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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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.