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不同炮制品附片(制川乌)煎煮提取物中 6 种乌头碱型生物碱的比较分析及在大鼠体内的药代动力学行为研究。

Comparative analysis of six aconitine-type alkaloids in decocting extracts between the different processed Fuzi (Aconiti Lateralis Radix praeparata) and its pharmacokinetic behavior in rats by HPLC-MS/MS.

机构信息

School of Pharmaceutical Sciences, Hubei University of Medicine, Shiyan, 442000, China.

Sinopharm Dongfeng General Hospital, Hubei University of Medicine, Shiyan, 442008, China.

出版信息

Biomed Chromatogr. 2024 Dec;38(12):e6035. doi: 10.1002/bmc.6035. Epub 2024 Oct 28.

DOI:10.1002/bmc.6035
PMID:39466972
Abstract

Aconiti Lateralis Radix praeparata (also known as Fuzi in Chinese) has been extensively used in clinic. However, the toxicity issues limit the therapeutic range of Fuzi. Thus, a rapid and sensitive HPLC-MS/MS method was developed to simultaneously quantify and compare six active/toxic constituents in decocting extracts from four different processed Fuzi products and in rat plasma after oral administration of its decocting extracts. The selectivity, linearity, sensitivity, precisions, accuracy, matrix effects, extraction recoveries, and stability were validated. The comparative analysis of six alkaloids in decocting extracts between the four kinds of Fuzi products were conducted by the validated HPLC-MS/MS. Principal component analysis (PCA) and orthogonal partial least-squares discriminate analysis (OPLS-DA) were adopted to compare the differences of decocting extracts from the different processed Fuzi products. Besides, selecting Heishunpian (HSP) as the representative of the processed Fuzi products, we investigated the pharmacokinetic behaviors of these major alkaloids after oral administration. The developed HPLC-MS/MS method to simultaneously analyze these aconitine-type alkaloids in decocting extracts, and its pharmacokinetic behavior after oral administration may pave a way for quality control of Fuzi and monitoring the safety and rationality of clinical prescriptions.

摘要

制川乌(也称为附子)在临床上被广泛应用。然而,其毒性问题限制了其治疗范围。因此,建立了一种快速灵敏的 HPLC-MS/MS 方法,用于同时定量和比较四种不同炮制附子产品的煎煮提取物以及口服其煎煮提取物后大鼠血浆中的 6 种活性/毒性成分。对选择性、线性、灵敏度、精密度、准确度、基质效应、提取回收率和稳定性进行了验证。采用已验证的 HPLC-MS/MS 对四种附子产品煎煮提取物中的 6 种生物碱进行了比较分析。采用主成分分析(PCA)和正交偏最小二乘判别分析(OPLS-DA)对不同炮制附子产品的煎煮提取物进行了比较。此外,选择黑顺片(HSP)作为炮制附子产品的代表,研究了这些主要生物碱口服给药后的药代动力学行为。该方法可用于同时分析煎煮提取物中的这些乌头类生物碱,以及口服给药后的药代动力学行为,为附子的质量控制和监测临床处方的安全性和合理性提供了一种方法。

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