UHPLC-MS/MS-Based Quantification of 14 Renshen Guben Oral Liquid-Related Constituents in Cancer Patients With Neutropenia.

IF 2.9 3区 生物学 Q2 BIOCHEMICAL RESEARCH METHODS
Mengyuan Wu, Zhaojie Ji, Yanjiang Dong, Sitong Liu, Shuo Diao, Xintong Wang, Ju Zhao, Boya Zhang, Da Rong, Wenxin Xu, Enli Wang, Rui Niu, He Xiao, Mingming Yu, Zhihua Lv, Sherwin K B Sy, Hai Yang
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Abstract

Objectives: This study aimed to develop and validate a UHPLC-MS/MS method for the simultaneous determination of 14 constituents related to Renshen Guben Oral Liquid (RSGB) in human plasma and to explore concentration-absolute neutrophil count (ANC) associations in cancer patients with chemoradiotherapy-induced neutropenia (CIN).

Methods: Candidate constituents were selected by integrating chemical representativeness, disease relevance, reference standard availability, and analytical feasibility, with support from network pharmacology. Plasma samples were collected from 25 patients before administration and at 1 and 2 h after RSGB administration. Samples were processed by liquid-liquid extraction using methyl tert-butyl ether or n-butanol and analyzed by UHPLC-MS/MS. Spearman correlation analysis was used to assess exploratory associations between post-dose concentrations of major quantifiable circulating constituents and ANC change from baseline to Day 15.

Results: The assay fulfilled predefined bioanalytical acceptance criteria and enabled simultaneous quantification of 14 RSGB-related constituents in human plasma. Ginsenoside Rb1 (G-Rb1), ginsenoside compound K (G-CK), and paeonol (PAE) were the major quantifiable circulating constituents, whereas protopanaxadiol (PPD) and protopanaxatriol (PPT) were only sporadically quantifiable. Exploratory analyses showed positive associations between concentrations of G-Rb1, G-CK, and PAE and ΔANC. Molecular docking provided complementary computational support for potential target interactions.

Conclusions: G-Rb1, G-CK, and PAE were the major quantifiable circulating RSGB-related constituents within the early sampling window, and their concentrations showed exploratory associations with ANC change. These findings provide complementary in vivo evidence for evaluating RSGB-related constituents.

基于UHPLC-MS/ ms的肿瘤中性粒细胞减少患者补肾固本口服液中14种相关成分的定量分析
目的:建立UHPLC-MS/MS同时测定人血浆中仁肾固本口服液(RSGB)中14种相关成分的方法,探讨浓度-绝对中性粒细胞计数(ANC)在放化疗诱导的中性粒细胞减少症(CIN)患者中的相关性。方法:在网络药理学的支持下,综合化学代表性、疾病相关性、参考标准可用性和分析可行性,选择候选成分。25例患者在给药前和给药后1、2 h采集血浆样本。样品采用甲基叔丁基醚或正丁醇液-液萃取,UHPLC-MS/MS分析。Spearman相关分析用于评估主要可量化循环成分给药后浓度与基线至第15天ANC变化之间的探索性关联。结果:该方法符合预先设定的生物分析接受标准,并能同时定量人血浆中14种rsgb相关成分。人参皂苷Rb1 (G-Rb1)、人参皂苷化合物K (G-CK)和丹皮酚(PAE)是主要可定量的循环成分,而原人参二醇(PPD)和原人参三醇(PPT)仅少量可定量。探索性分析显示G-Rb1、G-CK和PAE浓度与ΔANC呈正相关。分子对接为潜在的靶标相互作用提供了互补的计算支持。结论:G-Rb1、G-CK和PAE是早期采样窗口内可量化的主要循环rsgb相关成分,其浓度与ANC变化呈探索性相关性。这些发现为评估rsgb相关成分提供了补充的体内证据。
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来源期刊
Phytochemical Analysis
Phytochemical Analysis 生物-分析化学
CiteScore
6.00
自引率
6.10%
发文量
88
审稿时长
1.7 months
期刊介绍: Phytochemical Analysis is devoted to the publication of original articles concerning the development, improvement, validation and/or extension of application of analytical methodology in the plant sciences. The spectrum of coverage is broad, encompassing methods and techniques relevant to the detection (including bio-screening), extraction, separation, purification, identification and quantification of compounds in plant biochemistry, plant cellular and molecular biology, plant biotechnology, the food sciences, agriculture and horticulture. The Journal publishes papers describing significant novelty in the analysis of whole plants (including algae), plant cells, tissues and organs, plant-derived extracts and plant products (including those which have been partially or completely refined for use in the food, agrochemical, pharmaceutical and related industries). All forms of physical, chemical, biochemical, spectroscopic, radiometric, electrometric, chromatographic, metabolomic and chemometric investigations of plant products (monomeric species as well as polymeric molecules such as nucleic acids, proteins, lipids and carbohydrates) are included within the remit of the Journal. Papers dealing with novel methods relating to areas such as data handling/ data mining in plant sciences will also be welcomed.
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