Determination of Industrial Acotiamide Hydrochloride Trihydrate by High Performance Liquid Chromatography
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摘要:
盐酸阿考替胺三水合物为第一个胃肠蠕动改善药物, 用来治疗功能性消化不良, 作为一种新药, 其分析测定方面的报道甚少, 已有的报道采用高效液相色谱(HPLC)以甲醇-磷酸二氢钾-辛烷磺酸钠为流动相进行测定, 由于使用了离子对试剂辛烷磺酸钠, 因而分析过程比较耗时且保留不够稳定。本文基于盐酸阿考替胺三水合物为两性化合物, 建立了测定其含量的高效液相色谱分析方法。测定方法采用C18(4.6 mm×150 mm, 5 μm)色谱柱, 以甲醇-20 mmol/L乙酸铵水溶液=45:55(V/V)为流动相(pH 6.8) 进行等度洗脱, 紫外检测波长选择280 nm, 盐酸阿考替胺三水合物的保留时间合适且峰形较好, 出峰时间为8 min, 总分析时间为23 min。在优化色谱条件下, 盐酸阿考替胺三水合物的浓度在0.0006~1.0 mg/mL范围内线性关系良好, 检出限为0.0002 mg/mL, 日内、日间测定的相对标准偏差(RSD)均小于1.0%。该方法不添加离子对试剂, 有利于色谱系统的快速平衡, 提高了实验的重复性和可操作性, 可对盐酸阿考替胺三水合物工业品进行快速分析, 实现对原料药的质量控制。
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关键词:
- 高效液相色谱法 /
- 盐酸阿考替胺三水合物 /
- 辛烷磺酸钠 /
- 甲醇-乙酸铵 /
- 质量控制
Abstract:Acotiamide hydrochloride trihydrate, which is the first gastrointestinal prokinetic agent, has been proven effective in treating functional malnutrition. There is little method in analyzing this new medicine. The only reported method is using High Performance Liquid Chromatography (HPLC), with methanol-monopotassium phosphate-sodium octanesulfonate as the mobile phase. However, this method is time wasting and unstable because of the using of an ion paring agent in the mobile phase. In this paper, a new HPLC method is established to quantitatively analyze industrial acotiamide hydrochloride trihydrate based on its amphoteric structure. The separation is accomplished in a C18 (4.6 mm×150 mm, 5 μm) column with methanol and 20 mmol/L ammonium acetate aqueous solution (pH 6.8) (45:55, V/V) as the mobile phase. The detection wavelength is set at UV 280 nm. The retention time of acotiamide hydrochloride trihydrate is 8 min with good peak shape, and the total analysis time is 23 min. Under the optimized chromatographic condition, the calibration curve of acotiamide hydrochloride trihydrate is linear in the range of 0.0006 and 1.0 mg/mL, detection limit is 0.0002 mg/mL, and both the intra-and inter-day relative standard deviations (RSDs) are lower than 1%. This method contains no ion paring agent, benefiting the rapid balance of chromatographic condition and improving the analysis repeatability and maneuverability. The method can be performed for rapid detection of acotiamide hydrochloride trihydrate and used in the quality control of raw medicine.
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表 1 盐酸阿考替胺三水合物样品测定
Table 1. Determination of acotiamide hydrochloride trihydrate in crude samples
平行样品 日内测定含量(%) 日间测定含量(%) 1 92.04 92.19 2 91.31 92.47 3 92.17 92.21 4 92.07 91.46 5 92.47 92.68 平均值 92.01 92.20 RSD(%) 0.46 0.50 
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