Sauvage François-Ludovic, Saint-Marcoux Franck, Duretz Bénédicte, Deporte Didier, Lachatre Gérard, Marquet Pierre
Department of Pharmacology-Toxicology, University Hospital, Limoges, France.
Clin Chem. 2006 Sep;52(9):1735-42. doi: 10.1373/clinchem.2006.067116. Epub 2006 Jul 20.
In clinical and forensic toxicology, general unknown screening is used to detect and identify exogenous compounds. In this study, we aimed to develop a comprehensive general unknown screening method based on liquid chromatography coupled with a hybrid triple-quadrupole linear ion trap mass spectrometer.
After solid-phase extraction, separation was performed using gradient reversed-phase chromatography. The mass spectrometer was operated in the information-dependent acquisition mode, switching between a survey scan acquired in the Enhanced Mass Spectrometry mode with dynamic subtraction of background noise and a dependent scan obtained in the enhanced product ion scan mode. The complete cycle time was 1.36 s. A library of 1000 enhanced product ion-tandem mass spectrometry spectra in positive mode and 250 in negative mode, generated using 3 alternated collision tensions during each scan, was created by injecting pure solutions of drugs and toxic compounds.
Comparison with HPLC-diode array detection and gas chromatography-mass spectrometry for the analysis of 36 clinical samples showed that linear ion trap tandem mass spectrometry could identify most of the compounds (94% of the total). Some compounds were detected only by 1 of the other 2 techniques. Specific clinical cases highlighted the advantages and limitations of the method.
A unique combination of new operating modes provided by hybrid triple-quadrupole linear ion trap mass spectrometers and new software features allowed development of a comprehensive and efficient method for the general unknown screening of drugs and toxic compounds in blood or urine.
在临床和法医毒理学中，一般未知物筛查用于检测和鉴定外源性化合物。在本研究中，我们旨在开发一种基于液相色谱与混合三重四极杆线性离子阱质谱联用的综合一般未知物筛查方法。
经过固相萃取后，采用梯度反相色谱进行分离。质谱仪以信息依赖采集模式运行，在增强质谱模式下采集的全扫描（动态扣除背景噪声）和增强产物离子扫描模式下获得的依赖扫描之间切换。完整的循环时间为1.36秒。通过注入药物和有毒化合物的纯溶液，创建了一个包含1000个正模式增强产物离子串联质谱图和250个负模式增强产物离子串联质谱图的库，每次扫描使用3种交替的碰撞能量。
与高效液相色谱 - 二极管阵列检测和气相色谱 - 质谱联用对36份临床样本的分析结果相比，线性离子阱串联质谱能够鉴定出大多数化合物（占总数的94%）。有些化合物仅能被其他两种技术中的一种检测到。具体临床案例突出了该方法的优缺点。
混合三重四极杆线性离子阱质谱仪提供的新操作模式与新软件功能的独特组合，使得开发出一种用于血液或尿液中药物和有毒化合物一般未知物筛查的全面且高效的方法成为可能。
