Application Reserach On The New Detection Methods For High-molecular Weight Impurities In β-lactam Antibiotics

β-lactam antibiotics consist of penicillins and cephalosporins. The high-molecular weight impurities of antibiotics generally refer to the substances with relative molecular mass greater than the durg itself. The polymer is the main component of high-molecular weight impurities. It is commonly known as polymer. The polymer is the primary contributor of clinical antibiotic drug anaphylaxis. At present the test methods for highmolecular weight impurities in β-lactam antibiotics suffer from the following problems: 1) The separation efficiency is poor; 2) The analysis time is too long; 3) The reference substance for high-molecular weight impurities is not easily available. As a result, it is very important to improve the current test methods for analyzing high-molecular weight impurities. This study aims to develop new test methods for high-molecular weight impurities in β-lactam antibiotics. It can provide important information for the pharmaceutical companies to improve current processes and research dosage forms, then enhancing antibiotic drug quality. It also will benefit patient by providing safe and more effective medication. The primary contributions of this study include the following aspects:1) Test method for the measurement of the related substances in Azlo cillin sodium was improved by performing UPLC gradient elution. The met hod appears to afford low detection limit, high sensitivity and better accura cy. The profile of azlocillin impurities was established.2) High-molecular weight impurities in Azlocillin sodium were detect ed by LC-MS combined column-switching and online demineralization tec hnique.With the combination of Azlocillin impurity profile, the special imp urity in RP-HPLC which was associated with total high-molecular weight i mpurities could be found. Thus the RP-HPLC method could be used to cont rol the special impurity instead of the total high-molecular weight impuritie s.3) Polymers in Azlocillin sodium for injection were tested by supercrit ical fluid chromatography and UPC2-QTOF. The method affords high resol ution. Supercritical fluid chromatography condition was established for sep arating polymers in Azlocillin sodium. The polymers were prepared by pre parative SFC. Polymers in Cefuroxime axetil were tested by UPC2. The UP C2 method was hoped to resolve the limitation of Gel Permeation Chromato graphy. The method appears to provide high resolution. The chromatograph ic condition will be benefit for preparative SFC to prepare polymers.4) Impurities in Cefditoren pivoxil were identified by LCMS-IT-TOF. There are no polymers identified in Cefditoren pivoxil. 2D-LC-IT-TOF was used to characterize polymers in Ceftriaxone sodium. The research results of multistage mass shows that the first impurity in one-dimensional was pol ymer in Ceftriaxone sodium. It also confirms that Ceftriaxone sodium in th e GFC system, with the elution order is exactly according to molecular size.Through the research this method can be implied to control the polymers in other antibiotics. The MALDI-TOF was used to characterrize impurities w hich were prepared by GFC.