消旋山莨菪碱片有关物质的研究

目的:针对个别企业使用不符合中国药典要求的原料非法投料生产消旋山莨菪碱片的情况,建立HPLC法测定消旋山莨菪碱片的特定杂质阿托酸6β-羟基-3α-托品酯,以监督和促使生产企业规范投料。方法:采用SHISEIDO CAPCELL C₁₈(250 mm×4.6 mm, 5μm)色谱柱,以0.01 mol·L^-1磷酸二氢钾溶液(含0.15%三乙胺,以磷酸调节pH 6.5)-甲醇(70:30)为流动相,流速1.0 mL·min^-1,检测波长220 nm,柱温35℃,进样量20μL。结果:杂质阿托酸6β-羟基-3α-托品酯质量浓度在4.52~45.2μg·mL^-1范围内线性关系良好,回归方程为Y=19.88X+0.9458, r=1.000,高、中、低浓度的回收率(n=3)分别为99.0%、99.2%、99.0%, RSD分别为0.1%、0.8%、0.6%。230批样品均检出该杂质,其中部分批次该杂质的含量较高。结论:该方法经方法学验证,可用于监督和促使生产企业在消旋山莨菪碱片生产过程中规范投料。

Objective:Targeting at several enterprises using active pharmaceutical ingredients which do not meet the requirements of Chinese pharmacopoeia in productive process, to establish an HPLC method for determination of specified impurity(atropic acid 6β-hydroxyl-3α-tropine ester)in raceanisodamine tablets to supervise and urge enterprises to regulate production. Methods:The separation was performed on a SHISEIDO CAPCELL C 18 column(250 mm×4.6 mm, 5μm), the mobile phase was 0.01 mol·L^-1 potassium dihydrogen phosphate solution(including 0.15% triethylamine, adjusted to pH 6.5 with phosphoric acid)-methanol(70:30), the flow rate was 1.0 mL·min^-1 and the detection wavelength was 220 nm. The column temperature was 35℃ and the injection volume was 20μL. Results:Good linear correlation of atropic acid 6β-hydroxyl-3α-tropine ester was found in the range of 4.52-45.2μg·mL^-1,and the linear equation was Y=19.88X+0.9458, r=1.000. The recoveries of high,medium and low concentrations(n=3)were 99.0%,99.2% and 99.0% respectively;and RSDs were 0.1%, 0.8% and 0.6%, respectively. The impurity was detected in all 230 samples, and some of the samples were found to have high content of impurity. Conclusion:The method can be used for supervising and urging enterprises to regulate production of raceanisodamine tablets.

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