailability of monocrotaline and usaramine in rat plasma was calculated, which was 43.5 and 19.5%, respectively.

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超高效液相色谱-质谱联用法测定大鼠血浆中苦参碱和乌苏胺的含量及其药动学

摘要建立了超高效液相色谱-串联质谱法(UPLC-MS/MS)测定大鼠血浆中苦参碱和乌萨拉明的方法，研究其血药浓度和药代动力学，并计算绝对生物利用度。血浆用乙腈-甲醇(9:1,v/v)蛋白沉淀法处理。色谱柱为UPLC HSS T3 (50 mm × 2.1 mm, 1.7 μm)，流动相为甲醇-水(含0.1%甲酸和10 mm乙酸铵)，洗脱时间为4 min，流速为0.4 mL min−1。采用电喷雾电离(ESI)正离子模式进行检测，多反应监测(MRM)模式进行定量分析。分别舌下静脉注射(iv) 1 mg kg - 1和口服(po) 5 mg kg - 1，每组6只大鼠，共24只大鼠。然后评价其在大鼠体内的药动学差异。UPLC-MS/MS方法在2 ~ 2000 ng mL−1范围内线性良好，其中r > 0.99;精密度、准确度、回收率、基质效应和稳定性结果均符合生物样品检测方法的要求。为基础研究提供科学的实验依据。计算了大鼠血浆中苦杏仁碱和乌苏胺的生物利用度，分别为43.5%和19.5%。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Accounts of Chemical Research 化学-化学综合

CiteScore

31.40

自引率

1.10%

发文量

312

审稿时长

2 months

期刊介绍： Accounts of Chemical Research presents short, concise and critical articles offering easy-to-read overviews of basic research and applications in all areas of chemistry and biochemistry. These short reviews focus on research from the author’s own laboratory and are designed to teach the reader about a research project. In addition, Accounts of Chemical Research publishes commentaries that give an informed opinion on a current research problem. Special Issues online are devoted to a single topic of unusual activity and significance. Accounts of Chemical Research replaces the traditional article abstract with an article "Conspectus." These entries synopsize the research affording the reader a closer look at the content and significance of an article. Through this provision of a more detailed description of the article contents, the Conspectus enhances the article's discoverability by search engines and the exposure for the research.