Van Nimmen Nadine F J, Poels Katrien L C, Veulemans Hendrik A F
Department of Occupational, Katholieke Universiteit Leuven, Environmental and Insurance Medicine, Laboratory for Occupational Hygiene and Toxicology, Kapucijnenvoer 35, 6th floor, B-3000 Leuven, Belgium.
J Chromatogr B Analyt Technol Biomed Life Sci. 2004 May 25;804(2):375-87. doi: 10.1016/j.jchromb.2004.01.044.
Highly sensitive and specific analytical GC-MS procedures were developed and comprehensively validated for the determination of the opioid narcotics fentanyl, sufentanil and alfentanil and their major nor-metabolites in urine of potentially exposed opioid production workers. A simple, one step extraction protocol was developed using commercially available solid phase extraction (SPE) columns to recover all analytes from urine. The secondary amine functionalities of the nor-metabolites were derivatized to form stable, pentafluorobenzamide (PFBA)-derivatives with good chromatographic properties. Using the penta-deuterated analogues as internal standards, a limit-of-detection (LOD) of 2.5 pg fentanyl/ml, 2.5 pg sufentanil/ml and 7.5 pg alfentanil/ml urine was achieved. For the opioid metabolites the LODs were found to be <50 pg/ml urine. The developed analytical procedures show excellent intra-assay accuracy, particularly considering the ultra low levels of the analytes, with relative errors generally below 10%. Overall, an excellent reproducibility was observed with coefficients of variation below 10% at all spike levels for all opioid parent compounds and their metabolites, except for low norfentanyl concentrations. Upon storage at -30 degrees C urine samples were found to be stable for at least 2 months as no significant losses of either compound were observed. The developed analytical procedures have been successfully applied in a biological monitoring survey of fentanyl exposed production workers.
针对潜在接触阿片类药物生产工人尿液中的阿片类麻醉剂芬太尼、舒芬太尼和阿芬太尼及其主要去甲代谢物的测定，开发了高灵敏度和特异性的分析气相色谱 - 质谱（GC-MS）方法，并进行了全面验证。使用市售的固相萃取（SPE）柱开发了一种简单的一步萃取方案，用于从尿液中回收所有分析物。去甲代谢物的仲胺官能团被衍生化，以形成具有良好色谱性能的稳定的五氟苯甲酰胺（PFBA）衍生物。以五氘代类似物作为内标，尿液中芬太尼的检测限（LOD）为2.5 pg/ml，舒芬太尼为2.5 pg/ml，阿芬太尼为7.5 pg/ml。对于阿片类代谢物，发现尿液中的检测限<50 pg/ml。所开发的分析方法显示出出色的批内准确性，特别是考虑到分析物的超低水平，相对误差通常低于10%。总体而言，除了低浓度的去甲芬太尼外，所有阿片类母体化合物及其代谢物在所有加标水平下的变异系数均低于10%，具有出色的重现性。在-30℃储存时，尿液样本被发现至少稳定2个月，因为未观察到任何一种化合物有明显损失。所开发的分析方法已成功应用于芬太尼暴露生产工人的生物监测调查。
