目的 建立枸櫞酸坦度螺酮原料藥中間體中潛在基因毒性雜質(zhì)1，4-二溴丁烷的控制檢測方法。方法 采用高效氣相色譜（GC）法，使用色譜柱Agilent DB-624（30 m×320 μm，1.8 μm），升溫程序：初始柱溫95℃，保持2 min，以20℃/min升溫至220℃，保持5 min。進(jìn)樣口溫度250℃，檢測器溫度250℃，體積流量3 mL/min；分流比1∶1；進(jìn)樣量1 μL。進(jìn)行專屬性、線性范圍、靈敏度、穩(wěn)定性、重復(fù)性、回收率、耐用性方法學(xué)考察。結(jié)果 1，4-二溴丁烷在0.109 5～1.094 8 μg/mL內(nèi)峰面積與質(zhì)量濃度線性關(guān)系良好（r=0.998 6）；檢測限為0.109 5 μg/mL，定量限為0.273 7 μg/mL，平均回收率為116.2%，方法學(xué)考察均符合要求。各批次樣品中1，4-二溴丁烷的質(zhì)量分?jǐn)?shù)均小于0.002 5%。結(jié)論 建立的方法專屬性強(qiáng)、靈敏度高、測定結(jié)果準(zhǔn)確、操作簡單，可用于枸櫞酸坦度螺酮原料藥中間體中1，4-二溴丁烷的檢測。

Objective To establish a controlled method for the detection of the potential genotoxic impurity 1, 4-dibromobutane in the intermediate of tandospirone citrate API. Methods Agilent DB-624 (30 m×320 μm, 1.8 μm) was used. The initial column temperature was 95℃ for 2 min, and the temperature was 20℃/min to 220℃ for 5 min. The injection port temperature was 250℃, the detector temperature was 250℃, the flow rate was 3 mL/min, the split ratio was 1:1, and the injection volume was 1 μL. Results The linear range of 1, 4-dibromobutane was 0.109 5-1.094 8 μg/mL (r=0.998 6); the limit of detection was 0.1095 μg/mL, the limit of quantification was 0.273 7 μg/mL, the average recovery (n=9) was 116.2%, and the content of 1, 4-dibromobutane in each batch was less than 0.002 5%. Conclusion The method is specific, sensitive, accurate and simple. It can be used for the determination of 1, 4-dibromobutane in the intermediate of tandospirone citrate.

R917