IF 1.8 4区 医学 Q4 BIOCHEMICAL RESEARCH METHODS
Guofang Bi, Qingqing Yu, Jiayin Guo, Shuqing Zhang, Peng Wang, Xiaowen Jiang, Chenghua Wu, Shuang Hu, Xiao Yang, Jian-Hong Fang, Yuhua Long, Huichang Bi
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引用次数: 0

摘要

化合物 13b 是一种新发现的蒽醌衍生物,已证明对寨卡病毒有很强的疗效。为了探索化合物 13b 的生物利用度和药代动力学特性,我们建立并验证了一种稳健灵敏的 HPLC-MS/MS 方法,用于测定其在大鼠体内的血浆浓度。样品制备包括使用乙腈沉淀蛋白质,并以睾酮作为内标。样品分离采用 Phenomenex Kinetex XB-C18 色谱柱(2.1 × 100 mm,2.6 μm),梯度洗脱。流动相由水和乙腈组成,流速为 1 mL/min。采用多反应监测模式(MRM)检测化合物 13b 和睾酮,其电离跃迁分别为 m/z 410.2 → 91.1 和 m/z 289.2 → 109.2。该方法在 2 至 400 纳克/毫升的大鼠血浆样品中表现出良好的线性关系,符合美国食品药品管理局关于生物分析方法验证的所有准则。大鼠服用化合物 13b 14 mg/kg 后,采用非室动力学方法计算了药代动力学特性,发现其绝对口服生物利用度为 15.45%。因此,我们成功地开发了一种高灵敏度、快速测定大鼠血浆中化合物 13b 浓度的 HPLC-MS/MS 方法,并对该方法进行了严格的验证,随后将其用于生物利用度和药代动力学研究。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Development and Validation of a HPLC-MS/MS Method for the Determination of Compound 13b in Rat Plasma and Its Application to a Pharmacokinetic Study

Compound 13b, a newly identified anthraquinone derivative, has demonstrated potent efficacy against the Zika virus. To explore the bioavailability and pharmacokinetic properties of compound 13b, a robust and sensitive HPLC-MS/MS method was established and verified to determine its plasma concentration in rats. Sample preparation involved protein precipitation using acetonitrile with testosterone as an internal standard. A Phenomenex Kinetex XB-C18 column (2.1 × 100 mm, 2.6 μm) was utilized for sample separation with gradient elution. The mobile phase, consisting of water and acetonitrile, was dispensed at a flow rate of 1 mL/min. The multiple reaction monitoring mode (MRM) approach was used to detect compound 13b and testosterone, characterized by their respective ionization transitions: m/z 410.2 → 91.1 and m/z 289.2 → 109.2. The method demonstrated superior linearity within rat plasma samples, ranging from 2 to 400 ng/mL, and met all FDA guidelines for bioanalytical method validation. The pharmacokinetic properties were calculated by non-compartmental approach following administration of compound 13b at 14 mg/kg in rats, and the absolute oral bioavailability was found to be 15.45%. Hence, a highly sensitive and rapid HPLC-MS/MS method for measuring plasma concentration of compound 13b in rats has been successfully developed, rigorously validated, and subsequently utilized in a bioavailability and pharmacokinetic study.

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来源期刊
Biomedical Chromatography
Biomedical Chromatography 生物-分析化学
CiteScore
3.60
自引率
5.60%
发文量
268
审稿时长
2.3 months
期刊介绍: Biomedical Chromatography is devoted to the publication of original papers on the applications of chromatography and allied techniques in the biological and medical sciences. Research papers and review articles cover the methods and techniques relevant to the separation, identification and determination of substances in biochemistry, biotechnology, molecular biology, cell biology, clinical chemistry, pharmacology and related disciplines. These include the analysis of body fluids, cells and tissues, purification of biologically important compounds, pharmaco-kinetics and sequencing methods using HPLC, GC, HPLC-MS, TLC, paper chromatography, affinity chromatography, gel filtration, electrophoresis and related techniques.
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