Method Study For Quality Control Of Prifinium Bromide

Prifinium bromide is a kind of drugs which belong to neuromuscular blocking drugs. It has a spasmolytic effect and can treat functional bowel diseases and inhibit digestive tract convulsion and urethral convulsion. It also can be used to treat diseases in digestive system, gastrointestinal motility regulation, gastrointestinal motility inhibition and synthetic anticholinergic agents. From the chemical structure, Prifinium bromide is one of antimuscarinic drugs of quaternary ammonium radical.The study in this thesis is mainly focused on quality control method of Prifinium bromide. The aim is to establish an effective method to control the quality of this medicine, with a view to stability, effectiveness and security of drugs.Firstly detection of chemical structure of Prifinium bromide was concerned. Reference was used to identify the structure under the same conditions with the sample. The sample was analyzed to obtain main characteristics adsorption bands with an IR spectrum and other important information of the structure by using some spectral techniques including UV, MS, NMR and DSC, as well as a chemical method for the identification of bromine ion.Secondly, the thesis focused on studies of quality control methods of Prifinium bromide. They are:(1). According to synthesis routes of Prifinium bromide and degradation products, three important related substances were identified. On the basis of establishment of methodology to identify the related substances of Prifinium bromide, HPLC method was applied for the determination of related substances of Prifinium bromide. This method can effectively test and control related substances of Prifinium bromide. The column was ACE3C8-A1080,150mn×3mm,3μm), the mobile phase is ion pair solution:methanol(49:51)(Ion pair solution:weigh1.1511g85%phosphoric acid and1.0809g sulfonic acid sodium salt on1000mL volumetric flask, dilute to volume using water, that is), the detection wavelength is at215nm. The results showed that related substances test method of Prifinium bromide had a good specificity and a good linear relationship, with linear regression equation of y=32122x-119.77, correlation coefficient R=0.999(n=5), RSD=0.57%, the limit of detection of0.7ng. The analytical method was accurate, good reproducibility, and could be used in quality control of Prifinium bromide.(2). Methods of residual solvents including anhydrous ethanol, isopropyl alcohol, dichloromethane, petroleum ether(60～90), ethyl acetate, tetrahydrofuran and N, N-dimethylformamide in Prifinium bromide were established and validated in order to control their contents in the drug.(3).A non-aqueous titration method was established to determine content of Prifinium bromide. In view of precision, the method has been proved to be accurate, simple and feasible.Thirdly, methods of quality control including physical and chemical constants determination, identification, purity test, determination of content were studied. Physical and chemical constants determination included characters and solubility of Prifinium bromide; The identification was to identify the sample of Prifinium bromide with ultraviolet absorption spectrum, infrared absorption spectrum, HPLC and bromide identification; Purity tests included acidity, loss on drying, residue on ignition, heavy metals, related substances, organic residual solvents and content determination of Prifinium bromide.