首批盐酸西布曲明2个去甲基衍生物化学对照品的研制

Study on preparation of the first batch of reference standards of two desmethyl derivatives of sibutramine

目的:建立供含量测定用的盐酸西布曲明两个去甲基衍生物(盐酸N-单去甲基西布曲明和盐酸N,N-双去甲基西布曲明)的首批化学对照品。方法:应用UV、IR、NMR和ESI-MS对盐酸N-单去甲基西布曲明和盐酸N,N-双去甲基西布曲明对照品进行结构鉴定,并采用HPLC法、醇中碱电位滴定法和高氯酸非水电位滴定法进行纯度分析和含量测定。结果:HPLC测得两者的纯度分别为99.15%和99.33%;醇中碱电位滴定法测得两者的含量分别为101.3%和101.2%;高氯酸非水电位滴定法测得两者的含量分别为101.2%和100.6%。结论:本文中建立的醇中碱滴定法简便、准确、无汞污染,适用于盐酸西布曲明2个去甲基衍生物的含量测定。盐酸N-单去甲基西布曲明和盐酸N,N-双去甲基西布曲明对照品的建立为减肥类保健食品中非法添加西布曲明衍生物的检测和监督提供有力支持。

To establish the reference standards for two desmethyl derivatives （N - monodesmethylsib- utramine hydrochloride and N, N- didesmethylsibutramine hydrochloride） of sibutramine. Methods： Their struc- tures were identified by UV, IR, NMR, and ESI - MS spectrometry. Their purities were calculated by normalization method and self- contrasted dilution method. Their contents were determined by the methods of sodium hydroxide and perchloric acid potentiometric titration. Furthermore, loss on drying, residue on ignition, and hygroscopieity were tested. Results： Their purities were 99. 15% and 99.33% ,respectively by HPLC. Their contents were 101.3% and 101.2% ,respectively by sodium hydroxide in ethanol potentiometric titration, and were 101.2% and 100. 6% , re- spectively by non - aqueous titration. Conclusion ： Potentiometric titration carried out with sodium hydroxide （0. 1 mol · L- 1 ） in ethanol is suitable for determination of N -/N,N - di - desmethylsibutramine hydrochloride and the method is convenient, accurate, and mercury pollution -free. Meanwhile, the establishment of reference standards of desmethyl derivatives of sibutramine can efficiently control slimming drugs illegally added into functional foods.