Sulfamethizole
;)
Benzenesulfonamide,4-amino-N-(5-methyl-1,3,4-thiadiazol-2-yl)-.
N1-(5-Methyl-1,3,4-thiadiazol-2-yl)sulfanilamide [144-82-1].
»Sulfamethizole contains not less than 98.0percent and not more than 101.0percent of C9H10N4O2S2,calculated on the dried basis.
Packaging and storage—
Preserve in well-closed,light-resistant containers.
Clarity and color of solution—
Dissolve 1.0g in 20mLof water and 5mLof 1Nsodium hydroxide:the solution is clear and not more than pale yellow.
Identification—
A:
Infrared Absorption á197Mñ.
B:
To about 0.1g add 5mLof 3Nhydrochloric acid,and boil gently for about 5minutes.Cool in an ice bath,then add 4mLof a sodium nitrite solution (1in 100),add water to make 10mL,and place the mixture in an ice bath for 10minutes.To 5mLof the cooled mixture add a solution of 50mg of 2-naphthol in 2mLof sodium hydroxide solution (1in 10):an orange-red precipitate is formed,and it darkens on standing.
C:
To about 20mg suspended in 5mLof water add,dropwise,1Nsodium hydroxide until dissolved,then add 2or 3drops of cupric sulfate TS:a light green precipitate is formed,and it does not change on standing.
D:
The retention time of the major peak in the chromatogram of the Assay preparationcorresponds to that of the Standard preparationas obtained in the Assay.
Acidity—
Digest 2.0g with 100mLof water at about 70
for 5minutes,cool immediately to about 20,and filter.To 25.0mLof the filtrate add 2drops of phenolphthalein TS,and titrate with 0.10Nsodium hydroxide:not more than 0.50mLis required for neutralization.Save the remainder of the filtrate for the tests for Chlorideand for Sulfate.
for 5minutes,cool immediately to about 20,and filter.To 25.0mLof the filtrate add 2drops of phenolphthalein TS,and titrate with 0.10Nsodium hydroxide:not more than 0.50mLis required for neutralization.Save the remainder of the filtrate for the tests for Chlorideand for Sulfate.
Loss on drying á731ñ—
Dry it at 105for 2hours:it loses not more than 0.5%of its weight.
for 2hours:it loses not more than 0.5%of its weight.
Residue on ignition á281ñ:
not more than 0.1%.
Chloride á221ñ—
A25.0-mLportion of the filtrate prepared in the test for Acidityshows no more chloride than corresponds to 0.10mLof 0.020Nhydrochloric acid (0.014%).
Sulfate á221ñ—
A25.0-mLportion of the filtrate prepared in the test for Acidityshows no more sulfate than corresponds to 0.20mLof 0.020Nsulfuric acid (0.04%).
Selenium á291ñ:
0.003%.
Heavy metals,Method IIá231ñ:
0.002%.
Ordinary impurities á466ñ—
Test solution:
methanol.
Standard solution:
methanol.
Eluant:
acetone.
Visualization:
1.
Assay—
Mobile phase—
Prepare a filtered and degassed mixture of water,methanol,and glacial acetic acid (69:30:1).Make adjustments if necessary (see System Suitabilityunder Chromatography á621ñ).
Standard preparation—
Dissolve an accurately weighed quantity of USP Sulfamethizole RSin methanol to obtain a solution having a known concentration of about 0.4mg per mL.Quantitatively dilute a volume of this solution with Mobile phaseto obtain the Standard preparationhaving a known concentration of about 8µg per mL.
Assay preparation—
Transfer about 20mg of sulfamethizole,accurately weighed,to a 50-mLvolumetric flask,dilute with methanol to volume,and mix.Quantitatively dilute a volume of this solution with Mobile phaseto obtain the Assay preparationhaving a concentration of about 8µg per mL.
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 10-µm packing L1.The flow rate is about 1.0mLper minute.Chromatograph the Standard preparation,and record the peak responses as directed for Procedure:the column efficiency determined from the analyte peak is not less than 2000theoretical plates,the tailing factor for the analyte peak is not more than 2.0,and the relative standard deviation for replicate injections is not more than 2.0%.
Procedure—
Separately inject equal volumes (about 50µL)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 C9H10N4O2S2in the portion of Sulfamethizole taken by the formula:
2.5C(rU/rS),
in which Cis the concentration,in µg per mL,of USP Sulfamethizole RSin the Standard preparation,and rUand rSare the peak responses 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
USP28–NF23Page 1827
Phone Number:1-301-816-8394