液相色谱串联质谱联用法测定犬血浆中氨氯地平和阿托伐他汀浓度.docVIP

液相色谱-串联质谱联用法测定犬血浆中氨氯地平和阿托伐他汀的赵曦，张彦玲，何颖娜，杨汉煜石药集团药物研究院，河北 石家庄 050051 摘要：建立了LC-MS/MS法同时测定犬血浆中氨氯地平和阿托伐他汀的含量。样品用沉淀蛋白法处理，采用C18柱，流动相为甲醇-2醋酸胺+0.5%甲酸水溶液（68∶32，）流动相，以地西泮为内标，电喷雾离子化，以正离子多离子反应监测（MRM），检测离子分别为m/z409.2( m/z238.1（氨氯地平），m/z559.2( m/z440.5（阿托伐他汀）和m/z285.1( m/z193.1（内标，地西泮）。氨氯地平在0.1~20.0 μg、阿托伐他汀在0.2~50.0 μg浓度范围内线性关系良好，最低定量限氨氯地平为0.1μg、阿托伐他汀为0.2μg，方法回收率均大于94%，日内、日间RSD均小于8.8%。结论：此法专属、灵敏、准确，适用于药物动力学。 [关键词]：氨氯地平；阿托伐他汀；液相色谱-串联质谱法；血药浓度 [中图分类号]： [文献标识码]：A [文章编号]： Determination of Amlodipine and Atorvastatin in Beagle dog′s Plasma by LC-MS/MS YUE Jin，ZHAO Xi， ZHANG Yan-ling ，HE Ying-na，YANG Han-yu* (Pharmaceutical Research Institute of Shijiazhuang Pharmaceutical Group Co.,Ltd.，Shijiazhuang 050051) A: OBJECTIVE：A LC-MS/MS method was established for the determination of amlodipine and atorvastatin in Beagle dog′s plasma. METHORDS： The samples were precipitated with methanol. A C18 column was used with the mobile phase of methanol-2mmol·L-1+0.5%formic acid (68∶32,).Diazepam was used as internal standard. ESI was applied and operated in positive ion mode. The detected ions were m/z409.2→ m/z238.1(amlodipine), m/z559.2→ m/z440.5(atorvastatin) and m/z285.1→m/z193.1(diazepam). RESULTS：The calibration curve was linear in the range of 0.1~20.0 μg·L-1 (amlodipine) and 0.2 ~50.0 μg·L-1 (atorvastatin),respectively.The low limit of quantification was 0.1μg·L-1 (amlodipine) and 0.2 μg·L-1 (atorvastatin),respectively.The average recovery was more than 94%. The RSDs of intra- and inter-day were all less than8.8 %. Conclusion：The method was proved to be specific, sensitive and accurate, and suitable for clinical pharmacokinetics studies of cefaclor. KEY WORDS：amlodipine；atorvastatin；LC/MS/MS；plasma concentration CADUET是抗高血压药氨氯地平（Amlodipine，）和降脂药阿托伐他汀（Atorvastatin，）混合而的制剂。该药物同时患有高血压和高脂血症的患者，可以有效控制血压和血脂水平，提高服药的顺应性，有效治疗和预防心血管系统疾病的发生，同时低患心脏病的风险。由于该复方产品具有良好的疗效，因此对其进行了大量的研究，临床前及临床药代动力学研究需要，要求建立一种有效的分析方法。 目前已有文献报道采用HPLC法、LC-MS法分别测定或的浓度[1~6]。本研究建立了LC-MS/MS法同时测定血浆样品中和两种组分的含量，该方法专属性强、