高效液相色谱法定量分析硫酸特布他林特殊杂质3,5-二羟基-ω-叔丁基苯乙酮

HPLC Determination of Terbutaline Sulfate Impurity Ⅰ

目的建立硫酸特布他林特殊杂质3,5-二羟基-ω-叔丁基苯乙酮定量分析的高效液相色谱法。方法采用Kromasil C_(18)色谱柱(4.6 mm×150 mm,5μm),以缓冲液[己烷磺酸钠4.23 g溶于0.05 mol·L^(-1)甲酸钠溶液(用甲酸调节pH值至3.0)770mL]-甲醇(77∶23)为流动相,流速1.0 mL·min^(-1),检测波长为276 nm,柱温30℃,进样量20μL。采用加校正因子的面积归一化法对特殊杂质3,5-二羟基-ω-叔丁基苯乙酮进行定量分析。结果特殊杂质3,5-二羟基-ω-叔丁基苯乙酮与特布他林及其降解产物的分离度良好;该杂质质量浓度在0.10~579μg·mL^(-1)(r=1.000 0)内呈良好的线性关系;该杂质相对于硫酸特布他林的校正因子为3.6。结论本实验采用加校正因子的面积归一化法对已知杂质进行定量,既可以解决杂质对照品持续供应困难的问题,又可准确计算出杂质的真实含量,为质量控制提供了高效便捷的检测方法。

OBJECTIVE To establish a qualitative and quantitative HPLC method for the determination of impurity Ⅰin tebutaline sulfate. METHODS The Kromasil C18column（ 4. 6 mm × 150 mm,5 μm） was used as the analysis column; buffer solution [dissolving 4.23 g of sodium hexanesulfonate in 770 m L of 0. 050 mol ·L^-1ammonium formate solution（pH 3） ]-methanol（77 ∶ 23） was used as the mobile phase. The flow rate was 1.0 m L·min^-1,the column temperature was maitained at 30 ℃,the detection wavelength was set at 276 nm,and the injectiong volume was 20 μL. Area normalization method with correction factor was used for the quantitative analysis of the impurity Ⅰ. RESULTS Under the separation condition,the impurity Ⅰ was completely separated from the principal components. The calibration curve showed good linearity in the concentration range of 0. 10-579 μg·m L^-1（ r = 1. 000 0）.The correction factor was 3.6. CONCLUSION The area normalization method with correction factor developed in the paper can be used for the qualitative and quantitative analysis of the impurity Ⅰin terbutaline sulfate,which can not only solve the problem of the availability of impurity reference standards,but also reflect the actual contents of impurity. The method provides an efficient and convenient method for quality control of terbutaline sulfate.