Improved Protective Effects and Pharmacokinetics of Huperzine A Derivative H14 in Soman Poisoning: A Comparative Study With Huperzine A in Rats

IF 1.8 3区化学 Q4 BIOCHEMICAL RESEARCH METHODS

Rapid Communications in Mass Spectrometry Pub Date : 2025-02-15 DOI:10.1002/rcm.9995

Guixiang Yang, Yalan Cui, Xingxing Zong, Qian Jin, Yi Zhang, Liqin Li, Dongxin Liu, Xuejun Chen, Chen Wang, Jingchen Wei

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引用次数: 0

Abstract

Rationale

N-[2-Hydroxy-3,5-dimethylbenzilidene]-Hup A (H14) is a derivative of huperzine A (Hup A) that demonstrates superior protective effects against soman (GD) compared to Hup A. This study aims to evaluate the protective efficacy of H14 pretreatment against GD in rats and to provide an analytical framework for the pharmacokinetic evaluation of H14 in experimental animals.

Methods

The study employed protective ratios (PR) as an evaluation criterion to assess the efficacy of H14 and Hup A in preventing GD in vivo. Liquid–liquid extraction techniques were utilized to extract H14 and its metabolite, Hup A, from plasma. The extracted plasma samples were then analyzed using an ultra-high-performance liquid chromatography–tandem mass spectrometry (UHPLC–MS/MS) method for the simultaneous quantification of H14 and Hup A.

Results

The PR values for the 6- and 12-h Hup A groups were 1.26 and 1.08, respectively. In contrast, the 6, 12, and 24-h H14 groups demonstrated PR values of 2.81, 1.98, and 1.18, respectively, indicating extended protective capabilities compared to Hup A. All validation parameters for the UHPLC–MS/MS method, including linearity, specificity, precision, accuracy, matrix effect, and stability, met the acceptance criteria established by FDA guidelines. The pharmacokinetic analysis indicates that H14, after conversion to Hup A in vivo, significantly extends the duration of Hup A concentrations in the body, leading to more effective prevention of GD poisoning compared to Hup A alone.

Conclusions

H14 demonstrates superior efficacy in preventing GD poisoning compared to Hup A. Furthermore, this analytical approach offers a reliable and efficient method for the pharmacokinetic evaluation of H14 in experimental animals.

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石杉碱A衍生物H14对索曼中毒的保护作用及药动学研究：与石杉碱A的比较研究

N-[2-羟基-3,5-二甲基苄基]-Hup A （H14）是石杉碱A （Hup A）的衍生物，对索曼（GD）的保护作用优于Hup A。本研究旨在评价H14预处理对大鼠索曼（GD）的保护作用，并为H14在实验动物体内的药代动力学评价提供分析框架。方法以保护比（PR）为评价标准，评价H14和Hup A在体内预防GD的效果。采用液-液萃取技术从血浆中提取H14及其代谢物Hup A。提取的血浆样品采用超高效液相色谱-串联质谱法（UHPLC-MS /MS）同时定量H14和Hup A。结果6 h和12 h Hup A组的PR值分别为1.26和1.08。相比之下，6、12和24 h H14组的PR值分别为2.81、1.98和1.18，表明与Hup a相比，保护能力更强。UHPLC-MS /MS方法的所有验证参数，包括线性、特异性、精密度、准确度、基质效应和稳定性，均符合FDA指南制定的可接受标准。药代动力学分析表明，H14在体内转化为Hup A后，显著延长了Hup A在体内浓度的持续时间，比单独使用Hup A更有效地预防GD中毒。结论H14对GD中毒的预防效果优于Hup a，该分析方法为H14在实验动物体内的药动学评价提供了可靠、高效的方法。

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

Rapid Communications in Mass Spectrometry 化学-分析化学

CiteScore

4.10

自引率

5.00%

发文量

219

审稿时长

2.6 months

期刊介绍： Rapid Communications in Mass Spectrometry is a journal whose aim is the rapid publication of original research results and ideas on all aspects of the science of gas-phase ions; it covers all the associated scientific disciplines. There is no formal limit on paper length ("rapid" is not synonymous with "brief"), but papers should be of a length that is commensurate with the importance and complexity of the results being reported. Contributions may be theoretical or practical in nature; they may deal with methods, techniques and applications, or with the interpretation of results; they may cover any area in science that depends directly on measurements made upon gaseous ions or that is associated with such measurements.