Studies On Quality Of Dexmedetomidine Hydrochloride

In this thesis, the quality of Dexmedetomidine hydrochloride was studied, and its quality standards were established.Objective:To establish assay methods for Dexmedetomidine hydrochloride, including characterisation, identification, testing, residual solvents, related substance, enantiomer, and content determination.Method:Through quality study of Dexmedetomidine hydrochloride, the assay method of characterisations, detection and inspection methods were established. A HPLC method was established for determination of the relevent substances in Dexmedetomidine hydrochloride. Stationary phase was C18column and the mobile phase was0.008mol/L sodium dihydrogen phosphate solution(using phosphoric acid to adjust the pH to6.5)-acetonitrile-triethylamine(65:35:0.3), and detection wavelength was210nm. A HPLC method was established for determination of the enantiomer in Dexmedetomidine hydrochloride. Stationary phase was CHIRALPAK AS-H(4.6mm×250mm) chiral HPLC column, and the mobile phase was N-hexane-ethanol-trifluoroacetic acid-diethylamine (95:5:0.3:0.05), and detection wavelength was210nm, with the flow rate0.5mL/min. A GC method was established for determination of the residual solvents, including ethanol, ether, tetrahydrofunan, dichloromethane and chloroform. Non-aqueous titration was used for content determination. The above-mentioned methods were also used for stability study of Dexmedetomidine hydrochloride.Result:Dexmedetomidine hydrochloride was white or almost white crystalline powder. It was easily deliquescent soluble in water, soluble in methanol and ethanol, practically insoluble in0.1mol/L hydrochloric acid and anhydrous ether, and insoluble in hexane and0.1mol/L sodium hydroxide. Its melting point was155℃～157℃, and specific rotation is+48°+54°. After the products were dried to constant weight at105℃, its loss was no more than1.0%. The weight percent of sulphated ash was no more than0.1%. The heavy metal content was no more than10ppm. Its pH was4.0～5.0, and its auqeous solution was clarify and colorless. Its IR spectra was in agreement with reference spectrum. The determination of related substances showed that the area of biggest single impurity was less than half of the principal peak of the reference solution (0.5%). The total area of impurity peak was less than the principal peak of reference solution (1.0%). The impurity peak of isomer was less than the principal peak of reference solution (1.0%). Residual solvents, including ethanol, ether, tetrahydrofunan, dichloromethane and chloroform, were all conformed with the regulations.Conclusion:Standards of characteristics, identification and inspections for Dexmedetomidine hydrochloride are feasible. Methods for determination of residual solvents are feasible and accurate. Assay methods for relevent substances and enantiomer determination have strong specificity and applicability, and can control the quality of the product effectively. The content determination methods are simple, accurate, sensitive and reproducible. Dexmedetomidine hydrochloride should be preserved shading and sealing according to the stability study results.The quality standard can control the quality of dexmedetomidine hydrochloride well, and can be used as quality control standards for dexmedetomidine hydrochloride.