N1-2-Pyrimidinylsulfanilamide monosilver(1+)salt [22199-08-2].
»Silver Sulfadiazine contains not less than 98.0percent and not more than 102.0percent of C10H9AgN4O2S,calculated on the dried basis.
Packaging and storage Preserve in well-closed,light-resistant containers.
A: Infrared Absorption á197Kñ.
B: The RFvalue of the principal spot in the thin-layer chromatogram of the Test solutionas obtained in the test for Chromatographic puritycorresponds to that obtained from Standard solution A.
C: Dissolve about 1g in 15mLof ammonium hydroxide and 15mLof water in a 50-mLvolumetric flask,dilute with water to volume,and mix:the solution so obtained responds to the tests for Silver á191ñ.
Particle size [NOTEPerform in subdued light.]Wrap a 1-Lflask in aluminum foil,add 0.5g of Silver Sulfadiazine,add 1000mLof a suitable isotonic solution,and mix for 2hours.Add 5or 6drops of a suitable dispersant.Place the container in an ultrasonic bath,sonicate for 15seconds,and immediately analyze,using a suitable electronic particle counter equipped with a population counter and 140-and 30-µm apertures.The average particle size is not greater than 10µm and the size of not more than 10%of the particles is greater than 40µm.
Loss on drying á731ñ Dry it at 105for 1hour:it loses not more than 0.5%of its weight.
Limit of nitrate
Standard solution Prepare a solution of potassium nitrate in water having a known concentration of about 200µg of nitrate per mL.
Test solution Transfer about 2g of Silver Sulfadiazine,accurately weighed,to a beaker,add 30.0mLof water,stir for 20minutes,and filter through a suitable,nitrate-free filter.
Procedure Pipet 3mLof the Test solutionand of deionized water to provide the blank into separate test tubes.Pipet 1mLof the Standard solutionand 2mLof water into a third test tube.Cool the three test tubes in an ice bath.Slowly add 7.0mLof cold chromotropic acid solution,prepared by dissolving 50mg of chromotropic acid in 100mLof cold sulfuric acid,to each test tube,while swirling,and allow the test tubes to remain in the ice bath for 3minutes after the addition of the chromotropic acid solution.Remove the test tubes from the ice bath,and allow to stand for 30minutes.Concomitantly determine the absorbances of the Test solutionand the Standard solutionat the wavelength of maximum absorbance at about 408nm,with a suitable spectrophotometer,against the blank.Calculate the nitrate content,in mg,in the portion of Silver Sulfadiazine taken by the formula:
0.01C(AU/AS),in which Cis the concentration,in µg per mL,of nitrate in the Standard solution;and AUand ASare the absorbances obtained from the Test solutionand the Standard solution,respectively:not more than 0.1%is found.
Standard solution A Transfer about 50mg of USP Silver Sulfadiazine RSto a 10-mLvolumetric flask,and dissolve in 3.0mLof ammonium hydroxide.Dilute with methanol to volume,and mix to obtain a solution having a known concentration of about 5mg per mL.
Standard solution B Dilute a volume of Standard solution Aquantitatively,and stepwise if necessary,with a mixture of methanol and ammonium hydroxide (4:1)to obtain a solution having a known concentration of about 0.05mg per mL.
Test solution Transfer about 50mg of Silver Sulfadiazine to a 10-mLvolumetric flask,and dissolve in 3.0mLof ammonium hydroxide.Dilute with methanol to volume,and mix to obtain a solution having a known concentration of about 5mg per mL.
Procedure Prepare a chromatographic chamber containing a mixture of chloroform,methanol,and ammonium hydroxide (7:4:1)as the developing solvent.[NOTEMix the chloroform and methanol,then add the ammonium hydroxide.]Separately apply 10-µLportions of Standard solution A,Standard solution B,and the Test solutionto a suitable thin-layer chromatographic plate (see Chromatography á621ñ)coated with a 0.25-mm layer of chromatographic silica gel mixture.Allow the spots to dry,and place the plate in the chromatographic chamber.When the solvent front has moved about three-fourths of the length of the plate,remove the plate from the chamber,mark the solvent front,and allow the solvent to evaporate.Examine the plate under short-wavelength UVlight:no secondary spot in the chromatogram of the Test solutionis larger or more intense than the principal spot obtained from Standard solution B(1.0%),and the sum of all secondary spots observed is not greater than 2.0%.
