丹酚酸B及其代谢物丹参素在正常和肾纤维化小鼠体内的药动学和肾暴露比较研究

IF 1.8 4区 医学 Q4 BIOCHEMICAL RESEARCH METHODS
Pinglan Lin, Fengling Li, Bin Zou, Jing Zhao, Guochao Song, Fengyi Weng, Chen Wang, Jingyi Jin, Furong Qiu
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引用次数: 0

摘要

丹参中的水溶性化合物丹酚酸B (Salvianolic acid B, SAB)被广泛用于治疗肾纤维化。本研究旨在探讨注射用丹参去脂盐(SDSI)或SAB在正常小鼠和单侧输尿管梗阻(UUO)小鼠体内的药代动力学。建立了同时测定生物样品中SAB和DSS的LC-MS/MS方法。验证结果表明,该方法的线性度、准确度和精密度、基质效应和回收率、稳定性均满足FDA生物分析指南的要求。药代动力学研究表明,假手术组SAB组小鼠血浆和肾脏SAB暴露量高于SDSI组,而DSS组则低于SDSI组。与假手术组比较,UUO组梗阻肾(OKs)和未梗阻肾(NOKs)中SAB的AUC0-t分别下降71.14%和54.63%。与假手术组相比,UUO组OKs和NOKs的DSS AUC0-t分别升高60.8%和177.79%。该方法已成功应用于SAB和DSS的生物分析。本研究为SAB的合理临床应用提供药代动力学支持。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Comparative Study of Pharmacokinetics and Renal Exposure of Salvianolic Acid B and Its Metabolite Danshensu in Normal and Renal Fibrosis Mice

Salvianolic acid B (SAB), a water-soluble compound in Salvia miltiorrhiza (Danshen), has been widely used in the treatment of renal fibrosis. This study aimed to investigate the pharmacokinetics of SAB and its active metabolite danshensu (DSS) after intraperitoneal injection of Salvia miltiorrhiza depside salt for injection (SDSI) or SAB in normal and unilateral ureteric obstruction (UUO) mice. An LC-MS/MS method was developed to simultaneously determine the SAB and DSS in biological samples. The validation results showed that the linearity, accuracy and precision, matrix effects and recovery, and stability satisfied the FDA bioanalysis guidelines. Pharmacokinetic study showed that plasma and renal exposure of SAB in mice administered SAB were higher than that in mice administered SDSI in the sham group, while those of DSS were lower. Compared with the sham group, the AUC0-t of SAB in obstructed kidneys (OKs) and non-obstructed kidneys (NOKs) of the UUO group decreased by 71.14% and 54.63%, respectively. The AUC0-t of DSS in the OKs and NOKs of the UUO group increased by 60.8% and 177.79%, respectively, compared with the sham group. Developed method was successfully applied to the bioanalysis of SAB and DSS. Our study provides pharmacokinetic support for the rational clinical application of SAB.

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来源期刊
Biomedical Chromatography
Biomedical Chromatography 生物-分析化学
CiteScore
3.60
自引率
5.60%
发文量
268
审稿时长
2.3 months
期刊介绍: Biomedical Chromatography is devoted to the publication of original papers on the applications of chromatography and allied techniques in the biological and medical sciences. Research papers and review articles cover the methods and techniques relevant to the separation, identification and determination of substances in biochemistry, biotechnology, molecular biology, cell biology, clinical chemistry, pharmacology and related disciplines. These include the analysis of body fluids, cells and tissues, purification of biologically important compounds, pharmaco-kinetics and sequencing methods using HPLC, GC, HPLC-MS, TLC, paper chromatography, affinity chromatography, gel filtration, electrophoresis and related techniques.
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