气相色谱-热能分析仪法测定缬沙坦及其制剂中的N-二甲基亚硝胺

目的：建立气相色谱-热能分析法（GC-TEA法）检测缬沙坦原料药及其制剂中N-二甲基亚硝胺（NDMA）含量。方法：色谱条件，采用INERTROAP-WAX（30 m×0.32 mm×0.5μm）毛细管气相色谱柱，柱温为程序升温（初始温60℃，保持2 min，以10℃·min^-1升至120℃，保持1 min，以50℃·min^-1升至200℃，保持2 min），进样口温度230℃，不分流进样，进样量0.5μL；热能分析仪条件，接口温度250℃，热解室温度500℃，真空度59.85~66.5 Pa，氧气压力13.79 kPa；臭氧水平244（22.8 V）。结果：方法的专属性强，N-二甲基亚硝胺质量浓度在10~1000 ng·mL^-1的范围内呈线性（r=1.000，n=8），检测下限为3 ng·mL^-1；13批样品中NDMA含量为0~87.09×10^-6。结论：本方法可用于缬沙坦及其制剂中的NDMA检测。  

Objective: To establish a method based on gas chromatography-thermal energy analyzer method (GCTEA)to detect the content of N-dimethylnitrosamine (NDMA)in valsartan bulk drug and its preparation. Methods: Chromatography were performed on a column of INERTTROAP-WAX (30 m×0.32 mm×0.5 μm)capillary gas chromatography column, the column temperature was programmed to be 60℃ for 2 minutes, and then was raised at a rate of 10℃·min^-1 to 120℃ and held for 1 min, and was finally raised at a rate of 50℃·min^-1 to 230℃ and held for 2 min. Inlet temperature was 230℃, the injection volume was 0.5 μL with splitless injection; The thermal analyzer conditions were, interface temperature of 250℃, pyrolysis chamber temperature of 500℃. The degree of vacuum was 59.85 to 66.5 Pa, the oxygen pressure was 13.79 kPa, and the ozone level was 244 (22.8 V).Results: The method was specific. The NDMA had a good linear relationship in the range of 10-1 000 ng·mL^-1 (r=1.000, n=8), and the minimum detection limit was 3 ng·mL^-1;The NDMA content in 13 batches of sample was 0-87.09×10^-6. Conclusion: The established method can be used for the determination of NDMA in valsartan and its preparations. 

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