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Screening and quantification of antipsychotic drugs in human brain tissue by liquid chromatography-tandem mass spectrometry: Application to postmortem diagnostics of forensic interest

机译:液相色谱-串联质谱法在人脑组织中抗精神病药物的筛选和定量:在法医事后诊断中的应用

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摘要

A quantitative LC-MS/MS method has been developed for the simultaneous determination of 17 antipsychotic drugs in human postmortem brain tissue. Sample preparation was performed using Hybrid Solid Phase Extraction-Precipitation technology for the removal of endogenous protein and phospholipid interferences. The chromatographic separation was performed for 16min on a C8 column, which used a gradient elution of formate ammonium and acetonitrile, and a flow rate gradient. Triple quadrupole mass spectrometry was employed to generate tandem mass spectrometric (MS/MS) data of the target analytes to select the ion m/z signals. Quantitation of the analytes was performed by operating in the dynamic multiple reaction monitoring (dMRM) mode using an electrospray ionization interface. Calibration curves prepared in the spiked brain tissue were linear in the range 20-8000ng/g (r 20.993) for all drugs (except olanzapine). Within- and between-day coefficients of variation were lower than 25% for all drugs at the LOQ. The LOQ in the matrix ranged between 2ng/g and 80ng/g. The method was successfully applied to the unequivocal identification and accurate quantification of antipsychotic drugs in human postmortem brain tissues: therefore, this method can be used in forensic investigations.
机译:已经开发了一种定量LC-MS / MS方法,用于同时测定人死后脑组织中的17种抗精神病药。使用杂化固相萃取沉淀技术进行样品制备,以去除内源性蛋白质和磷脂干扰。在C8色谱柱上进行色谱分离16分钟,该色谱柱使用甲酸铵和乙腈的梯度洗脱以及流速梯度进行。采用三重四极杆质谱法生成目标分析物的串联质谱(MS / MS)数据,以选择离子m / z信号。通过使用电喷雾电离界面以动态多反应监测(dMRM)模式进行操作,对分析物进行定量。对于所有药物(奥氮平除外),在加标的脑组织中制备的校准曲线在20-8000ng / g范围内呈线性(r 2> 0.993)。 LOQ下所有药物的日内和日间变异系数均低于25%。矩阵中的LOQ在2ng / g和80ng / g之间。该方法已成功应用于人死后脑组织中抗精神病药的明确鉴定和准确定量:因此,该方法可用于法医研究。

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