目的 建立了UPLC-MS/MS法测定半枝莲中印美定、石松胺、印美定氮氧化物和石松胺氮氧化物等4个吡咯里西啶生物碱的含量，并根据测定结果进行初步的风险评估。方法 采用ACQUITY UPLC HSS T3色谱柱（100 mm×2.1 mm，1.8 μm），以含0.05%甲酸和2.5 mmol/L甲酸铵的水溶液（A）及含0.05%甲酸和2.5 mmol/L甲酸铵的乙腈溶液（B）为流动相，梯度洗脱；电喷雾离子源，正离子多反应模式监测，外标法测定。采用暴露限值（MOE）法进行风险评估。结果 印美定、石松胺、印美定氮氧化物和石松胺氮氧化物质量浓度在0.974～97.400、0.992～99.200、1.024～102.400和1.012～ 101.200 ng/mL与峰面积呈现良好的线性关系（r>0.999）；平均加样回收率分别为88.7%、93.2%、94.8%、85.4%，RSD分别为4.1%、3.6%、4.4%、3.9%。6批半枝莲样品中印美定、石松胺、印美定氮氧化物和石松胺氮氧化物的含量范围分别为 0.18～0.66、0.11～0.42、0.78～2.21、0.19～0.97 μg/g，MOE值为3 134～6 461。结论 所建立的方法可同时测定半枝莲中4个主要吡咯里西啶生物碱含量；初步风险评估显示，该药材存在一定的用药安全风险。

Objective To establish a method for the simultaneous determination of four pyrrolizidine alkaloids (imtermedine, lycopsamine, imtermedine N-oxide, and lycopsamine N-oxide) in Scutellariae Barbatae Herba by UPLC-MS/MS. And to carry out preliminary risk assessment according to the research results. Methods The assay was performed on a ACQUITY UPLC HSS T3 column (100 mm×2.1 mm, 1.8 μm) and the sample was eluted with a gradient mobile phase consisted of 0.05% formic acid and 2.5 mmol/L ammonium formate in water (A)-0.05% formic acid and 2.5 mmol/L ammonium formate in acetonitrile (B). The MS system was operated by using electrospray ionization (ESI) in the positive ion mode, and the scan mode was in multiple reactions monitoring(MRM) mode. External standard method was used in the experiment. The risk assessment was carried out by margin of exposure (MOE) method. Results The linear ranges of imtermedine, lycopsamine, imtermedine N-oxide, and lycopsamine N-oxide were 0.974—97.4, 0.992—99.2, 1.024—102.4 and 1.012—101.2 ng/mL, respectively (r>0.999). The average recoveries were 88.7%, 93.2%, 94.8% and 85.4%with RSD of 4.1%, 3.6%, 4.4% and 3.9%, respectively. The content ranges of imtermedine, lycopsamine, imtermedine N-oxide, and lycopsamine N-oxide in the six batches of Scutellariae Barbatae Herba were 0.18—0.66, 0.11—0.42, 0.78—2.21 and 0.19—0.97 μg/g, respectively. The MOE values ranged from 3 134 to 6 461. Conclusion The method can be used for the determination of four pyrrolizidine alkaloids in Scutellariae Barbatae Herba, providing a scientific basis for the quality evaluation and safe medication of this herb. Preliminary risk assessment showed that long-term use of the drug has certain drug safety risks.

R917

科技部重大新药创制项目（2018ZX09735-006）