UPLC-MS/MS快速检测人血浆中7种苯二氮?类药物

【作者】 毕重文； 张佳成； 詹达强； 李正翔； 袁恒杰；

【机构】 天津医科大学总医院；

【摘要】 目的:建立并验证一种同时检测人血浆中7种常见BZDs药物的方法。方法:血浆样品经乙腈沉淀蛋白后,采用液相-串联质谱联用仪测定。色谱柱为BEH C18,以含0.01%甲酸乙腈溶液-含0.01%甲酸水溶液为流动相梯度洗脱,流速为0.4 ml/min,采用MRM多通道,ESI正离子模式监测。结果:劳拉西泮、硝西泮、阿普唑仑、咪达唑仑、三唑仑、氯硝西泮、地西泮浓度分别在62.5～2000(r=0.9998)、62.5～2000(r=0.9997)、31.25～1000(r=0.9999)、62.5～2000(r=0.9997)、6.25～200(r=1)、62.5～2000(r=0.9997)、625～20000(r=0.9968)ng/mL内线性关系良好;定量下限分别为7.8、3.9、1.9、3.9、3.1、3.9、19.5 ng/mL;日内和日间精密度均小于<14.75%;提取回收率均在74.55～96.72%之间;基质效应均在81.68%～97.20%内;血浆样品室温放置12 h、4°C放置24 h、反复冻融3次、-20°C放置1个月、提取处理后进样器(15°C)放置24 h稳定(相对误差均在±15%之内)。讨论:本方法检测速度快、专属性强、重复性好,已用于临床检测,可有效检测治疗及中毒浓度范围的7种药物。此外,本方法可有效评价血液净化的清除效率,对处于不同治疗阶段的中毒患者,均具有重要的临床指导意义。更多还原

【Abstract】 OBJECTIVE: To establish and validate a method for simultaneous detection of 7 common BZDs in human plasma.METHODS: The plasma samples were measured by liquid phase-tandem mass spectrometry after their proteins were precipitated by acetonitrile. The chromatographic column was BEH C18. Acetonitrile solution with 0.01% formic acid and water solution with0.01% formic acid were used as mobile phase to perform gradient elution. The flow rate was 0.4 mL/min. MRM and ESI positive ion mode were used for monitoring.RESULTS: The linear ranges of lorazepam, niazepam, alprazolam, midazolam, triazolam,clonazepam and diazepam were 62.5～2000(r=0.9998)、62.5～2000(r=0.9997)、31.25～1000(r=0.9999)、62.5～2000(r=0.9997)、6.25～200(r=1)、62.5～2000(r=0.9997)、625～20000(r=0.9968)ng/mL, respectively. The minimum quantitative limit was 7.8,3.9, 1.9, 3.9, 3.1, 3.9, and 19.5 ng/mL, respectively. The RSDs of inter-day and intra-day precision were both less than <14.75%. The extraction recovery rates were all between 74.55 and 96.72%. The matrix effects were all within 81.68%～97.20%.Plasma samples at room temperature for 12 h, at 4 ° C for 24 h, 3 times repeated freezing and thawing, at-20 °C for 1 months and extracted samples stored at 15 °C for 24 h were all stabile(relative errors are within 15%).CONCLUSIONS: This method has been successfully used for clinical detection and 7 drugs can be effectively detected in the range of treatment and toxic concentration.In addition, this method can effectively evaluate the removal efficiency of blood purification, and has important clinical guiding significance for poisoning patients at different treatment stages.更多还原