铝镁加混悬液中醋酸氯己定及其降解杂质含量测定方法的研究

目的：研究铝镁加混悬液中醋酸氯己定的提取方法，建立同时测定铝镁加混悬液中醋酸氯己定及其降解杂质对氯苯胺含量的高效液相色谱（HPLC）法。方法：醋酸氯己定在铝镁加混悬液中仅占0.01%，不能采用现行药典方法进行检测。本研究考察了铝镁加混悬液样品前处理提取醋酸氯己定的方法；采用高效液相色谱-梯度洗脱法测定铝镁加混悬液中醋酸氯己定及其降解杂质的含量。色谱柱为WondaSil C₁₈ Superb柱（4.6 mm×250 mm，5 μm），流动相A为磷酸盐溶液（取磷酸二氢钠27.6 g，加三乙胺10 mL，加水1 500 mL，搅拌使溶解后，用磷酸调节pH3.0，用水稀释至2 000 mL）-乙腈（70：30），流动相B为乙腈，梯度洗脱，流速1.5 mL·min^-1，检测波长239 nm，柱温40℃。结果：醋酸氯己定和对氯苯胺质量浓度分别在0.982~13.76 μg·mL^-1和0.002~0.042 μg·mL^-1范围内线性关系良好；平均回收率质量浓度分别为101.0%和102.8%，3批样品测定醋酸氯己定和对氯苯胺含量，按标示量计算分别为88.8%~90.2%和0.017%~0.019%。结论：所建立的铝镁加混悬液中醋酸氯己定的提取方法和HPLC测定方法准确、快速、简便，为制定铝镁加混悬液的质量标准提供了可靠的分析方法。

Objective: To study the extracting method of chlorhexidine acetate from almagate suspension,and to establish a high performance liquid chromatography (HPLC) method for simultaneous determination of chlorhexidine acetate and its degrading impurity p-chloroaniline in almagate suspension. Methods: Chlorhexidine acetate only accounted for 0.01% in almagate suspension and could not be detected according to the current pharmacopoeia method. This study investigated the preliminary treatment method of extracting chlorhexidine acetate from almagate suspension and the HPLC-gradient elution method was used to determine the content of chlorhexidine acetate and its degradation impurity in almagate suspension. The chromatographic column used was WondaSil C₁₈ Superb column (4.6 mm×250 mm,5 μm). Solution A was a mixture of phosphate solution and acetonitrile (70:30). Phosphate solution was prepared by dissolving 27.6 g of monobasic sodium phosphate and 10 mL triethylaminewere in 1.5 L of water,adjusted pH of the mixture with phosphoric acid to 3.0 and diluted with water to 2 000 mL. Solution B was acetonitrile,gradient elution. The flow rate was 1.5 mL·min^-1,the detection wavelength was 239 nm,the column temperature was 40℃. Results: There was a good linear relationship of chlorhexidine acetate and p-chloroaniline in the range of 0.982-13.76 μg·mL^-1 and 0.002-0.042 μg·mL^-1,respectively;the average recovery rate was of 101.0% and 102.8%,respectively. The contents of chlorohexidine acetate and p-chloroaniline were 88.8%-90.2%and 0.017%-0.019% with calculated by labeled amount,respectively. Conclusion: The established extracting method of chlorhexidine acetate from almagate suspension and HPLC determination method are accurate,rapid and simple,providing a reliable analysis method for the quality standard of almagate suspension.

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