Studies On Rapidly Screening And Confirmation Methods Of Sibutramine Hydrochloride In Chinese Traditional Patented Medicines And Health Supplements

The paper involves establishment of a rapidly screening method of sibutramine hydrochloride in Chinese traditional patent medicines（CTPM） and health supplements（HS）.The method can be employed to develop rapidly screening reagent kits for field analysis of sibutramine hydrochloride in CTPM and health supplements HS sampled in the drug stores that are inspected.Also,the method can be used as a method of screening analysis of CTPM and HS before instrumental analysis is carried out in laboratory in order to reduce the cost of analysis.CTPM and HS consist of complicated compounds,most of which are colorful substances.Without separation of those substances,the color reaction of the rapidly screening method may be heavily interfered,or the color reaction phenomenon can be hardly observed distinctly,thus the correct judge can be barely obtained.Benefit from the good solubility of sibutramine hydrochloride both in organic acid solvents and inorganic solution,firstly,the method uses an organic solvent to extract sibutramine hydrochloride,separating the interfering substances that are insoluble in organic solvents.Subsequently,an inorganic acid solution is used to perform a liquid-liquid extraction,extracting the object substance from the organic solvent and leaving in the organic solvent the interfering substances that are insoluble in inorganic acid solution. Finally,a precipitation reagent of quaternary ammonium salt is added to react with sibutramine hydrochloride,forming a pink precipitation that can be clearly observed.The paper built a new highly selective,rapid,simple operation,low cost method that is easy to grasp for the staff of basic drug administration and can be carried out at the site that needs to inspect.To extend the application of the method for basic drug administration can overcome the disadvantage of the current technic and dissolve the difficulty coming up in the administration work of food and drug,thus ensure the public health significantly.As a validation of the method,an administration sampling and examining of specific item of health supplements for weight reduction was carried out in Guangdong province.The staff of basic food and drug administration of the province used the rapidly screening reagent kits to screen samples and produced a very good result of the examination.Totally 820 samples were examined with the method and proved by the official method of HPLC-MS/MS.Only 8 of 820 results obtained by the rapidly screening method were false positive,and there is no false negative result. So the accuracy of the method was（820-8）/820×100%=99.02%,and error rate of the method was 0.98%.By increasing declustering potential to lead the quasi-molecular ion of sibutramine collision-induced dissociation take place before its entering Q₁,fragment ions were generated.With the fragment ions as precursor ions,information of the ESI—MS³ ions were acquired by mass-spectrum analysis in ESI-MS² mode with a tandem mass spectrometer and the fragmentation behavior of sibutramine was discussed,resulting in confirmation of 4 fragment ions generated in the fragmentation. Based on the determination of these 4 ions,a method of liquid chromatography-electrospray ionization-multi-reaction monitoring was established for the verification of sibutramine.The method is highly sensitive,and determination results are clear and easy for judgement.Having more than 4 identification points required in a official document,the method fully meets the requirement for the verification of sibutramine added in Chinese traditional patented medical preparation and dietary supplements.The paper also established a method of determination of sibutramine hydrochloride in CTPM and HS by ion-pair reverse phase high performance liquid chromatography,and the method was validated methodologically.