克拉霉素干混悬剂有关物质方法研究

Study on the related substances in clarithromycin for dry oral suspension

目的建立RP-HPLC法,测定克拉霉素干混悬剂的有关物质。方法采用Agilent 1260 Infinity LC液相色谱仪,色谱柱为YMC C_(18)(250mm×4.6mm,5μm)柱,以0.033mol/L磷酸二氢钾溶液-乙腈(55:45)(用85%磷酸溶液或2mol/L氢氧化钾溶液调节p H值至5.4)为流动相,检测波长205nm,柱温50℃。结果克拉霉素与9个已知杂质及其他未知杂质均能达到有效分离,克拉霉素及杂质E的线性范围分别为2~1000μg/m L(r=1.000)、0.9~6.75μg/m L(r=0.998);供试品溶液在室温25℃下的12h基本稳定。结论本方法灵敏,准确,专属性强,重现性好,可用于克拉霉素干混悬剂有关物质的测定。

Objective To develop an RP-HPLC method for the determination of related substances in clarithromycin for oral suspension. Methods The chromatographic separation was achieved on a YMC C18 （250mm×4.6mm, 5μm） with the Agilent 1260 liquid chromatography system. The mobile phases consisted of 0.033mol/L potassium dihydrogen phosphate solution-acetonitrile （55：45） （pH value is adjusted to 5.4）. The detection wavelength was 205nm, and the column temperature was 50℃. Results Good separation between clarithromycin and nine identified impurities and other unknown impurities could be achieved. Good linear relationship was observed in the concentration range of 2-1000μg/mL （r=l.000） for clarithromycin, 0.9-6.75μg/mL （r=0.998） for 6,11-di-O- methyl-erythromycin A（impurity E）. Sample solutions were stable at 25 ℃ within 12 hours. Conclusion The method is sensitive, accurate, specific and reproducible, which can serve as a reliable analytical method for the determination of related substances in clarithromycin for oral suspension.