Abstract: Objective An online solid phase extraction-ultra high performance liquid chromatography tandem mass spectrometry （SPE-UPLC-MS/MS） method for the simultaneous determination of 21 illicit drugs and their metabolites including fluoroketamine in wasterwater was established. Methods The pH value of a sewage sample was adjusted to 8 by adding 10 % ammonia solution and 4 mol/L ammonium acetate solution. Then an appropriate amount of isotopic internal standard was added to the sewage sample. After filtration, the sample was loaded on an HLB Direct Connect HP SPE column （2.1 mm×30 mm, 20 μm） to allow the online SPE. The targets were eluted in reverse phase and loaded on an ACQUITY UPLC HSS T₃ column（100 mm×2.1 mm, 1.8 μm） for liquid chromatography separation. The gradient elution was carried out using 0.1% formic acid aqueous solution and 0.1 % （volume fraction） formic acid-acetonitrile solution as the mobile phase. The electrospray ion source was set in the positive ion mode. Multiple reaction monitoring （MRM） mode was used for quantitative analysis. Results Except for morphine and O6-monoacetylmorphine whose linear ranges were 2-200 ng/L, the linear ranges of the other 19 targets were 1-200 ng/L, with the correlation coefficient not less than 0.998 5. The accuracy ranged from 81.73 % to 109.47 %, and the intra-day and inter-day precision were both less than 13.87 %. Compared with off-line SPE methods, the online SPE method eliminated complex pre-treatment procedures in SPE and concentration process. It not only improves the efficiency of sample analysis, but also reduces potential pollution in pre-treatment. Conclusion The established method has good selectivity, accuracy and repeatability. It has been applied in the determination of fluoroketamine and other illicit drugs as well as their metabolites in wasterwater samples in different regions of China.

Key words: online solid phase extraction, UPLC-MS/MS, sewage, Fluoroketamine, drugs

摘要： 目的 建立一种基于在线固相萃取-超高效液相色谱-串联质谱法（SPE-UPLC-MS/MS）同时检测污水中氟胺酮等21种毒品及其代谢物的方法。方法 分别添加10 %（体积分数）氨水溶液和4 mol/L乙酸铵溶液将污水样品pH值调节至8，在污水中添加适量同位素内标，过滤后将样品加载至在线固相萃取系统，先用Oasis HLB Direct Connect HP固相萃取柱（2.1 mm × 30 mm，20 μm）对目标物进行在线固相萃取，再将目标物反相洗脱并加载至ACQUITY UPLC HSS T3色谱柱（100 mm × 2.1 mm，1.8 μm）中，以0.1 %甲酸水溶液和0.1 %甲酸-乙腈溶液作为流动相进行梯度洗脱。采用电喷雾离子源正离子、多反应监测模式（MRM）进行定量分析。结果 除了吗啡、O⁶-单乙酰吗啡的线性范围为 2~200 ng/L外，其他目标物的定量线性范围为1~200 ng/L，线性关系良好（相关系数r≥0.998 5），准确度为81.73 %~109.47 %，日内、日间精密度均小于13.87 %。与离线固相萃取法相比，在线固相萃取法省去复杂的固相萃取和浓缩等前处理过程，在提高样品分析效率的同时，减少了前处理过程带来污染的可能性。结论 该方法具有良好的选择性、准确性和重复性，已用于我国各地污水中氟胺酮等毒品及其代谢物的测定。

关键词: 在线固相萃取, 超高效液相色谱-串联质谱法, 污水, 氟胺酮, 毒品