高效液相色谱法测定西咪替丁片有关物质

Determination of related substances in cimetidine tablets by high-performance liquid chromatography

建立高效液相色谱测定方法测定西咪替丁片有关物质包括西咪替丁及6种西咪替丁杂质。选择Welch Xtimate^(TM)C_(18)色谱柱(250 mm×4.6 mm,5μm)为分离柱;以甲醇–水溶液(0.4 mL三乙胺、0.86 g的己烷磺酸钠加水780mL混合后用磷酸调pH 2.8)(体积比为24∶78)为流动相A,甲醇为流动相B,按梯度洗脱;流量为1.0 mL/min;柱温为30℃;检测波长为220 nm。西咪替丁及6种西咪替丁杂质色谱峰面积与质量浓度在10~200μg/mL内呈良好的线性关系,相关系数均大于0.999 8;方法检出限为0.022 5~1.742μg/mL。辅料空白加入3种浓度水平时7种化合物的平均回收率为97.3%~102.2%,测定结果的相对标准偏差为0.92%~3.32%(n=9)。该方法稳定可靠,适用于西咪替丁片有关物质的测定。

A high performance liquid chromatography method for the determination of related substances in cimetidine tablets was established, which including cimetidine and 6 kinds of cimetidine impurities. Xtimate^(TM)C_(18)(250mm×4.6 mm, 5 μm) chromatography column was selected as the separation column;Methanol-water solution(0.4 mL triethylamine, 0.86 g sodium hexane sulfonate and 780 mL water, then pH adjusted to 2.8 by phosphoric acid)(volume ratio was 24/78) was used as mobile phase A, and methanol was used as mobile phase B, which was eluted by gradient at the flow rate of 1.0 mL/min, and the column temperature was 30 ℃, the detection wavelength was 220 nm. The mass concentration of cimetidine and six kinds of cimetidine impurities had a good linear relationship with the chromatography peak in the range of 10-200 μg/mL, and the correlation coefficients were all more than 0.999 8, the detection limits of the method were 0.022 5-1.742 μg/mL. The average recoveries of the seven compounds were 97.3%-102.2% when 3concentration levels were added in the excipients blank, and the relative standard deviations of the determination results were 0.92%-3.32%(n=9). The method is stable, reliable and suitable for the determination of related substances in cimetidine tablets.