摘要
目的建立一个快速、灵敏和专属性好的液质联用方法,来检测等效性试验中抗肿瘤药替莫唑胺的血药浓度。方法将血浆样本用甲醇和乙腈(1∶2,含1%甲酸)作为沉淀剂进行蛋白沉淀后,涡旋离心,取上清100μL进样分析,使用Phenomene C_(18) 100A柱(3.0 mm×50 mm),采用等度洗脱,流动相为0.1%甲酸水溶液-0.1%甲酸甲醇溶液(9∶1),流速为0.3 m L·min^(-1),检测器采用API5500 QTrap质谱检测器,正离子模式,MRM扫描方式,待测物和内标的离子对分别是是m/z 195.1→m/z 138.0(替莫唑胺)和m/z 198.1→m/z 138.0(替莫唑胺-d3,内标)。结果该方法的标准曲线范围是0.05~30μg·m L^(-1)(r>0.9973),最低定量下限为0.05μg·m L^(-1)。血样日内、日间RSD为1.06%~7.13%和1.80%~5.19%,批内批间准确度分别为:91.02%~109.33%和95.14%~101.22%,样本回收率、基质效应和专属性都满足检测要求。结论该方法快速、灵敏和专属性好,成功用于替莫唑胺等效性实验的血浆浓度检测。
Objective To develop a rapid,sensitive and specific analytical method based on liquid chromatographytandem mass spectrometry（ LC-MS/MS） for the determination of temozolomide concentration in human plasma in equivalence trial clinical trial. Methods After protein sediment by methanol and acetonitrile（ 1 ∶ 2,0. 1% formic acid）,the analyte and internal standard were separated on a Kinetex C（18） column（ 3. 0 mm × 50 mm） using a isocratic elution consisting of 0. 1% formic acid water solution 0. 1% formic acid and methanol（ 9∶ 1） as the mobile phase at a flow rate of 0. 3 m L · min^-1. The detection was performed using an API 5500 QTrap mass spectrometer in the positive electrospray ionization（ ESI） mode. The multiple reaction monitoring（ MRM） transitions were m/z 195. 1→m/z 138. 0 for the analyte and m/z 198. 1→m/z138. 0 for temozolomide-d3. Results The calibration curve exhibited a linear dynamic range of 0. 05-30 μg·m L^-1（ r 〉0. 997 3）. The intra-and inter-day precisions（ relative standard deviation, RSD） were1. 06%-7. 13% and 1. 80%-5. 19%. The intraand interday precisions were 91. 02%-109. 33% and 95. 14%-101. 22%. The recoveries and matrix effects were satisfactory in all the biological matrices examined.Conclusion This method was successfully used for the determination of temozolomide concentration in human plasma in equivalence trial.
作者
陈刚
王进
王泽娟
孔小轶
刘晓娜
刘晨
刘英
漆璐
周保利
李文斌
王兴河
CHEN Gang1, WANGJin1, WANG Ze - juan1, KONG Xiao - yi2, LIU Xiao- na1, LIU Chen1, LIU Ying 1, QI LU1, ZHOU Bao- li3, LI Wen - bin4 , WANG Xing - he1(1. Phase I Clinical Trial Center; 3. Administrative Office; 4. Department of Neuro - Oncology, Beijing Shifitan Hospital, Capital Medical University, Beijing 100038, China ; 2 College of Pharmacy, Jinan University, Guangzhou 510632, Chin)
出处
《中国临床药理学杂志》
CAS
CSCD
北大核心
2018年第9期1111-1114,共4页
The Chinese Journal of Clinical Pharmacology
基金
北京市科委课题基金资助项目(Z111100059411059)
关键词
液质联用
血浆浓度
替莫唑胺
liquid chromatographytandem mass spectrometry
plasma concentration
temozolomide
