Cai Yuepiao, Zhang Shuangshuang, Wang Qiqi, Sun Hao, Zhou Mi, Hu Shuping, Xiang Zheng
School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, China.
Planta Med. 2016 Feb;82(3):224-9. doi: 10.1055/s-0035-1558157. Epub 2015 Nov 6.
Nomilin is a potential anticancer agent. In this study, a rapid, sensitive, and simple ultra-performance liquid chromatography with tandem mass spectrometry methodology was established and validated to quantify nomilin in rat plasma. Plasma samples were prepared through liquid-liquid extraction using ethyl acetate. Chromatographic separation was performed using an Acquity HSS T3 column. Acetonitrile and water containing 0.1% (v/v) formic acid were used as mobile phases at a flow rate of 0.3 mL/min. Nomilin and quercetin (internal standard) were detected and quantified via a triple quadrupole tandem mass spectrometer in the positive ion mode with multiple reaction monitoring. Tandem mass spectrometry detection was performed by monitoring the fragmentations of m/z 515.3 → m/z 161.0 and m/z 303.2 → m/z 153.1 of nomilin and quercetin, respectively. Good linearity (R(2) > 0.996) was observed in the concentration range of 1 ng/mL to 500 ng/mL with a lower limit of quantification of 1 ng/mL for nomilin. The average extraction recoveries of nomilin and quercetin were > 82.3% and 82.0%, respectively. Intra- and interday precisions were less than 15% and accuracy ranged from 85.0% to 90.1%. Indeed, the proposed method was successfully applied to analyze the pharmacokinetics of nomilin after 3 and 50 mg/kg nomilin were administered to rats via intravenous and oral routes, respectively.
诺米林是一种潜在的抗癌剂。在本研究中，建立并验证了一种快速、灵敏且简便的超高效液相色谱-串联质谱法，用于定量大鼠血浆中的诺米林。血浆样品通过用乙酸乙酯进行液-液萃取来制备。使用Acquity HSS T3色谱柱进行色谱分离。以含0.1%（v/v）甲酸的乙腈和水作为流动相，流速为0.3 mL/min。通过三重四极杆串联质谱仪在正离子模式下采用多反应监测对诺米林和槲皮素（内标）进行检测和定量。串联质谱检测分别通过监测诺米林的m/z 515.3 → m/z 161.0和槲皮素的m/z 303.2 → m/z 153.1的碎片来进行。在1 ng/mL至500 ng/mL的浓度范围内观察到良好的线性（R(2) > 0.996），诺米林的定量下限为1 ng/mL。诺米林和槲皮素的平均萃取回收率分别> 82.3%和82.0%。日内和日间精密度均小于15%，准确度范围为85.0%至90.1%。实际上，所提出的方法已成功应用于分析分别以3和50 mg/kg的剂量经静脉和口服途径给予大鼠后诺米林的药代动力学。
