目的 建立了UPLC-MS/MS法測(cè)定半枝蓮中印美定、石松胺、印美定氮氧化物和石松胺氮氧化物等4個(gè)吡咯里西啶生物堿的含量，并根據(jù)測(cè)定結(jié)果進(jìn)行初步的風(fēng)險(xiǎn)評(píng)估。方法 采用ACQUITY UPLC HSS T3色譜柱（100 mm×2.1 mm，1.8 μm），以含0.05%甲酸和2.5 mmol/L甲酸銨的水溶液（A）及含0.05%甲酸和2.5 mmol/L甲酸銨的乙腈溶液（B）為流動(dòng)相，梯度洗脫；電噴霧離子源，正離子多反應(yīng)模式監(jiān)測(cè)，外標(biāo)法測(cè)定。采用暴露限值（MOE）法進(jìn)行風(fēng)險(xiǎn)評(píng)估。結(jié)果 印美定、石松胺、印美定氮氧化物和石松胺氮氧化物質(zhì)量濃度在0.974～97.400、0.992～99.200、1.024～102.400和1.012～ 101.200 ng/mL與峰面積呈現(xiàn)良好的線性關(guān)系（r>0.999）；平均加樣回收率分別為88.7%、93.2%、94.8%、85.4%，RSD分別為4.1%、3.6%、4.4%、3.9%。6批半枝蓮樣品中印美定、石松胺、印美定氮氧化物和石松胺氮氧化物的含量范圍分別為 0.18～0.66、0.11～0.42、0.78～2.21、0.19～0.97 μg/g，MOE值為3 134～6 461。結(jié)論 所建立的方法可同時(shí)測(cè)定半枝蓮中4個(gè)主要吡咯里西啶生物堿含量；初步風(fēng)險(xiǎn)評(píng)估顯示，該藥材存在一定的用藥安全風(fēng)險(xiǎn)。

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

科技部重大新藥創(chuàng)制項(xiàng)目（2018ZX09735-006）