A sensitive, high-throughput, and eco-friendly analysis of daidzein and its valine carbamate prodrug in rat plasma by supercritical fluid chromatography with tandem mass spectrometry
A sensitive, high-throughput, and eco-friendly analysis of daidzein and its valine carbamate prodrug in rat plasma by supercritical fluid chromatography with tandem mass spectrometry
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采用超临界流体色谱-串联质谱法对大鼠血浆中的大豆黄酮及其缬氨酸氨基甲酸酯前药进行灵敏、高通量且环保的分析
DOI：
10.1002/jssc.201800430
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发表时间：
2018
影响因子：
3.1
通讯作者：
Tianhong Zhang
中科院分区：
文献类型：
--
作者：
Yingchao Li;Xingxing Zhang;Xiaochen Bai;Xiaoting Li;Qikun Jiang;Tianhong Zhang
针对大豆苷元溶解性差、渗透性差的特点，合成了一种大豆苷元缬氨酸氨基甲酸酯前药，以提高其生物利用度。为评价大豆苷元前体药物的药动学行为，建立了一种灵敏、高通量的同时测定大鼠血浆中大豆苷元及其前体药物的方法。样品用乙酸乙酯提取，然后用超临界流体色谱-电喷雾串联质谱法进行分析。采用ACQUITY UPC 2 TM BEH 2-EP色谱柱，在40 ℃下，以二氧化碳（≥99.99%）和甲醇梯度洗脱，在3.0 min内实现分离。大豆苷元、前体药物和染料木素的质量跃迁离子对分别为m/z 254.8→136.7、398.0→254.9和271.0→91.07。大豆苷元和前体药物的线性范围分别为2-500（r > 0.997）和10.0-5000.0 ng/mL（r > 0.996），定量下限分别为2和10 ng/mL。所有质控样品的日内和日间准确度和精密度均在±15%范围内。该方法特异性强、成本低、溶剂消耗少、分析时间短，已成功应用于大豆苷元及其氨基甲酸酯前体药物的生物利用度评价。
A valine carbamate prodrug of daidzein was synthesized to improve its bioavailability because of the poor solubility and low permeability of daidzein. To evaluate the pharmacokinetic behavior of the prodrug, a sensitive and high-throughput method was developed and validated for the simultaneous determination of daidzein and its prodrug in rat plasma. The samples were extracted by ethyl acetate and then analyzed by a supercritical fluid chromatography with electrospray ionization tandem mass spectrometry method. The separation was achieved by an ACQUITY UPC2TM BEH 2-EP column maintained at 40◦C using carbon dioxide (≥99.99%) and methanol within 3.0 min by gradient elution. The mass transition ion pairs were m/z 254.8→136.7, 398.0→254.9, and 271.0→91.07 for daidzein, the prodrug, and genistein, respectively. The calibration curves were linear over the concentration ranges of 2–500 (r > 0.997) and 10.0–5000.0 ng/mL (r > 0.996) with lower limits of quantification of 2 and 10 ng/mL for daidzein and the prodrug, respectively. The intra- and interday accuracy and precision were within ±15% for all quality control samples. This developed method enabled high specificity, low cost, low solvent consumption, and a brief analysis time and was successfully applied to a bioavailability evaluation of daidzein and its carbamate prodrug.