Study On Quality And Stability Of Landiolol Hydrochloride

Landiolol hydrochloride was first developed by the Japanese Ono Pharmaceutical Industry Co, Ltd.And in the first it was listed in the emergency treatment of operation that occurs tachycardia sexual arrhythmias (including atrial fibrillation, on the left atrium, sinus sexual tachycardia) in September 2002.In October 2006, additional indications for surgery under the supervision of the dynamic cycle of tachycardia arrhythmias (including atrial fine move, atrial coarse, sinus tachycardia) was approved for emergency treatment in Japan. It has not been registered in China. To meet the variety of clinical needs of the domestic, the company developed its raw materials landiolol hydrochloride lyophilized.On the basis of information from literature, the modern research conditions and the molecular structure of itself, this thesis studies quality research methods of hydrochloric.Determine the appropriate testing conditions by high performance liquid chromatography and other modern analytical techniques,and the drafting of a scientific and rational development of quality standards, and its stability were investigated for the control of product quality and the development of quality standards to provide the test data.1 Study on the quality of landiolol hydrochlorideIn this thesis,the characteristics of landiolol hydrochloride were investigated through apearance, solubility illumination test and moisture test and this produet was proved to have no significant moisture.Landiolol hydrochloride is identified mainly by chemical identification method, UV spectrophotometry, retention time of HPLC, infrared spectrum and differential response of chloride.This product is used for injection of raw materials. According to the chemical properties of the materials and preparation process, it is determined the related substances, acidity, clarity and color of solution, dry weight loss, heavy metals, residue on ignition and residual solvents used in the synthesis of inspection, isomers such as the product of the inspection items.Because of the molecular structure of the product and the characteristics of synthesis, the material became the focus of the study product quality. The variety of related substances were determined by high performance liquid chromatography.The appropriate chromatographic conditions to detect were determined by method validation.Because the characteristics of the molecular structure of this product contains two chiral carbon, four isomers, isomers may be difficult to take into account the split, select the CHIRAL-CBH column (5μm,150mm×4.0mm).The results of methodology show that the method specificity, reproducibility and sensitivity are in line with determined requirements.According to "Chinese Pharmacopoeia" 2005 edition, AppendixⅧP, the determination of residual organic solvents and ICH requirements for drug introduced in the production process of harmful organic solvent residue to be checked. According to the synthesis route of the product, the second class of solvents methanol, hexane, and the third solvent ethanol, dimethyl sulfoxide, ethyl acetate, acetone. Reference to the guiding principles of limited standards, regulations of methanol, hexane, ethanol, dimethyl sulfoxide, ethyl acetate, acetone least were 0.3%,0.029%,0.5%,0.5%,0.5% and 0.5%.Residual solvent in the basic raw material was not detected,raw materials have been solvent residues can be effectively controlled without internal standard method, the performance indicators of methodology was verified and the result method is feasible.According to the nature of the product,high performance liquid chromatography method for the determination of hydrochloric acid contents landiolol methods and method validation carried out, including linear and scope, recovery, precision, solution stability, and through the potential titration confirmed the accuracy of high performance liquid chromatography.The study of quality above provide the test data for the control of product quality and the development of quality standards. 2 Quality standard and drafting instruction of landiolol hydrochlorideIn a comprehensive study on quality, combined with the actual situation, formulate a scientific and reasonable quality standard, including the character, identification, determination and so on. Determination of physical constants are mainly using chemical methods, UV spectroscopy, HPLC, identification of the differential response of chloride hydrochloride landiolol, content was determined by high performance liquid chromatography and related substances by gas chromatography solvent residues. Others include residue on ignition, heavy metals, dry weight loss and so did the experiment carefully.Development of drafting instructions for the project quality standards and indicators of reasonable and necessary to do further instructions.3 Stability examine of landiolol hydrochlorideOn the basis of quality standards above, in accordance with the requirements of Pharmacopoeia Appendix,conducted stability study of landiolol hydrochloride, including the influence factor tests, accelerated testing and long-term stability test. The results showed that hydrochloric acid landiolol more stable to light, high temperature (60℃) somewhat less stability, instability of humidity.The results for the hydrochloric acid landiolol storage conditions and provides the basis for the development period, as well as the quality of preparation process and the preparation provided reliable information.