RP-HPLC法测定重酒石酸氢可酮原料药中有关物质的含量

Determination of the Related Substances in Hydrocodone Bitartrate Raw Material by RP-HPLC

目的:建立测定重酒石酸氢可酮原料药中8种有关物质吗啡、双氢可待因、可待因、羟考酮、可待因酮、甲基可待因、二苯甲酮和蒂巴因的方法。方法:采用梯度洗脱的反相高效液相色谱法。色谱柱为Inertsil ODS-2,以辛烷磺酸钠-乙腈组成流动相体系进行梯度洗脱,流速为1.5 mL.min-1,检测波长为283 nm,柱温为40℃。检测3批样品中的有关物质。结果:重酒石酸氢可酮与各有关物质分离良好,其中重酒石酸氢可酮、蒂巴因、二苯甲酮检测浓度线性范围分别为1.020 5～20.410 0、0.508 5～20.340、0.10～40.00μg.mL-(1r分别为0.999 7、0.999 9、1.000 0);检测限分别为0.05、0.005、0.005μg。3批样品中均未检出已知杂质峰。结论:本法简便、专属、灵敏,可用于重酒石酸氢可酮原料药有关物质的测定。

OBJECTIVE： To establish a method for the determination of related substances in hydrocodone bitartrat raw material,i.e.morphia,dihydrocodeine,codeine,oxycodone,codeinone,methylcodeine,benzophenone and thebaine.METHODS： RP-HPLC method was adopted with gradient elution.The determination was Inertsil ODS-2 column with mobile phase consisted of sodium octanesulphonate-acetonitrile（gradient elution） at the flow rate of 1.5 mL·min-1.The detection wavelength was set at 283 nm,and column temperature was 40 ℃.Related substances in 3 batches of samples were determined.RESULTS： Hydrocodone bitartrate was completely separated from related substances.The calibration curve of hydrocodone bitartrate was linear within 1.020 5～ 20.410 0 μg·mL-1（r=0.999 7）.The linear ranges were 0.508 5～20.340 μg·mL-1 for thebaine（r=0.999 9） and 0.10～40.00 μg·mL-1 for benzophenone（r=1.000 0）.The limits of detection were 0.05 μg for hydrocodone bitartrate and 0.005 μg for thebaine and benzophenone.Known impurity peak hadn＇t been detected in 3 batches of samples.CONCLUSION： The method is simple,selective and sensitive for the determination of related substances in hydrocodone bitartrate raw material.