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Developing an UPLC-MS/MS method to quantify maoecrystal A in rat plasma: Application to a pharmacokinetic study
Journal of Chromatography B ( IF 2.8 ) Pub Date : 2018-04-10
Chenning Zhang, Caibin Qin, Guangyi Yang, Fadia Boughaba, Yue He, Weidong Ma, Yonghong Zhang, Song Gao

Maoecrystal A (MC-A) is an ent-kaurane-type diterpene isolated from Rabdosia eriocalyx (Dunn) Hara. MC-A has been reported to show different pharmacological activities, including anticancer, anti-inflammatory and bacteriostatic functions. However, bioanalysis of MC-A has not been reported. The purpose of this study is to develop an UPLC-MS/MS method to quantify MC-A in plasma and determine its pharmacokinetic properties using an animal model. The separation was performed using a Waters HSS T3 column (50 mm × 2.1 mm, 1.8 μm, Waters Corp., Milford, MA, USA) with methanol and water containing 0.1% of formic acid as the mobile phases. The mass analysis was performed in a Waters Xevo TQ mass spectrometer using multiple reaction monitoring (MRM) in positive scan mode. Protein precipitation was used to extract the drug from rat plasma samples. The calibration curve is linear in the concentration range 0.49–2000.0 ng/mL. The extraction recovery and the matrix effect were 78.11 to 91.72% and 90.38 to 98.02%, respectively. The RSD of inter/intra-day precisions were <13.72% and the accuracy was >86.41%. Stability studies showed that MC-A was stable (RSD < 14.98%) at different conditions (i.e., short-term, long-term, bench, and three freeze-thaw cycles) in rat plasma. The method was successfully applied to a pharmacokinetic study using rats through oral and intravenous administration routes. The oral bioavailability of MC-A was only 2.9%. Further studies are needed to investigate the absorption and metabolism in order to improve the oral bioavailability of MC-A.



中文翻译:

开发UPLC-MS / MS方法定量大鼠血浆中的毛晶A:在药代动力学研究中的应用

Maoecrystal A(MC-A)是分离自一个ENT-贝壳杉烷类双萜冬凌草eriocalyx(邓恩)哈拉。据报道,MC-A显示出不同的药理活性,包括抗癌,抗炎和抑菌功能。然而,尚未报道MC-A的生物分析。这项研究的目的是开发一种UPLC-MS / MS方法来定量测定血浆中的MC-A并使用动物模型确定其药代动力学特性。使用Waters HSS T3色谱柱(50 mm×2.1 mm,1.8μm,Waters Corp.,Milford,MA,美国)进行分离,其中甲醇和水含有0.1%的甲酸作为流动相。质量分析是在Waters Xevo TQ质谱仪中以正扫描模式使用多反应监测(MRM)进行的。蛋白沉淀用于从大鼠血浆样品中提取药物。在0.49–2000.0 ng / mL的浓度范围内,校准曲线是线性的。提取回收率和基质效应分别为78.11%至91.72%和90.38%至98.02%。日间/日内精度的RSD小于13.72%,精度大于86.41%。稳定性研究表明,MC-A在不同条件下均稳定(RSD <14.98%)((例如短期,长期,卧推和三个冻融循环)大鼠血浆中。该方法已成功应用于大鼠通过口服和静脉内给药途径进行的药代动力学研究。MC-A的口服生物利用度仅为2.9%。需要进一步的研究来研究其吸收和代谢,以改善MC-A的口服生物利用度。

更新日期:2018-04-10
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