贵州医科大学学报

2018, v.43;No.219(12) 1425-1429

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液质联用法同时测定人血清中5种非典型抗精神病药物浓度
Simultaneous Determination of 5 Atypical Antipsychotic Drugs in Human Serum by Liquid Chromatography Mass Spectrometry

王玮;余淑珍;彭军;许洪涛;
WANG Wei;YU Shuzhen;PENG Jun;XU Hongtao;Department of Pharmacy,Jiangsu Integrated Traditional Chinese and Western Medicine Hospital;Hangzhou BIOZON Medical Institute Co.,Ltd;

摘要(Abstract):

目的:建立一种快速、准确的超高效液相色谱串联质谱法(UPLC-MS/MS),用于临床上测定人血清中氯氮平、N-去甲基氯氮平、喹硫平、阿立哌唑及齐拉西酮5种常用的非典型抗精神病药物的血药浓度。方法:以氯氮平-d3、喹硫平-d8、阿立哌唑-d8和齐拉西酮-d8稳定同位素为内标,血清样品经过前处理后采用UPLCMS/MS对上清液进行分析。结果:空白血清对药物的检测无干扰,氯氮平、N-去甲基氯氮平、喹硫平、阿立哌唑及齐拉西酮在1. 00~1 000μg/L范围内线性良好,相关系数r> 0. 998 8;日内、日间精密度(RSD)均小于15%,回收率90%~110%;样品在室温12 h、4℃冰箱48 h、自动进样器24 h及反复冻融3次的情况下都能保持稳定。结论:本方法前处理操作简单,能够快速、准确、高通量地检测所选择的5种非典型抗精神病药物的血药浓度。
Objective: To establish a fast and precise method for simultaneously determining the five atypical antipsychotics clozapine,N-desmethyl clozapine,quetiapine,aripiprazole and ziprasidone in human serum by ultra performance liquid chromatography tandem mass spectrometry( UPLC-MS/MS).Methods: Clozapine-d3,quetiapine-d8,aripiprazole-d8 and ziprasidone-d8 were used as internal standards and the serum samples were analyzed by UPLC-MS/MS after pretreatment. Results: The detection result of the five drugs was not disturbed by blank matrix; the linearity of five drugs was well in the range of 1. 00 ~ 1 000 μg/L and the correlation coefficients were higher than 0. 998 8; the relative standard deviations( RSDs) of intra-and inter-day precision were lower than 15%; the average recoveries were between 90% to 110%. All the five drugs remained stability under the condition of room temperature for 12 hours,4 degrees centigrade in fridge for 48 hours,automatic sampler for 24 hours and after three freeze-thaw cycles. Conclusion: The pretreatment process is very simple and this method can meet the requirements of fast,accuracy and high throughput in clinical in monitoring this five atypical antipsychotics in clinical.

关键词(KeyWords): 超高效液相串联质谱;血药浓度;非典型抗精神病药物;血清;同位素内标
ultra-high performance liquid chromatography tandem mass spectrometry;blood drug concentration;atypical antipsychotics;serum;isotope internal standard

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作者(Author): 王玮;余淑珍;彭军;许洪涛;
WANG Wei;YU Shuzhen;PENG Jun;XU Hongtao;Department of Pharmacy,Jiangsu Integrated Traditional Chinese and Western Medicine Hospital;Hangzhou BIOZON Medical Institute Co.,Ltd;

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DOI: 10.19367/j.cnki.1000-2707.2018.12.012

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