目的 建立測定阿哌沙班原料藥中可能殘留的12種有機溶劑（甲醇、乙醇、丙酮、異丙醇、叔丁基甲醚、二氯甲烷、醋酸乙酯、四氫呋喃、三乙胺、原甲酸三甲酯、嗎啉、N，N-二甲基甲酰胺）的檢測方法。方法 采用頂空氣相色譜法，色譜柱為DB-624毛細管柱（30.0 m×0.53 mm×3.00 μm），載氣為高純度氮氣；頂空溫度為100℃，頂空平衡時間為20 min；柱溫40℃，維持6 min，以20℃/min升至220℃，維持10 min；氫火焰離子化檢測器（FID），進樣口溫度為250℃，檢測器溫度為250℃，體積流量為2.8 mL/min，分流比為5：1。結(jié)果 在考察的濃度范圍內(nèi)線性關(guān)系良好（r=0.999 4~0.999 9），12種殘留溶劑均完全分離，精密度試驗RSD值以及被測組分的平均回收率均符合要求。結(jié)論 該氣相色譜法操作簡單，準確度、靈敏度高，可用于檢測阿哌沙班原料藥中殘留的有機溶劑。

Objective To establish a method for determination of the twelve residual organic solvents, including methanol, ethanol, acetone, isopropanol, tert-Butyl methyl ether, dichloromethane, aceticether, tetrahydrofuran, triethylamine,trimethylorthofor-Mate, morpholine, N,N-Dimethylformamide in Apixaban bulks drug. Methods Gas head-space chromatography was applied to this study. The column was DB-624 silica capillary column (30.0 m×0.53 mm×3.00 μm) and the carrier gas was high purity nitrogen; The vial temperature was 100℃, and the vial time was 20 min. The Column temperature was kept at 40℃ for 6 min, then the temperature was raised to 220℃ at the rate of 20℃/min and subsequently sustained for 10 min. FID detector temperature and injection temperature were both 250℃. The N₂ flow rate was 2.8 mL/min. Split ratio was 5:1. Results Twelve kinds of solvents were completely separated and determined with a good linearity (r=0.9994-0.9999).The RSD values of precision experiments and the average recovery was in line with the requirements. Conclusion Theanalytical method is simple, accurate and sensitive, which could be used for determination of residual organic solvents in Apixaban bulks drug.