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Trimethoprim Sulfate
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(C14H18N4O3)2·H2SO4 678.73

2,4-Pyrimidinediamine, 5-[(3,4,5-trimethoxyphenyl)methyl]-, sulfate (2:1) (salt).
2,4-Diamino-5-[(3,4,5-trimethoxybenzyl)pyrimidine]-, sulfate (2:1) (salt) [56585-33-2].
» Trimethoprim Sulfate contains not less than 98.5 percent and not more than 101.0 percent of (C14H18N4O3)2·H2SO4, calculated on the anhydrous basis.
Packaging and storage— Preserve in well-closed containers. Store at 25, excursions permitted between 15 and 30.
A: Ultraviolet Absorption 197U
Solution— Transfer about 100 mg of it, accurately weighed, to a 100-mL volumetric flask, dissolve in 25 mL of alcohol, dilute with 0.1 N sodium hydroxide to volume, and mix.
Medium— Dilute the Solution quantitatively and stepwise with 0.1 N sodium hydroxide to obtain a solution containing a known concentration of about 20 µg per mL.
Absorptivity, at about 287 nm, calculated on the anhydrous basis, is between 83.0% and 86.4% of USP Trimethoprim RS.
B: It responds to the tests for Sulfate 191.
Melting range 741: between 210 and 215.
pH 791: between 7.5 and 8.5, in a solution (0.5 mg per mL).
Water, Method I 921: not more than 3.0%.
Chromatographic purity—
Adsorbent: 0.25-mm layer of chromatographic silica gel mixture.
Diluent— Prepare a mixture of chloroform and methanol (9:1).
Test solution— Transfer about 20 mg of Trimethoprim Sulfate, accurately weighed, to a 10-mL volumetric flask, add 4 mL of glacial acetic acid, and swirl to dissolve. Dilute with Diluent to volume, and mix.
Standard solution— Dissolve an accurately weighed quantity of USP Trimethoprim RS in Diluent. Dilute an accurately measured volume of this solution quantitatively, and stepwise if necessary, with Diluent to obtain a solution having a known concentration of 0.02 mg per mL.
Application volume: 10 µL.
Developing solvent system: a mixture of chloroform, methanol, and 6 N ammonium hydroxide (95:7.5:1).
Procedure— Proceed as directed for Thin-Layer Chromatography under Chromatography 621. Spray the plate with a freshly prepared mixture of 1.9 g of ferric chloride in 20 mL of water and 0.5 g of potassium ferricyanide in 10 mL of water. Compare the intensities of any secondary spots observed in the chromatogram of the Test solution with that of the principal spot in the chromatogram of the Standard solution: no secondary spot in the chromatogram obtained from the Test solution is larger or more intense than the principal spot obtained from the Standard solution (0.1%); and the sum of the intensities of the secondary spots obtained from the Test solution corresponds to not more than 0.5%.
Residual solvents 467: meets the requirements.
(Official January 1, 2007)
Assay— Transfer about 800 mg of Trimethoprim Sulfate, accurately weighed, to a 50-mL conical flask, add about 60 mL of glacial acetic acid, and titrate with 0.1 N perchloric acid VS, determining the endpoint potentiometrically. Perform a blank determination, and make any necessary correction. Each mL of 0.1 N perchloric acid is equivalent to 67.87 mg of (C14H18N4O3)2·H2SO4.
Auxiliary Information— Staff Liaison : Behnam Davani, Ph.D., MBA, Senior Scientist
Expert Committee : (MDAA05) Monograph Development-Antivirals and Antimicrobials
USP29–NF24 Page 2213
Pharmacopeial Forum : Volume No. 29(6) Page 1995
Phone Number : 1-301-816-8394