下天武注射液穴位给药后大鼠体内主要生物碱的药代动力学和定性代谢产物谱
Pharmacokinetics and qualitative metabolite profiling of major alkaloids in rats after acupoint administration of Xiatianwu Injection.
摘要(中文译文)
夏天无注射液来源于夏天无药材，临床上用于促进血液循环和缓解疼痛。然而，其有效成分和药代动力学特征尚未阐明。在本研究中，通过UPLC-QTOF分析，在夏天无注射液中鉴定出46种成分，包括32种生物碱，其中19种生物碱也在给药后大鼠血浆中被检测到。随后建立了UPLC-QqQ测定方法，用于测定大鼠血浆中的十种生物碱（紫堇达明碱、紫堇杷明碱、非洲防己碱、药根碱、巴马汀、四氢巴马汀、原阿片碱、别隐品碱、穆拉明碱、毕扣扣灵）。色谱分离在ACQUITY UPLC HSS T3柱上完成，以0.1%甲酸水溶液和乙腈作为流动相。该方法表现出令人满意的选择性、线性、基质效应、精密度、准确度和稀释完整性，且样品显示出足够的稳定性。该验证方法成功应用于夏天无注射液三个剂量穴位给药后大鼠的药代动力学研究。研究揭示大多数被定量的生物碱被迅速吸收。C和AUC与剂量呈正相关。原阿片碱、四氢巴马汀和毕扣扣灵显示出较高的血浆暴露量，而四氢巴马汀、紫堇杷明碱和毕扣扣灵表现出较高的剂量归一化C和AUC。通过UPLC-QTOF在大鼠血浆、尿液、胆汁和粪便中初步鉴定了高暴露生物碱（原阿片碱、四氢巴马汀和毕扣扣灵）的代谢物，分别注释出19、25和7种代谢物，主要通过O-去甲基化、去亚甲二氧基化或羟基化形成，随后发生葡萄糖醛酸化或硫酸化。本研究将有助于阐明潜在活性成分、药理机制，并为剂量优化提供依据。
Abstract
Xiatianwu (XTW) Injection, derived from Corydalis Decumbentis Rhizoma, is clinically utilized to promote circulation and alleviate pain. However, its effective components and pharmacokinetic profile have yet to be elucidated. In the present study, 46 components, including 32 alkaloids, were identified in XTW Injection, of which 19 alkaloids were also detected in post-dose rat plasma by UPLC-QTOF analysis. Then a UPLC-QqQ assay was developed to determine ten alkaloids (corydalmine, corypalmine, columbamine, jatrorrhizine, palmatine, tetrahydropalmatine, protopine, allocryptopine, muramine, bicuculline) in rat plasma. Chromatographic separation was achieved on an ACQUITY UPLC HSS T3 column with 0.1% formic acid in water and acetonitrile as the mobile phases. The method showed satisfactory selectivity, linearity, matrix effects, precision, accuracy, and dilution integrity, and the samples showed sufficient stability. The validated method was successfully applied to the pharmacokinetic study in rats after acupoint administration of XTW Injection at three doses. The study revealed that most quantified alkaloids were rapidly absorbed. The C and AUC were positively related to the doses. Protopine, tetrahydropalmatine, and bicuculline showed higher plasma exposure, while tetrahydropalmatine, corypalmine and bicuculline exhibited higher dose-normalized C and AUC. Metabolites of the higher-exposure alkaloids (protopine, tetrahydropalmatine, and bicuculline) were tentatively identified by UPLC-QTOF in rat plasma, urine, bile, and feces, with 19, 25, and 7 annotated metabolites, respectively, formed mainly via O-demethylation, demethylenation, or hydroxylation, followed by glucuronidation or sulfation. This study will contribute to elucidating potential active components, the pharmacological mechanisms, and providing a basis for dose optimization.
如何引用
AMA
Hengbin Zhang, Yuyang Zhao, Hui Liu, Jiayu Yu, Kongsong Wu, Yaodong Yi, et al. Pharmacokinetics and qualitative metabolite profiling of major alkaloids in rats after acupoint administration of Xiatianwu Injection.. Journal of pharmaceutical and biomedical analysis. 2026; doi:10.1016/j.jpba.2026.117536.
APA
Hengbin Zhang, Yuyang Zhao, Hui Liu, Jiayu Yu, Kongsong Wu, Yaodong Yi, et al (2026). Pharmacokinetics and qualitative metabolite profiling of major alkaloids in rats after acupoint administration of Xiatianwu Injection.. Journal of pharmaceutical and biomedical analysis. https://doi.org/10.1016/j.jpba.2026.117536
GB/T 7714
Hengbin Zhang, Yuyang Zhao, Hui Liu, Jiayu Yu, Kongsong Wu, Yaodong Yi, et al. Pharmacokinetics and qualitative metabolite profiling of major alkaloids in rats after acupoint administration of Xiatianwu Injection.[J]. Journal of pharmaceutical and biomedical analysis, 2026 doi:10.1016/j.jpba.2026.117536.
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