Hydrophilic interaction liquid chromatography-tandem mass spectrometry analysis of oligosaccharides and iridoid glycosides in rat plasma: Pharmacokinetic characterization of previously overlooked oligosaccharides from Radix Rehmanniae

IF 3.1 3区医学 Q2 CHEMISTRY, ANALYTICAL

Journal of pharmaceutical and biomedical analysis Pub Date : 2025-01-09 DOI:10.1016/j.jpba.2025.116670

Hanyang Wang , Yue Du , Chunwei Zhou , Yan Wang , Xin Wang

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Abstract

Radix Rehmanniae (RR) is a widely used herb in traditional Chinese Medicine with properties of tonifying the kidneys and nourishing the blood. Both raw and processed RR are effective for the treatment of diabetes in clinical practice. Oligosaccharides and iridoid glycosides are the primary active components responsible for the anti-diabetic effects of RR. In this study, a rapid and sensitive hydrophilic interaction liquid chromatography-tandem mass spectrometry (HILIC−MS/MS) method was developed for simultaneous determination of oligosaccharides (raffinose, manninotriose and stachyose) and iridoid glycosides (catalpol and ajugol) in rat plasma. Significant analytical challenges were encountered during method development, including distinct retention behaviors of oligosaccharides and iridoid glycosides, low ionization and extraction efficiency of oligosaccharides, thermal instability of catalpol and reduced column performance. The strategies to overcome these challenges were presented by optimizing chromatographic separation, mass spectrometric detection and sample preparation. The best separation was achieved using an Accucore-150-Amide-HILIC column (100 mm × 2.1 mm, 2.6 μm) at 50 °C with mobile phase consisted of acetonitrile and ammonium acetate (2.5 mM) under gradient elution. Ammonium adduct ions produced by positive electrospray ionization were chosen as precursor ions for multiple reaction monitoring transitions. The established HILIC−MS/MS method exhibited good linearity (r > 0.9937) with the lower limits of quantification of 0.01–0.2 μg/mL using only 50 µL of plasma sample. The method was successfully applied to pharmacokinetic characterization of oligosaccharides and iridoid glycosides in normal and type 2 diabetic rats following intragastric administration of raw and processed RR extracts.

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大鼠血浆中低聚糖和环烯醚萜苷的亲水相互作用-液相色谱-串联质谱分析：以前被忽视的地黄低聚糖的药代动力学表征。

地黄（RR）是一种广泛使用的中药，具有补肾养血的特性。在临床实践中，生的和加工的红霉素对糖尿病的治疗都是有效的。低聚糖和环烯醚萜苷是RR抗糖尿病作用的主要活性成分。本研究建立了快速、灵敏的亲水相互作用液相色谱-串联质谱（HILIC-MS/MS）同时测定大鼠血浆中低聚糖（棉子糖、甘露糖和水苏糖）和环烯醚萜苷（catalpol和ajugol）的方法。在方法开发过程中遇到了重大的分析挑战，包括低聚糖和环烯醚萜苷的独特保留行为，低聚糖的低电离和提取效率，catalpol的热不稳定性以及色谱柱性能降低。通过优化色谱分离、质谱检测和样品制备，提出了克服这些挑战的策略。Accucore-150-Amide-HILIC色谱柱（100 mm × 2.1 mm, 2.6 μm），温度为50 °C，流动相为乙腈和乙酸铵（2.5 mm），梯度洗脱，分离效果最佳。采用正电喷雾电离产生的铵加合物离子作为前体离子，用于多反应监测跃迁。所建立的HILIC-MS/MS方法具有良好的线性关系（r > 0.9937），定量下限为0.01 ~ 0.2 μg/mL，仅需50 µL血浆样品。该方法成功地应用于正常和2型糖尿病大鼠灌胃RR提取物后低聚糖和环烯醚萜苷的药动学表征。

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来源期刊

Journal of pharmaceutical and biomedical analysis 医学-分析化学

CiteScore

6.70

自引率

5.90%

发文量

588

审稿时长

37 days

期刊介绍： This journal is an international medium directed towards the needs of academic, clinical, government and industrial analysis by publishing original research reports and critical reviews on pharmaceutical and biomedical analysis. It covers the interdisciplinary aspects of analysis in the pharmaceutical, biomedical and clinical sciences, including developments in analytical methodology, instrumentation, computation and interpretation. Submissions on novel applications focusing on drug purity and stability studies, pharmacokinetics, therapeutic monitoring, metabolic profiling; drug-related aspects of analytical biochemistry and forensic toxicology; quality assurance in the pharmaceutical industry are also welcome. Studies from areas of well established and poorly selective methods, such as UV-VIS spectrophotometry (including derivative and multi-wavelength measurements), basic electroanalytical (potentiometric, polarographic and voltammetric) methods, fluorimetry, flow-injection analysis, etc. are accepted for publication in exceptional cases only, if a unique and substantial advantage over presently known systems is demonstrated. The same applies to the assay of simple drug formulations by any kind of methods and the determination of drugs in biological samples based merely on spiked samples. Drug purity/stability studies should contain information on the structure elucidation of the impurities/degradants.