液相色谱-四极杆/飞行时间质谱法快速筛查测定药物中芬太尼类物质

基于液相色谱-四极杆/飞行时间质谱(LC-QTOF-MS)建立了药物中27种新型毒品芬太尼类物质(芬太尼及其类似物)的同时快速筛查、确证和定量分析方法。样品经5 mL 75%(v/v)乙腈水溶液和5 mL乙腈提取,HLB固相萃取柱净化,电喷雾电离,正离子扫描,TOF-MS和信息依赖性采集(IDA)-MS/MS采集模式检测,外标法定量;建立一级精确质量数据库、保留时间和二级质谱库,实现了固体压片、粉末、液体药物及透皮贴剂中27种芬太尼类物质的快速筛查和确证。在5.00~100μg/L范围内,27种目标化合物的线性关系良好(r2>0.99)。27种化合物的定量限均为10.0μg/kg。在维生素C压片、头痛粉、止咳水、透皮贴剂样品中3个添加水平的平均回收率范围分别82.9%~106%、84.8%~106%、86.9%~109%和83.1%~106%,相对标准偏差(RSD)为0.38%~8.71%(n=6)。本方法操作简便,耗时短,灵敏度高,稳定性好,适用于液体和固体药物中芬太尼类物质的筛查检测及定量分析,可显著降低检测成本,具有实际应用价值。

Rapid screening and determination of fentanyl and its analogues in drugs by liquid chromatography- quadrupole time-of-flight mass spectrometry

A method based on liquid chromatography coupled with high-resolution quadrupole time-of-flight mass spectrometry (LC-QTOF-MS) was developed for the simultaneous screening and determination of fentanyl and its 26 analogs in liquid and solid powder drugs. The established method involves successive extraction by 5 mL 75% (v/v) acetonitrile aqueous solution and 5 mL acetonitrile, followed by clean-up using the hydrophilic lipophilic balance (HLB) solid-phase extraction method. Detection was achieved by electrospray ionization (ESI) in the positive mode, TOF-MS, and information-dependent acquisition (IDA)-MS/MS acquisition; the external standard method was adopted for quantification. Two databases of accurate mass and fragment ions were created. The standard matrix-matched calibration curves of the 27 target compounds were linear in the range of 5.00-100 μg/L, with the correlation coefficients (r²)>0. 99. The limits of quantification for the 27 target compounds were 10.0 μg/kg. The recoveries for all the target compounds in vitamin C tablet, headache powder, cough syrup, and transdermal patch samples were in the ranges of 82.9%-106%, 84.8%-106%, 86.9%-109%, and 83.1%-106%, respectively, with relative standard deviations ranging from 0.38% to 8.71% (n=6). The results demonstrated that the developed method is rapid and sensitive for the simultaneous monitoring and determination of fentanyl and 26 its analogs in liquid and solid powder drugs.