Pelander Anna, Ojanperä Ilkka, Laks Suvi, Rasanen Ilpo, Vuori Erkki
Department of Forensic Medicine, P.O. Box 40, and Department of Analytical Chemistry, P.O. Box 55, FIN-00014, University of Helsinki, Finland.
Anal Chem. 2003 Nov 1;75(21):5710-8. doi: 10.1021/ac030162o.
An analytical procedure was evaluated for the comprehensive toxicological screening of drugs, metabolites, and pesticides in 1-mL urine samples by TurboIon spray liquid chromatography/time-of-flight mass spectrometry (LC/TOFMS) in the positive ionization mode and continuous mass measurement. The substance database consisted of exact monoisotopic masses for 637 compounds, of which an LC retention time was available for 392. A macroprogram was refined for extracting the data into a legible report, utilizing metabolic patterns and preset identification criteria. These criteria included +/-30 ppm mass tolerance, a +/-0.2-min window for absolute retention time, if available, and a minimum area count of 500. The limit of detection, determined for 90 compounds, was <0.1 mg/L for 73% of the compounds studied and >1.0 mg/L for 6% of the compounds. For method comparisons, 50 successive autopsy urine samples were analyzed by this method, and the results confirmed by gas chromatography/mass spectrometry (GC/MS). Findings for parent drugs were consistent with both methods; in addition, LC/TOFMS regularly revealed apparently correct findings for metabolites not shown by GC/MS. Mean and median mass accuracy by LC/TOFMS was 7.6 and 5.4 ppm, respectively. The procedure proved well-suited for tentative identification without reference substances. The few false positives emphasized the fact that all three parameters, exact mass, retention time, and metabolite pattern, are required for unequivocal identification.
采用TurboIon喷雾液相色谱/飞行时间质谱法（LC/TOFMS）在正离子模式和连续质量测量条件下，对1 mL尿液样本中的药物、代谢物和农药进行综合毒理学筛查，对一种分析方法进行了评估。物质数据库包含637种化合物的精确单同位素质量，其中392种有LC保留时间。利用代谢模式和预设的识别标准，对一个宏程序进行了优化，以便将数据提取成一份清晰易读的报告。这些标准包括±30 ppm的质量容差、±0.2分钟的绝对保留时间窗口（如有）以及至少500的面积计数。对90种化合物测定的检测限，73%的研究化合物<0.1 mg/L，6%的化合物>1.0 mg/L。为了进行方法比较，用该方法分析了50份连续的尸检尿液样本，结果通过气相色谱/质谱法（GC/MS）得到证实。母体药物的检测结果在两种方法中是一致 的；此外，LC/TOFMS经常能揭示出GC/MS未显示的代谢物的明显正确结果。LC/TOFMS的平均和中位数质量准确度分别为7.6 ppm和5.4 ppm。该方法被证明非常适合在没有参考物质的情况下进行初步鉴定。少数假阳性结果强调了一个事实，即明确鉴定需要精确质量、保留时间和代谢物模式这三个参数。
