盐酸雷莫司琼中有关物质测定方法的建立

 目的建立使用HPLC测定盐酸雷莫司琼原料中有关物质和右旋体的检测和控制方法。方法采用Diamonsil C₁₈色谱柱(4.6 mm×250 mm,5μm),以乙腈-0.05 mol·L^-1磷酸盐缓冲液(pH5.2)(30∶70)为流动相,流速为1.0 mL·min^-1,检测波长为210 nm,测定盐酸雷莫司琼原料中有关物质;采用CHIRAL NEA-R(4.6 mm×250 mm,5μm)手性柱,以乙腈-0.05mol·L^-1磷酸二氢钾溶液(pH5.2)(50∶50)为流动相,流速为1.0 mL·min^-1,检测波长为306 nm,检查样品中右旋体的含量。结果盐酸雷莫司琼与合成反应中的4个重要中间体,能够得到有效分离,控制总杂质不超过1.0%。S-(+)和R-(-)盐酸雷莫司琼的保留时间分别为10.2和8.9 min,分离度大于2.5。结论上述方法准确、简便、专属,适用于盐酸雷莫司琼中有关物质及右旋体检查。

Determination of Related Substances in Ramosetron Hydrochioride by HPLC

OBJECTIVE To develop a HPLC method for the determination of related substances and S-(+) enantiomer in ramosetron hydrochloride.METHODS A separation for its related substances was performed on a Diamonsil C₁₈ column(4.6 mm×250 mm,5 μm),and mobile phase was acetonitrile-0.05 mol·L^-1 phosphate buffer(pH 5.2)(30∶70) with a flow rate of 1.0 mL·min^-1.The detection wavelength was 210 nm.The other separation for S-(+) enantiomer was performed on a CHIRAL NEA-R column(4.6 mm ×250 mm,5 μm),and mobile phase consisted of acetonitrile-0.05 mol·L^-1 phosphate buffer(pH 5.2)(50∶50) with a flow rate of 1.0 mL·min^-1.The detection wavelength was 306 nm .RESULTS A satisfactory separation condition for the four related impurities and the sample was obtained.The total impurities were not more than 1.0%.The retention times for the S-(+) and R-(-) ramosetron hydrochloride were 8.9 and 10.2 min respectively with a resolution factor of more than 2.5.CONCLUSION The methods are simple,fast,accurate and specific,and can be used in the determination of related substances and S-(+) enantiomer in ramosetron hydrochloride.