Ciprofloxacin Hydrochloride 盐酸环丙沙星质量标准英文.doc

Ciprofloxacin HydrochlorideC17H18FN3O3HClH2O 385.82The product is 1- Cyclopropyl -6-fluoro-1, 4 -dihydro- 4 -oxo- 7- (1 -piperazinyl)- 3 -quinolinecarboxylic acidhydrochloridemonohydrate. It contains not less than 88.5% C17H18FN3O3 calculated on the anhydrous basis.Description A white to slightly yellow crystalline powder; almost odourless; bitter in taste.Soluble in water, slightly soluble in methanol or ethanol, almost insoluble in acetic ether or methylene dichloride.Identification (1) Dissolve a quantity of Ciprofloxacin Hydrochloride and Ciprofloxacin Hydrochloride RS in a quantity of 0.1mol/L Hydrochloride solution separately (every 5 mg Ciprofloxacin Hydrochloride add 1 ml Hydrochloride solution), and dilute them with ethanol to obtain a test solution containing 1 mg per ml and a standard solution containing 1 mg per ml. Dissolve a quantity of Ciprofloxacin Hydrochloride RS and Ofloxacin RS in a quantity of 0.1 mol/L Hydrochloride solution separately (every 5 mg Ciprofloxacin Hydrochloride add 1 ml Hydrochloride solution), and dilute them with ethanol to obtain a system suitability test solution containing 1 mg Ciprofloxacin Hydrochloride and 1 mg Ofloxacin per ml. Carry out the method of TLC as described under the CP( Appendix B)，separately apply 2 ml each of the three solutions above to a TLC silica gel F254 plate R, and develop the chromatogram in a solvent system consisting of a mixture of ethyl acetate, methanol and concentrated Ammonia Solution(5:6:2), until the solvent front has moved about three-fourths of the length of the plate. Remove the plate from the chamber and allow the plate to air-dry. Examine the plate in ultraviolet light at 254nm or 365nm. The location and color of the principal band obtained from the test solution corresponds to that obtained from the standard solution.(2) The retention time of principal peak of the test solution being examined in the chromatogram obtained in the Assay is identical with that of Ciprofloxacin Hydrochloride CRS.(3) The infrared absorption spectrum is concordant with the reference spectrum of Ciprofloxacin Hydrochloride CRS.(4) A solution of it responds to the tests for Chloride (Appendix ).Choose one from (1) and (2).DetectionPH An aqueous solution of 25mg per ml, PH 3.04.5( Appendix H).Clarity and colour of solution Dissolve 1.0g of the substance in 10 ml of water, the solution is clear; any colour produced is not more intense than that of reference solution Y4 or YG4(Appendix A).Related substance Dissolve a accurately weighed quantity of the substance in mobile phase A and dilute to obtain a test solution containing 0.5mg per ml; dilute a quantity of Ciprofloxacin Hydrochloride CRS with mobile phase A to obtain a reference solution containing 1mg per ml. Dissolve 15 mg of Impurity A RS in a mixture of 0.6ml of 6 mol/L ammonia solution and a quantity of water in a 100 ml flask, dilute to volume with water and mix well. Dilute 1 ml of the solution to100ml with mobile phase A and mix well, take it as the Impurity A CRS. Carry out the method for HPLC (Appendix D), using a column packed with octadecylsilane bonded silica, a mixture of 0.025mol/L phosphoric acid solution- acetonitrile(87:13) ( adjusted to PH 3.00.1 with triethylamine) as the mobile phase A, acetonitrile, gradiently elute as mobile phase B with flow rate of 1.5ml per min according to the table below.Dissolve a quantity of Ofloxacin CRS, Ciprofloxacin Hydrochloride CRS and Impurity CRS in mobile phase A and dilute to obtain a mixture of 5mg of Ofloxacin CRS, 0.5mg of Ciprofloxacin Hydrochloride CRS and 10mg of Impurity CRS. Inject 20ml of the mixture solution into the chromatograph, take 278nm as detection wavelength, and record the chromatogram, the retention time for the peak of Ciprofloxacin Hydrochloride is about 12 minutes. The resolution factor between the peaks of Ofloxacin, Ciprofloxacin Hydrochloride and Impurity complies with the related requirements. Inject 20ml of the reference solution into the chromatograph, take 278nm as detection wavelength, adjust the detection sensitivity to make the peak of main ingredient be about 20% of the sum of all the peaks.Inject 20ml of test solution, the reference solution and the impurity A CRS into the chromatograph, take 278nm and 262nm as detection wavelength, and record the chromatogram, the retention time for the peak of Ciprofloxacin Hydrochloride is 1, for impurity E, B, C, I, and D are separately 0.3, 0.6, 0.7, 1.1 and 1.2. The area of the peak in the chromatogram obtained with impurity A CRS (detected under 262nm) is not more than 0.3% calculated on peak area by external standard method. The areas of the peak in the chromatogram obtained with Impurity B, C, D and E (detected under 262nm) should not more than those of the principal peak obtained with reference solution(0.2%) calculated on peak area after correction (multiply correction factor of 0.7, 0.6, 1.4 and 6.7). The area of the peak in the chromatogram obtained with any other impurity (detected under 278nm) should not more than that of the peak obtained with reference solution (0.2%). The sum of all the impurity area after correction is not more than 3.5 times the area of the principal peak in the chromatogram obtained with the reference solution (0.7%). Disregard any peak obtained with the test solution that is less than 0.1 time the area of the principal peak in the chromatogram obtained with the reference solution.Time( minute)Mobile phase A (%)Mobile phase B (%)01000161000534060541000651000Toluene and ethanolDissolve 0.2g of the product accurately weighed to a headspace Vial in 5 ml of water, well closed, as the test solution; Measure accurately a quantity of Toluene and ethanol, and dilute with water to obtain a solution containing 0.05mg Toluene and 0.1mg of ethanol per ml. measure accurately 5 ml into headspace vial, well closed, as the reference solution. Carry out the method for determination of residual solvents (Appendix P),using a capillary column closed with 5% phenyl-95% methylpolysiloxane(or with the similar polarity stationary phase), maintaining the temperature of the column at 50, the incubation time of headspace temperature of headspace oven is 90, the incubation time of headspace vial is 30 min.Inject the reference solution to the headspace vial, record the chromatogram. The resolution between the peaks of Toluene and ethanol comply with the requirement. Inject the test and reference solution to the headspace vial, record the chromatogram. Calculate the content of toluene and ethanol respectively with respect to the peak area obtained in the chromatogram by external standard method, the result complies with the related requirements.Water 4.7%6.7%( Appendix M, method 1 A)Residue on ignition Not more than 0.1%( Appendix N), using 1.0g.Heavy metals Carry out the limit test for heavy metals (Appendix H, method 2), using the residue obtained in the test for Residue on ignition: not more than 0.002%.Assay Carry out the method for high performance liquid chromatogram (Appendix D)Chromatographic and system suitabilityUsing a column packed with octadecylsilane bonded silica and a mixture of 0.025mol/L phosphoric acid solution-acetonitrile(87:13) as the mobile phase previously adjusted to pH 3.00.1 with triethylamine. The detection wavelength is 278nm and the flow rate of mobile phase is 1.5ml per min. Dissolve a quantity of Ofloxacin CRS, Ciprofloxacin Hydrochloride CRS and Impurity 1 CRS in mobile phase and dilute to obtain a m