目的 建立HPLC法测定氢氯噻嗪原料药中有关物质。方法 采用Waters Symmetry C₁₈柱（250 mm×4.6 mm，5μm）；流动相A：0.02 mol/L磷酸二氢钾溶液（用磷酸调pH值至3.2）–甲醇–四氢呋喃（94：6：1），流动相B：0.02 mol/L磷酸二氢钾溶液（用磷酸调pH值至3.2）–甲醇–四氢呋喃（50：50：5）；梯度洗脱；检测波长为224 nm；体积流量为1.0 mL/min；进样量：20 μL；柱温：35℃；样品仓温度：10℃。结果 氢氯噻嗪、4-氨基-6-氯-1，3-苯二磺酰胺、氯噻嗪线性范围分别为0.030 06～6.011 00、0.030 01～6.002 00、0.030 08～6.015 00 μg/mL；4-氨基-6-氯-1，3-苯二磺酰胺、氯噻嗪的平均回收率分别为98.66%、99.17%，RSD值分别为1.53%、1.02%。结论 本法准确、可靠、专属性强，可以控制氢氯噻嗪原料药中有关物质，为质量标准提升提供参考。

Objective To develop a method for the determination of related substances in hydrochlorothiazide active pharmaceutical ingredients. Methods The analysis was performed on an Waters Symmetry C₁₈ column (250 mm×4.6 mm, 5 μm). The mobile phase A was 0.02 mol/L potassium phosphate monobasic buffer (pH 3.2)-methanol-tetrahydrofuran (94:6:1), and the mobile phase B was 0.02 mol/L potassium phosphate monobasic buffer (pH 3.2)-methanol-tetrahydrofuran (50:50:5) with gradient elution. The detection wavelength was 224 nm, the flow rate was 1.0 mL/min, injection volume was 20 μL, column temperature was 35℃, and sample temperature was set as 10℃. Results The calibration curve of hydrochlorothiazide, 4-amino-6-chlorobenzene-1,3-disulfonamide, and chlorothiazide were linear in the range of 0.030 06-6.011 00 μg/mL, 0.030 01-6.002 00 μg/mL, and 0.030 08-6.015 00 μg/mL. And the average recoveries were 98.66% and 99.17% and with RSD value of 1.53% and 1.02%, respectively. Conclusion The method is accurate, reliable, and specific for the determination of related substances in hydrochlorothiazide active pharmaceutical ingredients, which provides a reference for the improvement of quality standards.

R927.2