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LC-MS/MS快速测定大鼠血浆中HHY-002浓度
引用本文:王蒙,周建财,张勇,孙建国,王广基.LC-MS/MS快速测定大鼠血浆中HHY-002浓度[J].中国临床药理学与治疗学,2012,17(11):1206-1210.
作者姓名:王蒙  周建财  张勇  孙建国  王广基
作者单位:中国药科大学药物代谢动力学重点实验室;合肥合源药业有限公司
基金项目:国家十二五“重大新药创制”科技重大专项资助,企业创新药物孵化基地建设(2011ZX09401-021)
摘    要:目的:建立用于测定治疗慢性心律失常药物HHY-002的大鼠血浆测定法。方法:流动相为乙腈-0.1%甲酸(65:35),流速0.200mL/min,色谱柱Phenomenex LunaC18柱(150mm×2.00mm,5μm,5micron),进样量为10μL,柱温35℃,以地西泮为内标。结果:HHY-002在1.98~1013.50ng/mL的范围内呈良好的线性关系(r=0.998),最低定量限达1.98ng/mL,绝对回收率高于80%,日内和日间误差小于10%,方法回收率大于(81.4±4.5)%,符合生物样品分析要求。结论:建立的LC—MS/MS方法专属性强,灵敏度高,可用于HHY-002的体内定量分析。

关 键 词:HHY-002  LC—MS  MS  大鼠血浆  缓慢  性心律失常

LC-MS/MS determination of HHY-002 in rat plasma
WANG Meng,ZHOU Jian-cai,ZHANG Yong,SUN Jian-guo,WANG Guang-ji.LC-MS/MS determination of HHY-002 in rat plasma[J].Chinese Journal of Clinical Pharmacology and Therapeutics,2012,17(11):1206-1210.
Authors:WANG Meng  ZHOU Jian-cai  ZHANG Yong  SUN Jian-guo  WANG Guang-ji
Institution:1 Key Laboratory Centre of Drug Metabolism & Pharmacokinetics,China Pharmaceutical University,Nanjing 210009,Jiangsu,China;2 Hefei Cosource Pharmaceuticals Inc.,Hefei 230031,Anhui,China
Abstract:AIM: A highly sensitive and relia ble LC-MS/MS method was validated for the de termination of HHY-002 in rat plasma, a novel antiarrhythmic. METHODS: After addition of diazepam as internal standard(IS); LC separa tion with a Phenomenex Luna C18 analytical col umn (150 mm)〈2.00 ram, 5 μm, 5 micron) and quantification by MS/MS after positive ESI. The mobile phase consisted of acetonitrile : wa ter : formic acid (65 : 35 : 0.1, V/V/V) in an isocratic elution mode pumped at 0. 200 mL/ rain, and with the injection volume of 10μ/L and column oven temperature of 35 ℃. RESULTS:The calibration curve ranging from 1.98 to 1013.50 ng/mL. Lower limit of quantification (LLOQ) was 1.98 ng/mL in 100 μ/L of plasma. Extraction recovery was above 80%, inter and intra day accuracy and precise was below 10%. The method recovery was over(81.4±4.5)%. This method was shown to meet all requirements in bioanalytical determination. CONCLUSION: The method was successfully applied to the de termination of HHY-002 in rat plasma.
Keywords:HHY-002  LC-MS/MS  Ratplasma  Anti-arrhythmic
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