氢溴酸山莨菪碱注射液有关物质及含量测定研究

目的 建立氢溴酸山莨菪碱注射液有关物质及含量测定的方法。方法 采用高效液相色谱法，色谱柱为Intersil ODS-3 C18柱（4.6 mm×250 mm，5 μm），以0.01 mol·L-1磷酸二氢钾溶液（含0.15%三乙胺，用磷酸调节pH值至6.5）-甲醇（70∶30）为流动相，柱温为35 ℃，流速1.0 mL·min-1，检测波长为220 nm。结果 氢溴酸山莨菪碱与阿托品、托品酸及其他强制破坏产生的降解产物峰分离度良好；氢溴酸山莨菪碱在0.25~2.5 mg·mL-1（r=1.000）、托品酸及阿托品在1~100 μg·mL-1（r=0.999）内线性关系良好；氢溴酸山莨菪碱检出限为为0.2 ng，阿托品及托品酸均为0.05 ng；氢溴酸山莨菪碱定量限为0.7 ng，阿托品及托品酸均为0.17 ng。氢溴酸山莨菪碱、阿托品、托品酸高、中、低3种浓度的平均回收率均在99.5%~100.8%内，RSD〈0.8%。结论 建立的液相色谱法快速、准确、专属性强，可用于氢溴酸山莨菪碱注射液的含量测定和有关物质检查。

Study on the Determination and Related Substances of Anisodamine Hydrobromide Injection

OBJECTIVE To establish a method to determine the content and related substances of anisodamine hydrobromide injection. METHODS The analysis was performed on an Intersil ODS-3 C18 column（250 mm×4.6 mm, 5 μm） and the mobile phase consisted of 0.01 mol·L-1 potassium dihydrogen phosphate solution（with 0.15% triethylamine, adjust pH to 6.5 with phosphoric acid） and methanol（70∶30）. The flow rate was 1.0 mL·min-1. The column temperature kept at 35 ℃, and the detection wavelength was 220 nm. RESULTS Main peak, atropic acid, atropine and other individual impurity peaks were separated. The anisodamine hydrobromide was linear in the range of 0.25-2.5 mg·mL-1（r=1.000）, atropine and tropic acid were linear in the range of 1-100 μg·mL-1（r=0.999）. The average recoveries of anisodamine hydrobromide, atropine and tropic acid were 99.5%-100.8% during tests in their high, middle and low concentrations. The anisodamine hydrobromide’s detection limit was 0.2 ng and the limit of quantification was 0.7 ng. The atropine and tropic acid’s detection limit were 0.15 ng and the limit of quantification was 0.17 ng. CONCLUSION The method is rapid, accurate, sensitive and reliable for content determination of anisodamine hydrobromide injection and its related substances.