Shandong Provincial Maternal and Child Health Care Hospital Affiliated to Qingdao University, Key Laboratory of Birth Regulation and Control Technology of National Health Commission of China, Jinan 250014, China.
J AOAC Int. 2023 Jul 17;106(4):1010-1016. doi: 10.1093/jaoacint/qsad012.
Skimmin, a potential agent for treating postpartum stroke, is one of the most important coumarins extracted from the leaves of skimmia.
In this study, a specific, sensitive, and simple high-performance liquid chromatography with tandem mass spectrometry (HPLC-MS/MS) method for the simultaneous determination of skimmin and its metabolite umbelliferone in rat plasma was established and validated.
Chromatographic separation was performed by an Inertsil ODS-3 column (50 mm × 4.6 mm, 5 μm) with a mobile phase consisting of 0.1% formic acid in distilled water-acetonitrile at a flow rate of 0.5 mL/min with gradient elution mode. All analytes were detected and quantified in negative multiple reaction monitoring (MRM).
All calibration curves showed good linearity (r > 0.995) over the concentration range of 10-10 000 and 2.0-2000 ng/mL for skimmin and umbelliferone, respectively. The selectivity, sensitivity, extraction recovery, matrix effect, and stability met all requirements.
The analysis method was successfully applied to the pharmacokinetic study of skimmin and umbelliferone in rats following oral administration of skimmin at the doses of 10, 30, and 90 mg/kg. With the exception of AUC(0-∞) and Cmax, MRT and Cl/F of skimmin had significant statistical difference with the increasing doses. Skimmin might exhibit nonlinear pharmacokinetic characteristics in rats.
This was the first study to investigate the pharmacokinetic characteristics of skimmin as a candidate agent for treating postpartum stroke.
skimmin 是一种治疗产后中风的潜在药物，是从瑞香科植物茎叶中提取的最重要香豆素之一。
本研究建立并验证了一种专属性强、灵敏度高、简单的高效液相色谱-串联质谱（HPLC-MS/MS）法，用于同时测定大鼠血浆中的 skimmin 及其代谢产物 Umbelliferone。
色谱分离采用 Inertsil ODS-3 柱（50mm×4.6mm，5μm），以 0.1%甲酸的蒸馏水-乙腈为流动相，梯度洗脱，流速为 0.5mL/min。所有分析物均采用负多重反应监测（MRM）模式检测和定量。
skimmin 和 Umbelliferone 的浓度范围分别为 10-10000 和 2.0-2000ng/mL 时，所有校准曲线均呈良好的线性（r>0.995）。选择性、灵敏度、提取回收率、基质效应和稳定性均符合要求。
该分析方法成功应用于大鼠口服skimmin 10、30 和 90mg/kg 后skimmin 和 Umbelliferone 的药代动力学研究。除 AUC（0-∞）和 Cmax 外，skimmin 的 MRT 和 Cl/F 与剂量呈显著统计学差异。skimmin 在大鼠体内可能表现出非线性药代动力学特征。
这是首次研究 skimmin 作为治疗产后中风候选药物的药代动力学特征。
