散结镇痛胶囊中10种主要成分在大鼠体内的药动学研究

Pharmacokinetics of the main components of Sanjie Zhentong Capsules in rats

摘要

目的: 采用超高效液相色谱-三重四极杆质谱联用(UPLC-TQ-MS/MS)技术,建立大鼠血浆样品中10个成分同时定量的分析方法,评估服用散结镇痛胶囊后主要成分的药动学特征。方法: 大鼠分别灌胃给予1.73、2.59、3.89 g·kg^－1散结镇痛胶囊内容物,检测不同给药时间点大鼠血浆中10个成分的含量,运用非房室模型分析药动学参数。结果: 经系统的方法学验证,10个成分的线性关系良好(r＞0.99),批内、批间的准确度分别为85.3%~113.8%和91.6%~109.9%,提取回收率和基质效应的RSD均＜15%,均符合生物样品的测定要求,表明该方法专属性强、灵敏度高、准确性和稳定性好。药动学结果表明,10个成分中龙血素D和紫檀芪的血浆暴露量较高,龙血素C、龙血素D、7,4′-二羟基黄酮、白藜芦醇和紫檀芪的血浆暴露量和达峰浓度C_max均与剂量呈良好的正相关性(R²>0.91)。除人参皂苷Rd在体内停留时间较长外,其他9个成分在体内吸收迅速且消除较快。结论: 本研究建立大鼠血浆中10个成分的定量分析方法,发现在1.73~3.89 g·kg^－1剂量范围内散结镇痛胶囊中5个成分在大鼠体内呈线性动力学特征,进一步阐明该制剂的药效物质基础和临床用药的合理性,为其临床应用和质量标准提升提供数据支撑。

Abstract

Objective: To establish an ultra-performance liquid chromatography-tandem triple quadrupole mass spectrometry (UPLC-TQ-MS/MS) method for simultaneous quantification of 10 components in rat plasma samples and investigate the pharmacokinetic characteristics of the main components after oral administration of Sanjie Zhentong Capsules (SZC). Methods: Healthy SD rats were administered the contents of SZC at single doses of 1.73, 2.59, and 3.89 g·kg^－1 by oral gavage. Plasma concentrations of 10 components were measured at different time points and pharmacokinetic parameters were analyzed by using non-compartmental model. Results: After systematic method validation, the 10 components exhibited good linearity (r>0.99). The intra-batch and inter-batch accuracy ranged from 85.3% to 113.8% and 91.6% to 109.9%, respectively. The relative standard deviations (RSDs) of extraction recovery and matrix effects were both below 15%. These results met the requirements of biological sample analysis, demonstrating that the method is specific, sensitive, accurate, and stable, thus suitable for quantifying the target components in plasma. Pharmacokinetic analysis revealed that the plasma exposure of loureirin D and pterostilbene was higher than that of other components, and five components (loureirin C, loureirin D, 7,4′-dihydroxyflavone, resveratrol, and pterostilbene) exhibited strong positive correlations (R²>0.91) between dosage and both AUC_(0-t) and C_max. Except for ginsenoside Rd, which exhibited prolonged retention in vivo, the other nine components demonstrated rapid absorption and fast elimination. Conclusion: This study established a quantitative analysis method for 10 components of SZC in rat plasma. Within the dose range of 1.73~3.89 g·kg^－1, five components of SZC exhibited linear pharmacokinetic characteristics in rats. These findings further clarify the pharmacodynamic material basis of this preparation and support its clinical use, providing data to improve the quality standards.

关键词

散结镇痛胶囊 / UPLC-TQ-MS/MS / 药动学

Key words

Sanjie Zhentong Capsule / UPLC-TQ-MS/MS / pharmacokinetics

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基金资助

江苏省基础研究计划自然科学基金资助项目:前沿引领技术基础研究专项(BK20232014);中药制药过程控制与智能制造技术全国重点实验室定向课题资助项目(SKL2023D01002)