GC-MS法测定苯磺酸氨氯地平原料药中水合肼的含量

Determination of Hydrazine Hydrate in Amlodipine Besylate Raw Material by GC-MS

目的:建立苯磺酸氨氯地平原料药中基因毒性杂质水合肼含量的GC-MS方法。方法:采用DB-35MS(30 m×0.25 mm,0.25μm)分析柱,程序升温:65℃保持3 min,以25℃·min^(-1)升温至250℃,保持3 min,进样口温度为250℃;载气(氦气)流速为1.3 ml·min^(-1),以25∶1的分流比进样,进样体积为1μl。水合肼在丙酮-冰醋酸条件下进行衍生化反应,在SIM的扫描模式下对水合肼衍生物进行分析,其定量离子为m/z 112。结果:所测的水合肼衍生物在0.03~1.50μg·ml^(-1)浓度范围内线性良好(r=0.997 2),检测限为0.006 7μg·ml^(-1),定量限为0.02μg·ml^(-1),分析方法的专属性、重复性、中间精密度、准确度、溶液稳定性、耐用性等验证参数均在指导原则的规定范围内。结论:该GC-MS定量方法准确度高、重复性好、耐用性强,可用于苯磺酸氨氯地平原料药中水合肼的杂质检测。

Objective: To develop a GC-MS method for determining the content of hydrazine hydrate in amlodipine besylate. Methods: A DB-35 MS( 30 m× 0.250 mm,0.25 μ m) column was used,the column temperature was kept at 65 ℃ for 3 min,and then raised at 25℃·min^(-1) until the temperature reached 250℃,and then kept for another 3 min,and the temperature of injection inlet was set at 250℃.The flow rate of carrier gas( helium) was 1.3 ml·min^(-1),the sample was injected at a split ratio of 25∶1,and the injection volume was 1 μl. Hydrazine hydrate was derivatized under the condition of acetone and glacial acetic acid. The quantitative ion m/z 112 was scanned in the scanning mode of SIM. Results: The derivative product of hydrazine hydrate showed good linearity within the concentration range of 0.03-1.50 μg·ml^(-1)( r= 0.997 2). The limit of detection and quantification was 0.006 7 μg·ml^(-1) and 0.02μg·ml^(-1),respectively. All the validation parameters of the method including specificity,repeatability,intermediate precision,accuracy,solution stability and durability met the required acceptance of relevant method validation guidance. Conclusion: The GC-MS method has the advantages of high accuracy,good repeatability and strong durability. It can be used for the determination of hydrazine hydrate in amlodipine besylate.