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SULFAMETHOXAZOLE

Category Antibacterial; antiprotozoal.

      Sulfamethoxazole contains not less than 98.5 per cent and not more than 101.0 per cent of C10H11N3O3S, calculated on the dried basis.

Description White or off-white, crystalline powder. 

Solubility Practically insoluble in water, in ether and in chloroform; freely soluble in acetone and in dilute solutions of sodium hydroxide; sparingly soluble in ethanol.

Contra-indication It is contra-indicated in patients with history of hypersensitivity to sulfonamides or chemically related drugs (e.g., furosemide, thiazidediuretics, sulfonylureas, or carbonic anhydrase-inhibitors), in those with porphyria, severe renal or hepatic failure, intestinal and urinary obstruction, blood disorders, systemic lupus erythematosus, glucose-6-phosphate dehydrogenase deficiency (G-6-PD), in infants under 2 months of age (except in the treatment of congenital toxoplasmosis as adjunctive therapy with pyrimethamine), in pregnancy at term, and during the nursing period.

Warning

      1. Deaths from hypersensitivity reactions including Stevens-Johnson Syndrome, toxic epidermal necrolysis, fulminant hepatic necrosis, agranulocytosis, aplastic anemia, and other blood dyscrasias, irreversible neuromuscular and CNS changes, and fibrosing alveolitis have been reported. Hemolytic anemia, frequently dose-related, may occur in G-6-PD individuals.

      2. It should be used with caution in patients with impaired renal or hepatic function.

      3. It may cause nausea, vomiting, hypersensitivity reactions, renal and hepatic impairment, porphyria, blood dyscrasias, or megaloblastic anemia.

      4. Caution should be exercised if it is to be used concomitantly with p-aminobenzoic acid derivatives, oral anticoagulants, methotrexate, nonsteroidal antiinflammatory drugs, anticonvulsants, or antidiabetic agents.

      5. Risk-benefit must be considered before using this medicine in pregnant women.

Precaution

      1. Periodic determinations of hematopoietic, hepatic and renal functions including urinalysis with careful microscopic examination are recommended during therapy with sulfonamides.

      2. Therapy should be discontinued if any alteration in the hematopoietic system, a reduction in urine output, development of skin reactions, or impairment of renal or hepatic function occurs.

      3. Maintain adequate fluid intake during therapy and for 2 or 3 days thereafter in order to prevent crystalluria and stone formation.

Additional information Avoid prolonged exposure to sunlight since photosensitivity may occur.

Packaging and storage Sulfamethoxazole shall be kept in well-closed containers, protected from light.

Identification

      A. The infrared absorption spectrum is concordant with the spectrum obtained from Sulfamethoxazole RS (Appendix 2.1) or with the reference spectrum of Sulfamethoxazole.

      B. The ultraviolet absorption spectrum of a 0.001 per cent w/v solution in 1 M sodium hydroxide exhibits a maximum at 257 nm and a minimum at 224 nm; the absorbance of a 1-cm layer at 257 nm is between 0.64 and 0.69 (Appendix 2.2).

      C. Dissolve 20 mg in 0.5 ml of 2 M hydrochloric acid and add 1 ml of water: the resulting solution yields the reaction characteristic of primary aromatic amines (Appendix 5.1), giving an orange-red precipitate. 

Melting range 168º to 172º (Appendix 4.3).

Loss on drying Not more than 0.5 per cent w/w after drying at 105º for 4 hours (Appendix 4.15).

Sulfated ash Not more than 0.1 per cent w/w (Appendix 5.3).

Selenium Not more than 30 ppm (Appendix 5.2); use 200 mg.

Sulfanilamide and sulfanilic acid Not more than 0.2 per cent w/w of each. Carry out the test as described in the “Thin-layer Chromatography” (Appendix 3.1).

      Mobile phase Prepare a mixture of 25 volumes of ethanol, 25 volumes of n-heptane, 25 volumes of chloroform, and 7 volumes of glacial acetic acid.

      Modified Ehrlich’s reagent Dissolve 100 mg of 4-dimethylaminobenzaldehyde in 1 ml of hydrochloric acid and dilute with ethanol to 100 ml. Standard solution Dissolve 100 mg of Sulfamethoxazole RS in 0.10 ml of strong ammonia solution, dilute with methanol to 10.0 ml, and mix.

      Standard solution Dissolve 100 mg of Sulfamethoxazole RS in 0.10 ml of strong ammonia solution, dilute with methanol to 10.0 ml, and mix.

      Reference solution Dissolve 20 mg of Sulfanilamide RS and 20 mg of sulfanilic acid in 10 ml of strong ammonia solution, and dilute with methanol to 100.0 ml. Transfer 5.0 ml of the solution to a 50-ml volumetric flask, add 10 ml of strong ammonia solution, dilute with methanol to volume, and mix.

      Test solution Dissolve 100 mg in 0.10 ml of strong ammonia solution, dilute with methanol to 10.0 ml, and mix.

      Procedure Apply separately 10 μl each of Standard solution, Reference solution, and Test solution, to a plate coated with silica gel G. Place the plate in an unsaturated chromatographic chamber. After removal of the plate, allow it to dry in air, spray with Modified Ehrlich’s reagent, and allow the plate to stand for 15 minutes: sulfamethoxazole produces a spot at an Rf value of about 0.7, sulfanilamide at an Rf value of about 0.5, and sulfanilic acid at an Rf value of about 0.1. Any spots produced by sulfanilamide or sulfanilic acid from Test solution at the respective Rf values are not greater in size or intensity than spots produced by sulfanilamide or sulfanilic acid from Reference solution.

Assay Dissolve about 500 mg of Sulfamethoxazole, accurately weighed, in a mixture of 20 ml of glacial acetic acid and 40 ml of water, and add 15 ml of hydrochloric acid. Proceed as directed under the “Nitrite Titration” (Appendix 6.9), beginning with “Cool the solution...”. Each ml of 0.1 M sodium nitrite is equivalent to 25.33 mg of C10H11N3O3S.

MONOGRAPHS • SULFAMETHOXAZOLE
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หมายเหตุ / Note : TP II 2011 PAGE 152 - 153