Shin Miok, Ji Dajeong, Kang Soyoung, Yang Wonkyung, Choi Hwakyung, Lee Sooyeun
College of Pharmacy, Keimyung University, 1095 Dalgubeoldaero, Dalseo-gu, Daegu, 704-701, Republic of Korea.
Arch Pharm Res. 2014 Jun;37(6):760-72. doi: 10.1007/s12272-013-0225-0. Epub 2013 Aug 6.
A recent trend in urine drug testing in forensic and clinical toxicology has been the simultaneous determination of different chemical groups of target drugs, which are selected based on their local popularity. Rapid multiple drug analysis, made possible by the use of liquid chromatography-tandem mass spectrometry (LC/MS/MS), has become more widely used, especially in workplace drug testing. Therefore, in the present study, a method for simultaneously analyzing 35 drugs of abuse and relevant metabolites that are most prevalent in Korea, using LC/MS/MS with polarity switching electrospray ionization, was developed and validated. The drugs and metabolites in urine were extracted by using mixed mode strong cation exchange polymeric solid phase extraction cartridges after enzymatic hydrolysis and were then injected into the LC/MS/MS system. The validation results for selectivity, linearity, intra- and inter-assay precision and accuracy for this method were satisfactory, while the results for matrix effects and recovery showed significant variance among the urine samples from different sources. The limits of detection ranged from 0.1 to 10 ng/ml and the limits of quantification were from 1 to 10 ng/ml. To reduce the matrix effects in authentic samples, two different quantitative approaches were compared: quantification using calibration standards prepared by the drug-free pooled urine matrix and quantification using the standard addition. Of these, the latter method was found to be the most suitable. The method developed in this study will be very useful for forensic and clinical toxicology laboratories to adopt for monitoring the inappropriate use of controlled drugs.
法医和临床毒理学中尿液药物检测的一个最新趋势是同时测定不同化学类别的目标药物,这些药物是根据当地的流行程度来选择的。液相色谱-串联质谱法(LC/MS/MS)实现的快速多药物分析已得到更广泛的应用,尤其是在工作场所药物检测中。因此,在本研究中,开发并验证了一种使用带极性切换电喷雾电离的LC/MS/MS同时分析韩国最常见的35种滥用药物及其相关代谢物的方法。尿液中的药物和代谢物在酶水解后使用混合模式强阳离子交换聚合物固相萃取柱进行萃取,然后注入LC/MS/MS系统。该方法在选择性、线性、批内和批间精密度及准确度方面的验证结果令人满意,而基质效应和回收率的结果在不同来源的尿液样本中显示出显著差异。检测限范围为0.1至10 ng/ml,定量限为1至10 ng/ml。为了减少实际样品中的基质效应,比较了两种不同的定量方法:使用无药物混合尿液基质制备的校准标准进行定量和标准加入法进行定量。其中,后一种方法被认为是最合适的。本研究中开发的方法对于法医和临床毒理学实验室监测管制药物的不当使用将非常有用。