人血浆中7种影响驾驶安全的药物血药浓度的UPLC-MS/MS法测定  

Determination of Blood Concentrations of Seven Chemicals Affecting Driving Safety by UPLC-MS/MS

作　　者：王伟[1] 陈振玲[1] 祁妍敏[1] 于红燕[1] 

机构地区：[1]中国民用航空局民用航空医学中心(民航总医院),北京100123

出　　处：《中国医药工业杂志》2017年第8期1176-1181,共6页Chinese Journal of Pharmaceuticals

基　　金：民航局科技项目(MHRD201042);国家自然基金(U1333132);中国民用航空局重大科技专项(MHRD20140101)

摘　　要：本研究建立了超高效液相色谱-串联质谱法测定人血浆中的7种影响驾驶安全的药物——赛庚啶、西替利嗪、氯苯那敏、艾司唑仑、劳拉西泮、氯硝西泮和地西泮,这些药物是中药制剂和保健品中易违禁添加的化学成分。以奥沙西泮为内标,使用Acquity UPLC HSS C_(18)色谱柱,流动相为0.01%甲酸水溶液∶0.01%甲酸甲醇溶液,线性梯度洗脱。质谱采用电喷雾离子源,多反应监测模式,正离子分段扫描分析。结果表明,赛庚啶、西替利嗪、氯苯那敏、艾司唑仑、劳拉西泮、氯硝西泮和地西泮分别在3.75~3.00×10~3、2.00~2.00×10~3、0.25~1.00×10~2、2.04~2.04×10~3、2.08~2.08×10~3、2.08~2.08×10~3和2.65~1.06×10~3 ng/ml范围内线性关系良好;最低检测限(LLOD)分别为0.38、0.50、0.10、0.51、0.52、0.52和0.05 ng/ml。日内、日间RSD均小于15%;提取回收率均大于70%,RSD<15%。内标的提取率为(80.67±4.29)%(RSD=5.32%)。该方法操作简便、灵敏度高、专属性强,可用于上述7种化合物血药浓度的测定。A UPLC-MS/MS method was established for the determination of seven drugs affecting driving safety, including cyproheptadine, cetirizine, chlortrimeton, estazolam, lorazepam, clonazepam and diazepam, which were often added illegally into traditional Chinese medicine and health food. Oxazepam was used as the internal standard. An Acquity UPLC HSS C18 column was used, with the mobile phase of0.01% formic acid aqueous solution ： 0.01% formic acid methanol solution for gradient elution. Multiple reaction monitoring （MRM） mode was performed combined with the positive ion mode for quantification in four sections. Results showed that the calibration curves of the above seven compounds were linear in the concentration ranges of 3.75--3.00× 10^3, 2.00--2.00×10^3, 0.25--1.00×10^2, 2.04--2.04× 10^3, 2.08--2.08×10^3, 2.08--2.08×10^3 and 2.65--1.06×10^3 ng/ml, respectively. Their lowest limit of detection （LLOD） were 0.38, 0.50, 0.10, 0.51, 0.52, 0.52 and 0.05 ng/ml, respectively. The inter- and intra-day RSDs were less than 15%. Their relative recoveries were more than 70 %, and the RSDs were less than 15 %. The relative recovery of the internal standard was （80.67＋4.29） %, with RSD of 5.32%. The method established in our work was accurate, sensitive and specific, which was suitable for the simultaneous determination of the above seven chemicals in human plasma.

关 键 词：苯二氮[艹卓]类药物 抗组胺类药物 血药浓度 超高效液相色谱-质谱法 

分 类 号：O657.72[理学—分析化学]