Thevis Mario, Geyer Hans, Bahr Daniel, Schänzer Wilhelm
Institute of Biochemistry, German Sport University Cologne, Carl-Diem Weg 6, 50933 Cologne, Germany.
Eur J Mass Spectrom (Chichester). 2005;11(4):419-27. doi: 10.1255/ejms.761.
Since January 2005, the list of prohibited substances established by the World Anti-Doping Agency prohibits the opioid agent fentanyl as well as its related drugs in professional and amateur sports. Fast, reliable and robust analytical assays are required that allow the sensitive determination of these compounds or respective metabolites in human urine, and liquid chromatography interfaced to mass spectrometry has proven to be a suitable and powerful tool for drug testing for several years. A screening and confirmation method was developed that enables the identification of fentanyl, alfentanil, remifentanil and sufentanil as well as their N-dealkylated or de-esterified metabolites utilizing solid-phase extraction of a 2 mL urine aliquot followed by LC-electrospray-MS/MS analysis. The procedure was validated in terms of recovery (95.8-104.9%), lower limit of detection (0.5 ng mL-1), specificity and interday precision (3.9-19.8%) for the four opioid drugs and the metabolic product norfentanyl. In addition, the mass spectrometric behavior of fentanyl after electrospray ionization and collision-induced dissociation was studied by synthesis and analysis of structurally related compounds, and dissociation pathways were proposed allowing the characterization of target analytes and corresponding metabolites.
自2005年1月起，世界反兴奋剂机构制定的禁用物质清单禁止在职业和业余体育赛事中使用阿片类药物芬太尼及其相关药物。因此，需要快速、可靠且稳健的分析方法，以便能够灵敏地测定人尿中的这些化合物或其相应代谢物，而液相色谱与质谱联用已被证明多年来一直是药物检测的合适且强大的工具。本文开发了一种筛查和确证方法，该方法通过对2 mL尿样进行固相萃取，然后进行液相色谱-电喷雾-串联质谱分析，能够鉴定芬太尼、阿芬太尼、瑞芬太尼和舒芬太尼及其N-脱烷基化或脱酯化代谢物。该方法在回收率（95.8-104.9%）、检测下限（0.5 ng mL-1）、特异性和日间精密度（3.9-19.8%）方面针对四种阿片类药物及其代谢产物去甲芬太尼进行了验证。此外，通过合成和分析结构相关化合物，研究了芬太尼在电喷雾电离和碰撞诱导解离后的质谱行为，并提出了解离途径，以便对目标分析物及其相应代谢物进行表征。
