摘要
目的采用高效液相色谱-串联质谱（LC．MS／MS）法建立同时检测人血浆中奥氮平与拉莫三嗪浓度方法。方法以Agilent EclipseplusC18（100mm×4．6mm，5μm）为分析柱，流动相为含5mmol·L-1甲酸铵的甲醇-水体系（75：25），流速为0．5mL·min-1，以奥氮平．D3及拉莫三嗪-13Q-D3为内标，采用蛋白沉淀法进行样本处理，采用选择性离子监测（MRM），通过三重四级杆串联质谱仪正离子模式同时分析奥氮平（m／z313--→256）与拉莫三嗪（m／z256-→145）血浆浓度，并应用于检测46份临床样本。结果奥氮平在2—200μg·L-1（R0=0．9972）内线性较好，高、中、低浓度质控日内（n=6）及日间（n=3）精密度RSD值均低于7．13％，准确度在97．47％～102．70％内，提取回收率为94．24％，103．31％，102．28％；拉莫三嗪在0．2～25mg·L-1（R2=0．9988）内线性较好，高、中、低浓度日内（n=6）及日间（n=3）精密度RSD值均低于5．56％，准确度在93．97。102．55％内，提取回收率为100．89％、93．66％、91．27％。结论本方法可简便、灵敏、高效测定人血浆中奥氮平与拉莫三嗪血药浓度且特异性好，人血浆内源性杂质不干扰奥氮平和拉莫三嗪的测定。
AIM To develop an LC-MS/MS method for simultaneous determination of olanzapine and lamotrigine in human plasma. METHODS Agilent Eclipse plus Cls column（ 100 mm × 4.6 mm, 5μm） was used to separate the analytes, and the mobile phase was methanol-water（75：25） system containing with 5 mmol· L-1 ammonium format at a flow rate of 0.5 mE·min-1. The olanzapine-D3 and lamotrigine-laC3-O3 were employed as the internal standard,and the hu- man plasma sample was precipitated by methanol. Simultaneously detecting the plasma drug concentration of olanzapine （m/z 313→256）and lamotrigine （m/z 256→145 ） was performed with multiple reactions monitoring（MRM）using posi- tive eletrospray ionization（ESI）by triple quadmpole mass spectrometer. RESULTS The calibration curves for olanzapine had good linearity （R2 = 0.997 2, n = 7）within the range of 2- 200μg·L-1. The high, medium and low concentration RSD of inter- and intra-day precisions were less than 7.13% and accuracy was between 97.47% and 102.70%. The extraction recoveries of olanzapine were 94.24%, 103.31% and 102.28%, respectively. The linear calibration curve of lamotrigine had good linearity （R2= 0.998 8, n = 7）within the range of 0.2- 25mg· L-1. The high, medium and low concentration RSD of inter- and intra-day precisions were less than 5.56% and accuracy was within 93.97% - 102.55 %. The extraction recoveries of olanzapine were 100.89 %, 93.66% and 91.27 % respectively. CONCLUSION This method is simple, sensitive and efficient to simultaneously detect olanzapine and lamotrigine in human plasma with good specificity, and the internal impurity doesn＇t interfere with the simultaneously determination of olanzapine and lamot- rigin.
出处
《中国临床药学杂志》
CAS
2016年第5期278-282,共5页
Chinese Journal of Clinical Pharmacy
基金
国家自然科学基金(编号81403016)
广州市医药卫生科技项目(编号20141A011041)
广东省自然科学基金(编号2015A030313808)
