Studies On Quality For Acamprosate Calcicum

Acamprosate Calcicum is a structural analogue of gaminobutyric acid (GABA). It is thought to decrease positive reinforcement of alcohol intake. Acamprosate Calcicum could be found in European Pharmacopoeia 6.0 version without its related substances. Wuhan Wuyao Pharmaceutical Company Ltd.made research and development of this drug. This paper studied on quality for Acamprosate Calcicum,established the determination method for the assay and related substance of homotaurine, intermediate of the synthesis of Acamprosate Calcicum (HPLC-ELSD), determination method for the assay of Acamprosate Calcicum (HPLC),as well as made comparison with determination of content with ion exchange resins - acid-base titration on the European Pharmacopoeia; and in accordance with ICH requirements,established determination of related substance and content of residual solvents of Acamprosate Calcicum by gas chromatography;established Acamprosate Calcicum quality control standard. This paper provides the basis for quality control for this raw material in the production process. This study is divided into four parts:First, it established the determination method for the assay and related substance of homotaurine (HPLC-ELSD). Homotaurine,which is without UV absorption,detection methods are usually pre-column derivatization reaction for HPLC,but the results were impacted by the extent of the pre-column derivatization,the related substance can not be founded out. In this experiment,HPLC-ELSD method,using 0.01mol?L-1 pentafluoropropioic acid (pH adjusted to 4.8) - methanol (80:20) can directly determine the assay of homotaurine,can overcome that shortcoming and related substances can be detected quantitatively.Second,it used HPLC method to determine content of Acamprosate Calcicum and compared with determination of content with the ion exchange resins-acid-base titration method in European Pharmacopoeia. The operation of ion exchange resin - acid-base titration is complex,long-time,weak exclusive.This experiment used high-performance liquid chromatography to determine content of Acamprosate Calcicum,the mobile phase was 0.01mol ? L-1 ammonium acetate solution (pH adjusted with acetic acid to 5) - methanol (95:5). Flow rate: 0.5ml ? min-1,detection wavelength: 220nm.The system suitability, precision,linearity and range,accuracy,detection limit were validated to make sure that the result of the test method is reliable,effective and suitable for the study of quality standard.This method measured the content compared with the European Pharmacopoeia method was no significant difference.Third,it established determination related substances and content of residual solvents of Acamprosate Calcicum by gas chromatography. Using the HPLC method can detect content and related substances,not only to ensure that a variety of related substances were detected,but also to ensure the peak purity,can control the quality at a higher level. Methanol,ethanol,methylene chloride were used in the synthesis of Acamprosate Calcicum. Gas chromatography was used to detect residues of these solvents. The system suitability, precision,linearity and range,accuracy, detection limit were validated. This method can be used to control residual solvents.Fourth,quality standards of Acamprosate Calcicum was established. In accordance with the European Pharmacopoeia and the quality research methods,three batches of samples were detected respectively in traits,solubility,identification,solution clarity and color,pH, homotaurine,heavy metals,loss on drying,residual solvents and cotent.It showed that the three batches of samples are up to the requirements.