Silver content Transfer about 500mg,accurately weighed,to a beaker,add 150mLof water and 50mLof nitric acid,and stir for 15minutes.Titrate with 0.1Npotassium thiocyanate VSto a potentiometric endpoint,using a silver-based indicator electrode and a double-junction reference electrode.Perform a blank determination (see Titrimetry á541ñ),and make any necessary correction.Each mLof 0.1Npotassium thiocyanate is equivalent to 10.79mg of silver:not less than 29.3%and not more than 30.5%of silver is found.
Mobile phase Prepare a degassed solution consisting of water,acetonitrile,and phosphoric acid (900:99:1).Make adjustments if necessary (see System Suitabilityunder Chromatography á621ñ).
Diluting solution Transfer 100mLof ammonium hydroxide to a 1-liter volumetric flask,dilute with water to volume,and mix.
Internal standard solution Dissolve an accurately weighed quantity of sulfamerazine in Diluting solution,and dilute quantitatively,and stepwise if necessary,with Diluting solutionto obtain a solution having a known concentration of about 10mg per mL.
Standard stock solution Dissolve about 250mg of USP Silver Sulfadiazine RS,accurately weighed,in 100mLof Diluting solutionin a 200-mLvolumetric flask,and sonicate for five minutes.Add 25.0mLof Internal standard solution,dilute with Diluting solutionto volume,and mix.
Standard preparation Pipet 2.0mLof Standardinto a 50-mLvolumetric flask.Dilute with Mobile phaseto volume,and mix.
Assay preparation Transfer about 250mg of Silver Sulfadiazine,accurately weighed,to a 50-mLround-bottom centrifuge tube.Add about 35mLof methanol,tightly seal the tube with a cap containing an inert liner,and mix,using a vortex mixer,for about 15seconds.Centrifuge for 15minutes to separate the phases.Aspirate,and discard the methanol supernatant layer.[NOTECare should be taken to avoid aspirating any of the residue.]Pipet 25.0mLof Internal standard solutioninto a 200-mLvolumetric flask.Add about 30mLof Diluting solutionto the centrifuge tube,replace the cap,and mix,using a vortex mixer,for about 15seconds.Quantitatively transfer the contents to the 200-mLvolumetric flask,using the Diluting solutionto rinse the tube.Repeat the addition of 30mLof Diluting solution,mixing and quantitatively transferring three more times.Dilute with the Diluting solutionto volume,and mix.Sonicate if necessary to obtain dissolution of the residue.Pipet 2.0mLinto a 50-mLvolumetric flask,dilute with Mobile phaseto volume,mix,and filter.
Chromatographic system (see Chromatography á621ñ)The liquid chromatograph is equipped with a 254-nm detector and a 3.9-mm ×30-cm column that contains packing L1.The flow rate is about 2.0mLper minute.Chromatograph the Standard preparation,and record the responses as directed for Procedure:the resolution,R,between sulfadiazine and sulfamerazine is not less than 2.0,and the relative standard deviation for replicate injections is not more than 2.0%.
Procedure Separately inject equal volumes (about 10µL)of the Standard preparationand the Assay preparationinto the chromatograph,record the chromatograms,and measure the responses for the major peaks.Calculate the quantity,in mg,of C10H9AgN4O2Sin the portion of Silver Sulfadiazine taken by the formula:
200C(RU/RS),in which Cis the concentration,in mg per mL,of Silver Sulfadiazine in the Standard stock preparation;and RUand RSare the relative peak ratios obtained from the Assay preparationand the Standard preparation,respectively.
Auxiliary Information Staff Liaison:Behnam Davani,Ph.D.,MBA,Senior Scientist
Expert Committee:(PA7)Pharmaceutical Analysis 7