顶空气相色谱-质谱法测定布南色林原料药中遗传毒性杂质

目的：建立顶空气相色谱-质谱法测定布南色林原料药中甲磺酸甲酯、甲磺酸乙酯和甲磺酸异丙酯3种遗传毒性杂质含量的方法。方法：采用顶空气相色谱-质谱法，以甲磺酸丁酯为内标，按内标标准曲线法进行甲磺酸甲酯、甲磺酸乙酯和甲磺酸异丙酯的含量测定。色谱条件：DB-WAX毛细管色谱柱（30 m×0.25 mm×0.25 μm）；程序升温，初始柱温为40℃，维持3 min，升温速率为30℃·min^-1，终止温度150℃，保持2 min；进样口温度为110℃；载气（He）流速为0.6 mL·min^-1；进样量为1 mL；进样方式为分流进样，分流比为20：1。质谱条件：电子轰击离子源（EI），扫描方式为选择性离子检测；离子源温度为200℃；接口温度为150℃；电子能量为70 eV；溶剂延迟1 min。结果：3种杂质成分之间的分离度均大于2.0；甲磺酸甲酯、甲磺酸乙酯、甲磺酸异丙酯检测质量浓度线性范围均为0.025~3.0 μg·mL^-1（r ≥ 0.998 5）；精密度、稳定性、重复性试验的RSD<5%；加样回收率分别为93.40%~101.40%（RSD为3.2%，n=9）、92.80%~99.70%（RSD为2.5%，n=9）和96.30%~100.75%（RSD为1.6%，n=9）。结论：该方法简便、准确、灵敏、迅速，可用于布南色林原料药中3种遗传毒性杂质的测定。

Determination of genotoxic impurities in blonanserin raw material by head-space GC-MS

OBJECTIVE To establish a HS-GC-MS method for the determination of the genotoxic impurities (methyl methanesulfonate, ethyl methanesulfonate and isopropyl methanesulfonate) in blonanserin raw material. METHODS The contents of methyl methanesulfonate, ethyl methanesulfonate and isopropyl methanesulfonate were determined by HS-GC-MS method with butyl methanesulfonate as internal standard. Chromatography condition:DB-WAX capillary column (30 m×0.25 mm×0.25μm); temperature programmed, initial column temperature 40℃, 3 min, heating rate 30℃·min^-1, termination temperature 150℃, 2 min; injection port temperature 110℃; carrier gas (He) flow rate 0.6 mL·min^-1; injection volume 1 mL; injection mode:split injection, split ratio 20:1. Mass spectrometric conditions:electron impact ion source (EI), selective ion detection by scanning mode; ion source temperature:200℃; interface temperature:150℃; electron energy:70 eV; solvent delay:1 min. RESULTS Methyl methanesulfonate, ethyl methanesulfonate and isopropyl methanesulfonate were all 0.025~3.0 μg·mL^-1(r ≥ 0.9985); RSDs of precision, stability and repeatability tests were lower than 5.0%; The average recoveries ranged 93.40%~101.40% (RSD=3.2%, n=9)、92.80%~99.70% (RSD2.5%, n=9)and 96.30%~100.75% (RSD=1.6%, n=9). CONCLUSION The method is simple, accurate, sensitive and rapid for the determination of 3 genotoxic impurities in blonanserin.