液相色谱-串联质谱法测定人血浆中马尼地平  

Determination of manidipine in human plasma by LC-MS/MS

作　　者：王晓琳[1] 刘曼[1] 张娅喃[1] 张丽娜[1] 邓鸣[1] 刘会臣[1] WANG Xiaolin;LIU Man;ZHANG Yanan;ZHANG Lina;DENG Ming;LIU Huichen(Department of Clinical Pharmacology,Aerospace Center Hospital,Belying 100049,China)

机构地区：[1]航天中心医院临床药理室,北京100049

出　　处：《国际检验医学杂志》2018年第22期2733-2736,2740,共5页International Journal of Laboratory Medicine

摘　　要：目的建立测定人血浆中马尼地平浓度的液相色谱-串联质谱法。方法 200μL血浆样品经液液萃取后,使用Phenomenex Synergi 4μHydro-RP 80A色谱柱(150mm×2.0mm I.D.),以甲醇-5mmol/L乙酸铵溶液(含0.3%乙酸)为流动相进行梯度洗脱。API 3200型三重四极杆串联质谱仪采用电喷雾离子源、正离子方式检测、多重反应监测(MRM)扫描,马尼地平和尼群地平的离子反应分别为质荷比(m/z)611.1→167.3和m/z 361.1→315.2。方法学验证内容包括选择性、基质效应、线性范围、定量下限、准确度与精密度、提取回收率、血浆/溶液样品稳定性。结果马尼地平和内标尼群地平的保留时间分别约为2.47min和3.03min。马尼地平的线性范围为0.1～16.0ng/mL,低中高浓度质控样品的批内、相对标准偏差均小于15%,相对误差均在±15%以内,平均基质效应因子为(85.0±2.8)%,平均提取回收率为(89.2±4.8)%,血浆/溶液样品在不同保存条件下稳定性良好。结论该方法灵敏耐用,可用于人血浆中马尼地平浓度的测定及马尼地平口服制剂的人体药代动力学研究。Objective To develop a liquid chromatographic tandom mass spectrometric method for the de termination of manidipine in human plasma. Methods The compounds were extracted from 200 μL plasma u sing liquid liquid extraction, and analysis was performed on a Phenomenex Synergi 4 μ Hydro RP 80A column （150 mm× 2.0 mm I. D. ） with gradient mobile phase consisting of methanol 5 mM ammonium acetate （con taining 0.3% acetic acid）. The API 3200 mass spectrometer was equipped with electrospray ionization （ESI） interface and operated in positive ion,multiple reaction monitoring （MRM） mode. The mass transitions moni toted were mass to charge ratio（m/z） 611.1 →167.3 and m/z 361.1 →315.2 for manidipine and nitrendipine, respectively. The validated method was estimated for selectivity,matrix effect, linearity,lower limit of quanti tation,precision and accuracy, recovery, stability. Results The linear calibration curve was obtained over the concentration range of 0.1 16.0 ng/mL. The intra and inter batch relative standard deviation （RSD） were both less than 15~ and relative error （RE） was within ±15%. The mean matrix effect factor was （85. 0± 2.8）%,and the mean extraction recovery was （89.2±4.8）%. Manidipine was found to be stable in plasma and solution under various storage conditions. Conclusion The method was sensitive,robust and suitable for the pharmacokinetic study of manidipine oral formulations in human.

关 键 词：马尼地平 液相色谱-串联质谱法 梯度洗脱 药代动力学 

分 类 号：R969.1[医药卫生—药理学]