Development and validation of a highly sensitive gas chromatographic-mass spectrometric screening method for the simultaneous determination of nanogram levels of fentanyl, sufentanil and alfentanil in air and surface contamination wipes.
Development and validation of a highly sensitive gas chromatographic-mass spectrometric screening method for the simultaneous determination of nanogram levels of fentanyl, sufentanil and alfentanil in air and surface contamination wipes.
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DOI：
10.1016/j.chroma.2004.02.074
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发表时间：
2004-05
期刊：
影响因子：
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通讯作者：
N. F. J. Van Nimmen;H. Veulemans
中科院分区：
文献类型：
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作者：
N. F. J. Van Nimmen;H. Veulemans
建立了一种高灵敏度的气相色谱-质谱（GC-MS）分析方法，用于测定工业卫生个人空气样品和表面污染湿巾中阿片类麻醉品芬太尼、阿芬太尼和舒芬太尼。样品制备包括用甲醇一步提取样品，用一定量的阿片类麻醉品的五氘化类似物作为内标强化。采用选择性离子监测（SIM）的气相色谱-质谱分析方法具有很高的选择性。在全轮班960l空气样本的基础上，提取的擦拭物和空气样本的水平呈线性关系，至少对应于其表面污染限值（SCL）的0.1-2倍，相应地对应于其时间加权平均职业暴露限值（OEL-TWA）的0.1-2倍。对加标空气样品和表面湿巾的提取回收率进行了测定，并发现在整个研究范围内，两种取样介质的提取回收率都是定量的。空气采样方法的检出限（LOD）被确定为芬太尼和舒芬太尼为0.4ng /个样品，阿芬太尼为1.6ng /个样品，对应于全班次空气样品（960l）的单个OEL不到1%。芬太尼、舒芬太尼和阿芬太尼的定量限（LOQ）分别为1.4、1.2和5.0ng /过滤器。擦拭取样法芬太尼和舒芬太尼的lod分别为4ng /次，阿芬太尼的loq分别为14ng /次，12ng /次，50ng /次。空气采样和擦拭采样方法的分析内测定精度（定义为6个重复加标介质分析结果的变异系数）分别低于10%和5%，适用于所有阿片类药物的所有加标水平。以相对误差表示的准确度被确定为低于10%，除了阿芬太尼在最低峰水平（−13.1%）。研究了模拟空气取样过程中阿片类药物的稳定性。芬太尼和舒芬太尼在所有峰值水平上均有定量回收率，而阿芬太尼的回收率为60.3%至85.4%。当加标空气样本在室温和- 15℃下保存时，芬太尼和舒芬太尼在7天和14天后定量恢复。对于阿芬太尼，在储存7天后似乎有轻微的损失，14天后更明显。加标湿巾的环境储存似乎导致所有阿片类药物的显著损失，回收率为37.7-88.3%。类似的湿巾在- 15°C下储存时，回收率显著提高，范围从77.3到88.3%。所开发的分析和取样程序最近已应用于一个探索性的实地研究，本文介绍了表面污染擦拭取样的结果。据我们所知，这是第一项针对评估强效阿片类麻醉品外部职业暴露的分析程序的开发和验证的研究。
A highly sensitive gas chromatographic–mass spectrometric (GC–MS) analytical method for the determination of the opioid narcotics fentanyl, alfentanil, and sufentanil in industrial hygiene personal air samples and surface contamination wipes was developed and comprehensively validated. Sample preparation involved a single step extraction of the samples with methanol, fortified with a fixed amount of the penta-deuterated analogues of the opioid narcotics as internal standard. The GC–MS analytical procedure using selected ion monitoring (SIM) was shown to be highly selective. Linearity was shown for levels of extracted wipe and air samples corresponding to at least 0.1–2 times their surface contamination limit (SCL) and accordingly to 0.1–2 times their time weighted average occupational exposure limit (OEL-TWA) based on a full shift 960l air sample. Extraction recoveries were determined for spiked air samples and surface wipes and were found to be quantitative for both sampling media in the entire range studied. The air sampling method’s limit of detection (LOD) was determined to be 0.4ng per sample for fentanyl and sufentanil and 1.6ng per sample for alfentanil, corresponding to less than 1% of their individual OEL for a full shift air sample (960l). The limit of quantification (LOQ) was found to be 1.4, 1.2, and 5.0ng per filter for fentanyl, sufentanil, and alfentanil, respectively. The wipe sampling method had LODs of 4ng per wipe for fentanyl and sufentanil and 16ng per wipe for alfentanil and LOQs of respectively, 14, 12, and 50ng per wipe. The analytical intra-assay precision of the air sampling and wipe sampling method, defined as the coefficient of variation on the analytical result of six replicate spiked media was below 10 and 5%, respectively, for all opioids at all spike levels. Accuracy expressed as relative error was determined to be below 10%, except for alfentanil at the lowest spike level (−13.1%). The stability of the opioids during simulated air sampling was investigated. For fentanyl and sufentanil a quantitative recovery was observed at all spike levels, while for alfentanil recoveries ranged from 60.3 to 85.4%. When spiked air samples were stored at ambient temperature and at −15°C quantitative recovery was found for fentanyl and sufentanil after 7 and 14 days. For alfentanil a slight loss seemed to occur upon storage during 7 days, being more explicit after 14 days. Ambient storage of spiked wipes seemed to lead to significant losses of all opioids studied, yielding recoveries of 37.7–88.3%. Upon storage of similar wipes at −15°C a significantly higher recovery was found ranging from 77.3 to 88.3%. The developed analytical and sampling procedures have been recently applied in an explorative field study of which the results of surface contamination wipe sampling are presented in this paper. To our knowledge, this is the first study addressing the development and validation of analytical procedures for the assessment of external occupational exposure to potent opioid narcotics.