| OBJECTIVESThe pivotal items on the quality control in quality standards of raw-materrial-medicine such as content mensuration, the method of determining of the relaten substances are emended. The controllability and validity of quality of Lofexidine Hydrochloride technical quarantee are offered.METHODS1.Mensuration of the contentEthanolic potassium hydroxide (0.1mol/L) is selected to the titration; The method of potentiometric titration is Carry out to indicate the end-points with the intention of ensuration of Lofexidine Hydrochloride2.Examination of the Related Substancesself-control method is employed, in whinch the test solution of 1ml, is diluted accurately, into the reference solution of 100 ml.The method of high performance liquid chromatography is employed to measurate both the reference solution and the test solution, with the stipulation that the sum of the areas of all peaks is not greater than the area of the principal peak obtained in chromatogram (maximum1.0%). Chromatogramsing condition:C18 columniation as a column packed with octadecylsilane bond silica gel (diamonsilTM, 4.6mmx200mm,5μ); 210 nm as check wavelength; methanol-0.27% potassium dihydrogen phosphate (65:35) as the Mobile phase; velocity of flow 1.0ml/min, quantity of Inject 10μl3.Introduction of the configuration of oxidative productionA HPLC method of the determination of the related substances in oxidative production of Lofexidine ydrochloride is introduced, being compared to the spectrogram and the chromatogram of the configuration of oxidative production structure. Chromatogramsing condition:C18 columniation as a column packed with octadecylsilane bond silica gel (diamonsilTM,4.6mmx200mm,5μ); a mixture of methanol-water (adjusting to pH 6.5 with formic acid) solution (50:50) as the Mobile phase; velocity of flow1.0ml/min, MS condition:electrospray ionization,positive ion monitoring,scan range 100～1000(m/z), pressure 4.25kV,gas N2, velocity of flow0.75L/min, capillary temperature 150℃.RESULTS1.The mensuration of the contentThe method of potentiometric titration created in this essay is preferable in linearity in the spectrum of the injection quantity 0.1-0.3g, which is in capability of meeting the request of the injection quantity while analyzing the cinstant quantity. RSD of precision test is 0.1%and that of the capacity analutical mentod.when this method is employed to mensure each content of three groups of raw-material-medicine of Lofexidine Hydrochloride,the results of 99.7%,99.5% 99.8%,ofwhich the callback rates 100.2%,100.1%,100.1%,with RSD 0.06%, indicate the high precision of this method.2.Examination of the substancesThe results of the examination of the three groups of substances relating to the samples are 0.4%,0.4%,0.1%. The productions brought under the subversive conditions such as acid, alkali, heat and oxidation do not interfere the mensuration of main ingredients. The separation degree between the peaks of productions and the principal peak of main ingredients obtained in chromatogram are greater than 1.5.3.Introduction of the configuration of productionThrogh the analysis performed by HPLC-MS/MS and the ultraviolet radiation spectrogram, it can be conjectured that the configuration of one of the oxidative productions originating from ofexidine Hydrochloride is 2.6-dicholrophenol.CONCLUSIONS1.The method of potentiometirc titration, which is employed in the mensureation of Lofexidine Hydrochloride, is in high precision and consistency. Moreover, this method not only avoids the pollution of hydragyrum caused by the entry of mercuric acetate while the non-aqueus titration is employed, but also decreases the stimulation to humain'respiratory tract caused by acetic acid and perchloric acid. The application of the method of potentiometric titration in the mensuration of Lofexidine Hydrochloride is preferable to the method of non-aqueous titration.2.Compare with the methods recorded in 2005 edition of Chinese Pharmacopoeia, the chromatogram condition is optimized and the research of the systematic applicability is augmented in the method of examination of the related substances cerated in the essay The productions brought under the subversive conditions such as acid,alkali,heat and oxidation do not interfere the mensuration of main in gredients. The separation degree between the peaks of productions and the principal peak of main ingredients obtained in chromatogram are greater than 1.5. The method referred in this essay is proper to the examination of related subsrances of Lofexidine Hydrochloride3.It can be conjectured through the analysis that the configutration of one of the oxidative productions originating from Lofexidine Hydrochloride is2.6-dicholrophenol... |
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