摘要
建立了高效液相色谱法检测盐酸雷莫司琼及其对映异构体,并考察了高温、光照、强酸、强碱等影响因素对异构体杂质含量的影响,从而为该药物的制剂、工艺研究和贮藏条件选择提供参考。采用YMC Chiral NEA(R)色谱柱,以50 mmol/L磷酸二氢钠缓冲液(pH 5.2):乙腈(50:50)为流动相,检测波长306 nm。盐酸雷莫司琼对映异构体间的分离度大于1.5;(S)-型异构体杂质在0.04~1.00μg/ml范围内线性关系良好,定量限为0.032μg/ml,平均回收率为100.2%(RSD=0.32%)。影响因素考察结果表明,在强碱条件下,盐酸雷莫司琼会发生向(S)-型异构体转化,提示制剂处方工艺研究中须避免碱性因素的影响。本方法准确、稳定,可为本品的质量控制提供参考。
An HPLC method was established for the chiral separation and determination of ramosetron hydrochloride and its （S）-enantiomer. The effects of temperature, humidity, light, acid, alkali and oxidant on the enantiomeric conversion from （R）-configuration to （S）-configuration in ramosetron hydrochloride active pharmaceutical ingredients （API） were also investigated. A YMC chiral NEA（R） column was used, with the mobile phase of 50 mmol/L sodium dihydrogen phosphate buffer solution（pH 5.2）：acetonitrile（50：50）, at the detection wavelength of 306 nm. The resolution of the enantiomers was more than 1.5. It was linear for （S）-ramosetron hydrochloride in the range of 0.04-1.00 μg/ml, with LOQ of 0.032 μg/ml. Its average recovery was 100.2%, with RSD of 0.32%. The results of stability test revealed that ramosetron hydrochloride would undergo an enantiomeric conversion from （R）-configuration to （S）-configuration in alkaline environment, which suggested that alkalinity should be avoided during its preparation and formulation process. The established method was accurate and stable, which provided a quality control method for ramosetron hydrochloride.
作者
沈晨
夏旭
高文彦
曾珊珊
叶金翠
SHEN Chen;XIA Xu;GAO Wenyan;ZENG Shanshan;YE Jincui(Zhejiang Academy of Medical Science Hangzhou 310000)
出处
《中国医药工业杂志》
CAS
CSCD
北大核心
2018年第8期1155-1160,共6页
Chinese Journal of Pharmaceuticals
基金
浙江省科技厅项目(2014F10034
2016F50016和2017C33147)
浙江省卫生高层次创新人才培养工程项目
