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中国临床药理学与治疗学 ›› 2012, Vol. 17 ›› Issue (11): 1206-1210.

• 基础研究 • 上一篇    下一篇

LC-MS/MS快速测定大鼠血浆中HHY-002浓度

王蒙1,2, 周建财2, 张勇2, 孙建国1, 王广基1   

  1. 1中国药科大学药物代谢动力学重点实验室,南京 210009,江苏;
    2合肥合源药业有限公司,合肥 230031,安徽
  • 收稿日期:2012-04-28 修回日期:2012-08-07 发布日期:2012-12-04
  • 通讯作者: 王广基,通信作者,男,博士,博士生导师,教授,研究方向:药物代谢动力学、细胞药代动力学、中药药代动力学研究。Tel: 025-83271128 E-mail: guangjiwang@hotmail.com
  • 作者简介:王蒙,女,硕士研究生,研究方向:药物代谢动力学。Tel: 15855165549 E-mail: gracymile@hotmail.com
  • 基金资助:
    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)

LC-MS/MS determination of HHY-002 in rat plasma

WANG Meng1, 2, ZHOU Jian-cai2, ZHANG Yong2, SUN Jian-guo1, WANG Guang-ji1   

  1. 1Key Laboratory Centre of Drug Metabolism & Pharmacokinetics, China Pharmaceutical University, Nanjing 210009,Jiangsu,China;
    2Hefei Cosource Pharmaceuticals Inc., Hefei 230031, Anhui,China
  • Received:2012-04-28 Revised:2012-08-07 Published:2012-12-04

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 0.200 mL/min,色谱柱Phenomenex Luna C18柱(150 mm×2.00 mm,5 μm,5 micron),进样量为 10 μL,柱温 35 ℃,以地西泮为内标。结果: HHY-002在 1.98~1013.50 ng/mL 的范围内呈良好的线性关系(r=0.998),最低定量限达 1.98 ng/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

Abstract: AIM: A highly sensitive and reliable LC-MS/MS method was validated for the determination of HHY-002 in rat plasma, a novel antiarrhythmic. METHODS: After addition of diazepam as internal standard(IS); LC separation with a Phenomenex Luna C18 analytical column (150 mm×2.00 mm, 5 μm, 5 micron) and quantification by MS/MS after positive ESI. The mobile phase consisted of acetonitrile∶water∶formic acid (65∶35∶0.1, V/V/V) in an isocratic elution mode pumped at 0.200 mL/min, and with the injection volume of 10 μL 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 μL 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 determination of HHY-002 in rat plasma.

Key words: HHY-002, LC-MS/MS, Rat plasma, Anti-arrhythmic

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