Chang T L, Chen K W, Lee Y D, Fan K
Department of Pathology, National Cheng Kung University Hospital, Tainan, Taiwan, ROC.
J Clin Lab Anal. 1999;13(3):106-11. doi: 10.1002/(SICI)1098-2825(1999)13:3<106::AID-JCLA3>3.0.CO;2-L.
Emergency toxicology or drug screening in clinical settings requires rapid qualitative and quantitative analysis with acceptable levels of sensitivity and specificity. The aim of this study was to comparatively evaluate the performance of the multi-column HPLC-based REMEDi drug profiling system (Bio-Rad), the aca analyzer (Du Pont), and the bench standard conventional HPLC method in the identification of 12 clinically important benzodiazepines. In this study, the presence of benzodiazepines in 133 patients' serum samples were qualitatively and comparatively analyzed by these three procedures. Among these methods, 120 of 133 samples were identified as benzodiazepine-positive by conventional HPLC (90%); 127 by aca analyzer (95%); and 84 by REMEDi (63%). Detection sensitivity of REMEDi for most of the benzodiazepines was found satisfactory when concentrations were greater than 1.0 microg/mL. When benzodiazepine concentrations were in the ranges of 0.3-1.0 microg/mL, detection sensitivity became varied among the benzodiazepine family of drugs by REMEDi method. REMEDi procedure should not be considered as the method of choice for detection of benzodiazepines if expected concentration levels are below 0.3 microg/mL, with the exception of bromazepam. Conventional HPLC displayed the highest sensitivity and specificity for the detection of benzodiazepines. In our studies, 36 REMEDi-negative samples were positive by HPLC, although in 16 of the 36 REMEDi negative samples (13.3%), the presence of benzodiazepines was detected but only listed as candidates without positive identification of the individual compounds by REMEDi. In our series, however, there were no false positives by the REMEDi method whereas aca procedure showed 13 false positive results (9%) and 6 cases of false negative (4%). Our data indicate that the REMEDi procedure can be used on serum samples for rapid qualitative screening of clinically important high levels of benzodiazepines with high specificity. However, due to the relatively low sensitivity of REMEDi in samples with low benzodiazepine levels and relatively low specificity by aca, all samples should be further confirmed by conventional HPLC procedure.
临床环境中的急诊毒理学或药物筛查需要进行快速的定性和定量分析，且灵敏度和特异性要达到可接受的水平。本研究的目的是比较评估基于多柱高效液相色谱法的REMEDi药物分析系统（伯乐公司）、aca分析仪（杜邦公司）以及作为基准标准的传统高效液相色谱法在鉴定12种临床重要苯二氮䓬类药物方面的性能。在本研究中，采用这三种方法对133例患者血清样本中的苯二氮䓬类药物进行了定性和比较分析。在这些方法中，133份样本中有120份通过传统高效液相色谱法鉴定为苯二氮䓬类药物阳性（90%）；127份通过aca分析仪鉴定为阳性（95%）；84份通过REMEDi鉴定为阳性（63%）。当浓度大于1.0微克/毫升时，发现REMEDi对大多数苯二氮䓬类药物的检测灵敏度令人满意。当苯二氮䓬类药物浓度在0.3 - 1.0微克/毫升范围内时，REMEDi方法对不同苯二氮䓬类药物的检测灵敏度有所不同。如果预期浓度水平低于0.3微克/毫升，除溴西泮外，REMEDi方法不应被视为检测苯二氮䓬类药物的首选方法。传统高效液相色谱法在检测苯二氮䓬类药物方面表现出最高的灵敏度和特异性。在我们的研究中，36份REMEDi阴性样本通过高效液相色谱法检测为阳性，尽管在这36份REMEDi阴性样本中有16份（13.3%）检测到了苯二氮䓬类药物的存在，但REMEDi仅将其列为候选药物，未对单个化合物进行阳性鉴定。然而，在我们的系列研究中，REMEDi方法没有假阳性结果，而aca方法出现了13例假阳性结果（9%）和6例假阴性结果（4%）。我们的数据表明，REMEDi方法可用于血清样本，以高特异性快速定性筛查临床重要的高浓度苯二氮䓬类药物。然而，由于REMEDi在低苯二氮䓬类药物水平样本中的灵敏度相对较低，且aca的特异性相对较低，所有样本都应通过传统高效液相色谱法进一步确认。
