Metabolites profile of Xian-Ling-Gu-Bao capsule, a traditional Chinese medicine prescription, in rats by ultra performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry analysis
Metabolites profile of Xian-Ling-Gu-Bao capsule, a traditional Chinese medicine prescription, in rats by ultra performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry analysis
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DOI：
10.1016/j.jpba.2014.03.024
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发表时间：
2014-08-05
影响因子：
3.4
通讯作者：
Yao, Xin-sheng
中科院分区：
文献类型：
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作者：
Geng, Jian-liang;Dai, Yi;Yao, Xin-sheng
仙灵骨葆胶囊是治疗骨质疏松症的常用中药方剂。但由于缺乏代谢方面的研究，其有效成分尚不清楚。这给XLGB的临床安全用药和质量控制带来了巨大的障碍。为了探索XLGB中多个组分的代谢去向，本文提出了基于超高效液相色谱-四极杆飞行时间串联质谱（UPLC/Q-TOF-MS）和质量亏损过滤（mass defect filter）技术的“基于代表性结构的同源异生物质鉴定”（RSBHXI）策略。经口给予XLGB后，在大鼠生物体液中共鉴定或初步表征了147种XLGB相关异生物质，包括血浆中的134种（57种原型组分和77种代谢物），尿液中的93种（37种原型组分和56种代谢物）和胆汁中的118种（46种原型组分和72种代谢物）。结果表明，仙灵脾中的异戊烯化黄酮醇苷、补骨脂中的异戊烯化黄酮、川断和知母中的皂苷以及丹参中的丹参酮是仙灵脾中主要吸收的化学成分。水解、葡萄糖醛酸化和硫酸化是XLGB的主要代谢反应。由于胆汁中检出的外源性物质多于尿液中检出的外源性物质，表明XLGB的多种组分经过了全面的肝胆排泄。本研究拓宽了对XLGB代谢的认识，有助于揭示XLGB在体内的药理物质基础。此外，RSBHXI策略的应用为中药及其他复杂混合物的代谢物鉴定提供了一种新的方法。(C)2014爱思唯尔有限公司版权所有。
Xian-Ling-Gu-Bao capsule (XLGB), a well-known traditional Chinese medicine prescription (TCMP), is widely used for the treatment of osteoporosis. However, due to lack of metabolism research, the effective material of XLGB is still unknown. It entails a huge obstacle for the clinical-safe medication administration and quality control of XLGB. To explore the metabolic fate of multiple components of XLGB, herein, we proposed a "representative structure based homologous xenobiotics identification" (RSBHXI) strategy based on ultra performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry (UPLC/Q-TOF-MS) and mass defect filter (MDF) technique. A total of 147 XLGB-related xenobiotics were identified or tentatively characterized in rat biofluids after oral administration of XLGB, including 134 (57 prototype components and 77 metabolites) in plasma, 93 (37 prototype components and 56 metabolites) in urine and 118 (46 prototype components and 72 metabolites) in bile. Our results indicated that prenylated flavonol glycosides from Herba epimedii, prenylated flavonoids from Fructus psoraleae, saponins from Radix dipsaci and Rhizoma anemarrahenae, as well as tanshinones from Radix Salviae Miltiorrhizae were major absorbed chemical components of XLGB. Hydrolysis, glucuronidation and sulfation were major metabolic reactions of XLGB. As more xenobiotics were detected in bile than those in urine, it demonstrated that multiple components of XLGB underwent comprehensive hepatobiliary excretion. The present study expands our knowledge about the metabolism of XLGB which will be conducive to revealing its in vivo pharmacological material basis. In addition, the application of RSBHXI strategy provides a new approach for metabolite identification of TCMPs and other complex mixture. (C) 2014 Elsevier B.V. All rights reserved.