Studies on Quality for Acamprosate Calcicum
|School||Huazhong University of Science and Technology|
|Keywords||Acamprosate calcium Homotaurine Related substances HPLC-ELSD content Residual solvent quality standards|
Acamprosate calcium structure similar to human endogenous neurotransmitter gamma-aminobutyric acid (GABA), its primary pharmacological action to get rid of alcohol dependence. Version 6.0 of the European Pharmacopoeia reproduces Acamprosate calcium, and its related substances have not been reported. The Wuhan Department drug Pharmaceutical Group developed the synthesis of the raw materials. Acamprosate calcium detailed quality studies. Of Acamprosate calcium synthesis intermediates - high taurine content and related substances determination method (HPLC-ELSD method); Acamprosate calcium determination method (HPLC) and with European Pharmacopoeia ion exchange resin - pH determined by titration method of comparison of the content; establish a of Acamprosate calcium related substances and Gas Chromatography residual solvent method; Acamprosate calcium formulate a scientific and reasonable quality standards. Provides a basis for the quality control of the raw material in the production process. The study is divided into four parts: First, the establishment of Acamprosate calcium intermediates in the synthesis of high taurine content and related substances determination method (HPLC-ELSD method). High taurine UV absorption detection methods usually capillary electrophoresis and high performance liquid chromatography, the process is complex and affected by many factors precolumn derivatization. Used in this experiment HPLC-ELSD method to 0.01mol · L-1 pentafluoropropionic acid solution (adjusted to pH 4.8) - methanol (80:20) as mobile relatively high taurine directly measured, it is possible to overcome this drawback, and related substances can also be quantitatively detected. Second, using the HPLC assay Acamprosate calcium content and with European Pharmacopoeia ion exchange resin - Acidimetric content method are compared. European Pharmacopoeia using ion exchange resin - acid-base titration to determine the content and tedious operation takes a long time, not specificity. This experiment measured by high performance liquid chromatography Acamprosate calcium content of raw materials, the mobile phase was 0.01mol · L-1 ammonium acetate solution (pH was adjusted with acetic acid to 5) - methanol (95:5). Flow rate: 0.5 ml · min-1, detection wavelength: 220nm, exclusive of of Acamprosate calcium HPLC method, precision, linearity and range, stability, accuracy, detection limit validation to ensure that the measuring method The test results are credible and effective, can be used for the study of the quality of the product. The content measured results of the method compared with the European Pharmacopoeia wears no significant differences. Three Acamprosate calcium material inspection and by gas chromatography detection of residual solvents. Using the HPLC method can detect content and related substances, not only to ensure the detection of a variety of substances, and to ensure that the content of the determination of the main peak purity, can control the quality of this product at a higher level. Acamprosate calcium synthesis process using methanol, ethanol, methylene chloride, Gas chromatography was used to detect the residual solvent, and the specificity of the GC method, precision, linearity and range, accuracy, limit of detection for authentication can be used for the control of the residual solvent of the raw materials finished. IV Acamprosate calcium corporate standards, three batches of samples for testing in accordance with the methodology developed in the European Pharmacopoeia and quality traits, solubility, identification, solution clarity and color, pH, high taurocholic acid, heavy metals, loss on drying, inspection and Determination of residual solvents, results show that three batches of samples required.