佐匹克隆有关物质及其校正因子影响因素的测定研究

Study on the Determination of Zopiclone Related Substances and the Influence of Correction Factor

目的:测定佐匹克隆原料中的3种已知杂质和催化剂的相对校正因子,并对相对校正因子的影响因素进行考察。方法:采用高效液相色谱法,色谱柱为Kromail Eternity-5-C_(18)(4.6 mm×250 mm,5μm);流动相为乙腈-磷酸盐溶液(取十二烷基硫酸钠8.1 g与磷酸二氢钠1.6 g,加水1000 mL使溶解,用磷酸调节pH值至3.8)(41.5∶58.5);流速为1.0 mL·min^(-1);检测波长为303 nm;柱温为30℃。结果:佐匹克隆原料中的3种已知杂质和催化剂的出峰顺序分别为杂质B、杂质C、催化剂(以下简称杂质D)和杂质A,各已知杂质的相对校正因子(相对于佐匹克隆)分别为0.629、0.603、0.828和1.099,4种已知杂质及佐匹克隆主峰均能有效分离,最小分离度可达到1.5以上。佐匹克隆的线性范围为7.033×10-2μg·mL^(-1)~3.2460μg·mL^(-1),线性方程为y=30.579 x+0.5783,相关系数为R^(2)=0.9998。结论:该法可作为控制佐匹克隆原料有关物质的质量标准,对已知杂质和催化剂校正因子的影响因素考察结果可作为质控参考。

Objective:To determine the relative correction factors of the known impurities and catalyst of Zopiclone by HPLC,and to investigate the influence of the relative correction factors.Methods:Chromatographic column is Kromail Eternity-5-C_(18)(4.6 mm×250 mm,5μm).Mobile phase is acetonitrile-phosphate solution(Take 8.1 g sodium lauryl sulfate and 1.6 g sodium dihydrogen phosphate,add 1000 mL of water to dissolve it,use Phosphoric acid adjusts the pH value to 3.8)(41.5∶58.5).The flow rate is 1.0 mL·min^(-1).The detection wavelength is 303 nm and the column temperature is 30℃.Results:The peak sequence is impurity B、impurity C、catalyst(hereinafter referred to as impurity D)and impurity A,and the relative correction factors(relative to zopiclone)are 0.629,0.603,0.828,and 1.099.The seperation degree between impurities and Zopiclone can reach more than 1.5.The linear range of Zopiclone is:7.033×10^(-2)μg·mL^(-1)-3.2460μg·mL^(-1),the linear equation is:y=30.579 x+0.5783,and R^(2)=0.9998.Conclusion:This method can be used to control the related substances of Zopiclone,and the results on the influence of correction factors can also be used as a quality control reference.