The Research In Quality Control Of Glucosamine Drugs

Glucosamine is a natural monosaccharide which is extracted from marineorganisms by sophisticated technology. Glucosamine an important part ofproteoglycan and it can be used to synthesize collagen and it can be easily absorbed byhuman body with no side effects. Glucosamine is always used as the medicine oftreating osteoarthritis. The mechanism of its action is to strongly stimulate cartilagecells to promote the synthesis of collagen and produce new articular cartilage andsynovial joints for the repairing of worn articular cartilage, and then restore normalphysiological function and muscle weakness function. Meanwhile, glucosamine alsohas a good restoration for damaged articular cartilage cells caused by long-term use ofanti-inflammatory.Glucosamine is very unstable, so it’s usually prepared into a salt form so as toincrease its stability. Three kinds of glucosamine drugs have been found in thedomestic drug market, which are glucosamine hydrochloride, glucosamine sulfate andglucosamine sulfate potassium chloride (sodium) complex salt. With the improvementof Chinese per capita income levels and awareness of health, the consumption ofglucosamine drugs in China also shows a rapid growth, and now China become thelargest producer of glucosamine drugs. However, the current quality standards ofglucosamine drugs exists serious problems. In response to the increasing number ofdrug safety testing projects and increasingly stringent pharmaceutical standards,glucosamine drugs have been included in the improvement projects of standards onchemical drugs. This project will undertake the task of improving the standards onglucosamine drugs. In order to strengthen the supervision, administration and qualitycontrol of glucosamine drugs, we will review, study and improve the existing qualitystandards.The research is divided into four parts:1. Verification of the detecting methods in the current quality standards.Nowadays methods of assaying glucosamine drugs in domestic and foreignstandards are quite different. While the European Pharmacopoeia uses the method of potentiometric titration and USA Pharmacopoeia uses the method of high performanceliquid chromatography, Chinese Pharmacopoeia uses the old method of colorimetry.This experiment reviewed some typical methods they use and confirmed that thesemethods certainly have problems and deficiencies.Deficiencies of the determination method in domestic standards include thefollowing:①the method of determination of glucosamine raw material wasout-dated;②the selection of chromatography separation mode was inappropriate;③Due to the inappropriate selection of detector, salt ions have been mistakenlyconsidered as the active group, therefore the method of assay on glucosamine does nottest glucosamine but its salt ion. It is obvious that the method of assaying glucosaminein domestic standards has serious defects and it has no specificity.Deficiencies of the determination method in foreign standards are in the following:the mobile phase system in the method of assaying glucosamine in USAPharmacopoeia was not suitable for detecting at195nm wavelength. The fact that thecoexisting substances in this system have no characteristic UV absorption at thiswavelength and the sensitivity of them were not less than glucosamine has causedinaccurate determination of the glucosamine drug.All the above shows that the methods of assaying glucosamine drugs in currentquality standards certainly have some problems. In order to provide some experimentalevidence for establishing a feasible and accurate method of assay on glucosaminedrugs, we reviewed, researched and improved the current quality standards in thisexperiment.2. Selection and optimization of the detective conditions for the determination ofglucosamine.The chromatographic conditions of the established method were selected andoptimized, which included the selection of chromatographic column, the mobile phasesystems, the detector, the column temperature and the solvent in this experiment. As aresult, we established a HPLC-UV method and a HPLC-RID method to determine thecontent of glucosamine. And both methods can determine glucosamine in a specific and accurate way. Except for the difference of detector, other chromatographicconditions were the same. The separation was achieved on NH2column with a mobilephase of Ammonium phosphate buffer (dissolve phosphate1.0mL into2000mL water,and use ammonia solution adjust the PH to7.5)-Acetonitrile（45:55）at a flow rate of0.6mL/min．The column temperature was35℃and the injection volume was20μ L.3. Methodological study and sample determination on glucosamine detectionIn order to judge the feasibility and applicability of the two methods, weestablished methodological study on both of them. The results show that all indicatorsin methodology comply with the requirements. Under the condition of not demandingthe sensitivity, both of the two methods were able to meet the requirements of thedetermination of glucosamine raw materials and were able to be applied to determineany kinds of formulations of glucosamine drugs. Furthermore, the HPLC-RID methodfor the determination of glucosamine drugs shows greater precision, recovery, and alower limit of quantification.4. Research on the improvement of other projects in current quality standardsBesides the methods of assaying glucosamine drugs, we also reviewed andstudied other items in current quality standards which include identification, sulfatecontent and related substances in this experiment.Through this research, the innovative points of this subject include①The factthat the method of assay on glucosamine drugs in current quality standards haveserious defects were confirmed. In our country, it has been a long time that the saltions and chloride ion have been mistakenly used as the active group glucosamine and tthe content of chloride instead of glucosamine has been detected. Therefore, it is not afeasible method;②A specific, accurate and feasible method of assaying glucosaminedrugs were established so that in the future, the standards can be uniformed based onthis study;③The whole quality standards were improved so that the quality ofglucosamine drugs can be guaranteed from the source and the security surveillance inthe drug production process and the quality of drugs can be improved.