Methyclothiazide
;)
2H-1,2,4-Benzothiadiazine-7-sulfonamide,6-chloro-3-(chloromethyl)-3,4-dihydro-2-methyl-,1,1-dioxide,(±)-.
(±)-6-Chloro-3-(chloromethyl)-3,4-dihydro-2-methyl-2H-1,2,4-benzothiadiazine-7-sulfonamide 1,1-dioxide [135-07-9].
»Methyclothiazide contains not less than 97.0percent and not more than 102.0percent of C9H11Cl2N3O4S2,calculated on the dried basis.
Packaging and storage—
Preserve in well-closed containers.
Identification—
A:
Infrared Absorption á197Kñ.
Solution:
20µg per mL.
Medium:
methanol.
C:
Fuse about 100mg of it with a pellet of sodium hydroxide:the ammonia fumes produced turn moistened red litmus paper blue.The fused mixture responds to the test for Sulfite á191ñ.
Loss on drying á731ñ—
Dry it at 105
for 4hours:it loses not more than 0.5%of its weight.
for 4hours:it loses not more than 0.5%of its weight.
Residue on ignition á281ñ:
not more than 0.2%.
Chloride á221ñ—
Shake 750mg with 25mLof water for 2minutes,filter through a suitable membrane filter,and add 4or 5drops of 2Nnitric acid:the acidified filtrate shows no more chloride than corresponds to 0.20mLof 0.020Nhydrochloric acid (0.02%).
Selenium á291ñ:
0.003%.
Heavy metals,Method IIá231ñ:
0.002%.
Diazotizable substances—
Standard preparation—
Transfer about 10mg of USP Methyclothiazide Related Compound A RS,accurately weighed,to a 50-mLvolumetric flask,dilute with acetonitrile to volume,and mix.Pipet 25mLof the solution into a 100-mLvolumetric flask,dilute with acetonitrile to volume,and mix.Each mLof Standard preparationcontains about 50µg of the Reference Standard.
Test preparation—
Transfer about 500mg of Methyclothiazide,accurately weighed,to a 100-mLvolumetric flask,dissolve in and dilute with acetonitrile to volume,and mix.
Procedure—
Pipet 2mLeach of the Standard preparationand the Test preparationinto separate 50-mLvolumetric flasks.Pipet 2mLof acetonitrile into a third 50-mLflask to provide the blank.To each flask add 4mLof 0.1Nhydrochloric acid,and mix.Add 3.0mLof sodium nitrite solution (1in 200)to each flask,mix,and place the flasks in an ice bath for 5minutes,shaking occasionally.Add to each flask 3.0mLof ammonium sulfamate solution (1in 50),mix,and allow the flasks to remain in the ice bath for 1additional minute.Remove the flasks from the ice bath,add 1.0mLof N-(1-naphthyl)ethylenediamine dihydrochloride solution (1in 1000),and mix.Allow the flasks to stand at room temperature for 1minute,then dilute with water to volume,and mix.Concomitantly determine the absorbances of the solutions obtained from the Standard preparationand the Test preparationin 1-cm cells at 525nm,with a suitable spectrophotometer,using the reagent blank to set the instrument.The absorbance of the solution from the Test preparationdoes not exceed that of the solution from the Standard preparation,corresponding to not more than 1.0%of diazotizable substances.
Assay—
Transfer about 350mg of Methyclothiazide,accurately weighed,to a 250-mLconical flask,add 40mLof a 1in 20solution of potassium hydroxide in methanol,and reflux at full boil for 1hour.Cool,rinse the inner walls of the condenser with 20mLof water and two 20-mLportions of methanol,add 10mLof glacial acetic acid and 2drops of eosin Y TS,and titrate with 0.1Nsilver nitrate VSto the first appearance of a definite pink color.Each mLof 0.1Nsilver nitrate is equivalent to 36.02mg of C9H11Cl2N3O4S2.
Auxiliary Information—
Staff Liaison:Andrzej Wilk,Ph.D.,Senior Scientific Associate
Expert Committee:(PA5)Pharmaceutical Analysis 5
USP28–NF23Page 1254
Phone Number:1-301-816-8305