HPLC法同时测定瑞舒伐他汀钙原料药中12种有关物质

Simultaneous Determination of Twelve Related Substances in Rosuvastatin Calcium Bulk Drug by HPLC

建立了HPLC法同时测定瑞舒伐他汀钙(1)原料药中12种有关物质(2~13)。色谱柱采用Welch C18柱(4.6 mm×250mm,5μm),流动相A为1%三氟乙酸水溶液、乙腈和水(体积比1∶35∶65)的混合液,B为1%三氟乙酸水溶液、乙腈和水(体积比1∶90∶10)的混合液,梯度洗脱。检测波长为242 nm,流速为1.0 mL/min,柱温40℃。结果显示,1及其有关物质间的分离度均大于1.5,且在相应质量浓度范围内线性关系良好。1~13的检测限为0.028 95~0.06021μg/mL,定量限为0.09650~0.20071μg/mL。2~13的平均回收率(n=9)为94.59%~102.00%,RSD为0.79%~4.06%。3批1原料药测定结果显示,除有关物质3的含量<0.2%,其他各有关物质的含量均<0.1%,总杂含量<1.0%。该方法分离度好、灵敏度高、专属性强,适用于1中有关物质的测定。

An HPLC method for the simultaneous determination of twelve related substances(2-13) in rosuvastatin calcium(1) was established. The Welch C18column(4.6 mm×250 mm,5 μm) was used, and the analysis was carried out in the gradient elution mode, with a solvent mixture comprising of 1% trifluoroacetic acid in water, acetonitrile and water(1∶35∶65, volume ratio) as mobile phase A, and a solvent mixture comprising of 1%trifluoroacetic acid in water, acetonitrile and water(1∶90∶10, volume ratio) as mobile phase B. The detection wavelength was 242 nm, the flow rate was 1.0 mL/min, and the column temperature was 40 ℃. The results showed that the resolution between 1 and its related substances was greater than 1.5, and it was linear for 1-13 in the corresponding mass concentration ranges. The LODs of 1-13 were 0.028 95-0.060 21 μg/mL, and the LOQs were 0.096 50-0.200 71 μg/mL. The average recoveries(n=9) of 2-13 were 94.59%-102.00%, with the RSDs of 0.79%-4.06%.The determination results of three batches of 1 bulk drug showed that the contents of all related substances were less than 0.1% and the total impurity content was less than 1.0%, except related substance 3, whose content was less than 0.2%.The established method has good resolution, high sensitivity and specificity, which is suitable for the determination of related substances in 1.