Quality Standard Research Of MF

Rapid development of the synthesis of quinolone antibacterial drugs, with broad spectrum antimicrobial, not easy to produce drug resistance, long half-life,fewer adverse reactions, etc, it is used widely in recent years in clinical antimicrobial drugs. This topic using a variety of analytical techniques to study MF of quality standards, and various research methods were inspected completely, in order to develop quality standards of the MF.Firstly, according to the guiding principles of chemical structure confirmation, the structure of MF was evaluated. Including elemental analysis, UV absorption spectroscopy(UV),infrared absorption spectroscopy (IR), mass spectrometry (MS), nuclear magnetic resonance spectroscopy(1H-NMR), carbon nuclear magnetic resonance spectroscopy (13C-NMR), hydrogen-hydrogen correlation spectroscopy (H-H COSY), carbon-hydrogen correlation spectroscopy (HSQC, HMBC), nuclear magnetic resonance DEPT testing, differential thermal analysis, proved MF of chemical structure is consistent with the target compounds.Secondly, a simple method was developed by HPLC for the determination of related materials and Content in MF. A HPLC method for related substances and content in MF was established by studying on the chromatographic column, mobile phase, flow rate and column temperature, the liquid chromatography conditions as follows:Agilent1260HPLC;Column:Agilent ZORBAX Eclipse XDB-phenyl (4.6x250mm,5μm); The mobile phase was methanol:water phase (0.5mg/ml tetrabutyl ammonium hydrogen sulfate, lmg/ml potassium dihydrogen phosphate,2ml phosphate adjusted pH2)=28:72; Detection wavelength of293nm; column temperature was45℃; flow rate of1.3ml/min. The sample could be seperated goodly with the related materials by contrast test of positioning and destructive test of the sample. After testing, the content of related substances in three batches of samples were less than0.3%, the results of the determination are between98.0%-102.0%.Thirdly, gas chromatographic method for the determination of residual organic solvents in MF was established. Optimal conditions for gas chromatography:Gas Chromatograph:Agilent Technologies6890N; headspace sampler:Agilent7694E; Column:DB-wax (30.0m×0.53mm×1.00μm) capillary column; detector:flame ionization detector (FID), temperature:250℃; column temperature:40℃to maintain8 min, at a rate of40℃/min raised to200℃, keeping3min; carrier gas (pure nitrogen); constant pressure:pressure4psi, headspace temperature80℃, the equilibrium time20min, the sample volume2ml. After method validation, show that the method with good linearity, high sensitivity, good reproducibility. Three samples detected by the external standard method with peak area calculation, the residual of methanol and acetonitrile were less than the standard limit of0.3%,0.041%, other solvents were not detected.At the same time, the physicochemical characteristics and stability tests of MF were studied. Factors tests showed that the drug substance for strong light, high temperature and high humidity were stable; The results of6months accelerated tests and12months long-term tests show us that MF was stable in the circumstances with normal temperature and humility, but has little moisture absorption when humidity is high.After these series of tests, these studies supply principles for quality standards of MF, meanwhile, give reference to preparation of formulation development and production process design.