高效液相色谱法测定盐酸吉西他滨有关物质及其稳定性研究

Determination of Related Substances of Gemcitabine Hydrochloride by HPLC and Study on Its Stability

目的采用高效液相色谱法测定盐酸吉西他滨溶液中的有关物质,通过杂质量变化考察盐酸吉西他滨的稳定性。方法采用HPLC测定盐酸吉西他滨有关物质的量,考察了各破坏条件下以及室温放置对盐酸吉西他滨稳定性的影响。结果盐酸吉西他滨在各破坏条件下均主要检出杂质Z2;盐酸吉西他滨溶液在室温放置过程中,Z2的量随时间成比例增加,24 h时该杂质增加的量已经超过质量标准的20%(0.02%)。结论盐酸吉西他滨原料药在某些破坏条件下和溶液在室温放置过程中,杂质Z2增加明显,表明盐酸吉西他滨溶液不稳定。建立方法的专属性、线性等均良好,能用于原料药及其制剂中有关杂质检测。

OBJECTIVE To establish an HPLC method to determine the related substances of gemcitabine hydrochloride for quality control and observe the stability of gemcitabine hydrochloride. METHODS An HPLC method was used to detect the related substances in gemcitabine hydrochloride. The stability of gemcitabine hydrochloride under various degradation conditions and the stabil- ity of its solution at room temperature were studied. RESULTS Impurity Z2 was the main substance detected under each degradation conditions, the amount of Z2 increased proportionally with time at room temperature, and the increased amount exceeded the upper lim- it of quality standard by 20% （0. 02% ） at 24 h. CONCLUSION Impurity Z2 markly increases under some degradation conditions and at room temperature, indicating that gemcitabine hydrochloride solution is unstable. The HPLC method has good specificity and lin- earity, which is suitable for quality control of gemcitabine hydrochloride and its pharmaceutical preparations.