胶束液相色谱法同时快速分离片剂中奥氮平及其相关物质A(英文)

A rapid micellar HPLC method for simultaneous separation of olanzapine and its related compound A in tablets

目的建立快速分离奥氮平及其相关物质A的胶束高效液相色谱新方法,探讨其分离机理。方法采用MicrosorbMV 100 C8色谱柱,流动相为含41.7 mmol/L的十二烷基硫酸钠、pH 2.5（用磷酸调节）的胶束溶液—乙腈（35∶65,V/V）,流速1.2 mL/min,柱温为40℃。并对方法进行方法学考察,包括专属性、精密度、稳定性、线性、准确度、最低检测限、最低定量限。结果该方法专属性强（分离度〉2.03,峰纯度〉996）,5 min内就可以测定不同片剂中奥氮平含量及其相关物质A。奥氮平标示量的百分含量为97.1%～100.4%;奥氮平相关物质A的含量为0.3%～0.6%。建立了溶质、流动相和固定相三者之间相互作用的胶束高效液相色谱模型,并基于此模型对可能的分离机理进行了详细讨论。结论该方法快速、准确、灵敏,可用于奥氮平片的质量控制。

Objective To establish a rapid method for separation of olanzapine and its related compound A in tablets by micellar high performance liquid chromatography and to discuss the possible separation mechanism.Methods The optimized separation conditions were performed using a mobile phase consisted of water（containing 41.7 mmol/L sodium dodecyl sulfate） acetonitrile（35：65, V/V） at p H 2.50（adjusted with phosphoric acid）,running at 1.20 m L/min through a C8 column at 40 °C. The chromatographic method was validated from specificity, precision, stability, linearity, accuracy, minimum limits of detection and quantification. Results The proposed method was highly specific（resolutions were〉2.03 and the peak purity factor were996）. The contents of olanzapine in tablets were determined and the limits test of olanzapine related compound A in tablets were examined by the proposed method in 5 minutes. The percentage contents of the labeled amount of olanzapine ranged from 97.1 % to 100.4 % and percentages of the olanzapine related compound A ranged from0.3 % to 0.6 % in olanzapine tablets. The possible separation mechanism was in detail discussed based on the model of possible interaction among solutes, the mobile phase and stationary phase in the micellar high performance liquid chromatographic system. Conclusion The method was rapid, accurate and sensitive and could be applied to control the quality of olanzapine tablets.