Sulfamethoxazole

This article is compiled based on the United States Pharmacopeia (USP) – 2025 Edition

Issued and maintained by the United States Pharmacopeial Convention (USP)

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1 DEFINITION

Sulfamethoxazole contains NLT 98.0% and NMT 102.0% of sulfamethoxazole (C₁₀H₁₁N₃O₃S), calculated on the dried basis.

2 IDENTIFICATION

Change to read:

A. SPECTROSCOPIC IDENTIFICATION TESTS 〈197〉 , Infrared Spectroscopy: 197K or 197A (IRA 1-May-2021)

B. The retention time of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay.

3 ASSAY

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4 PROCEDURE

Buffer: 13.6 g/L of potassium dihydrogen phosphate adjusted with a 20-g/L solution of potassium hydroxide to a pH of 5.3 Mobile phase: Methanol and Buffer (30:70)

Standard solution: 0.1 mg/mL (IRA 1-May-2021) of USP Sulfamethoxazole RS (IRA 1-May-2021) in Mobile phase. Sonicate at 45° with intermittent shaking to dissolve before final dilution.

System suitability solution: 0.1 mg/mL each of USP Sulfamethoxazole RS and USP Sulfamethoxazole Related Compound A RS in Mobile phase. Sonicate at 45° with intermittent shaking to dissolve before final dilution. (IRA 1-May-2021)

Sample solution: 0.1 mg/mL of Sulfamethoxazole in Mobile phase. Sonicate at 45° with intermittent shaking to dissolve before final dilution.

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 210 nm

Column: 4-mm × 25-cm; 5-µm packing L7

Flow rate: 0.9 mL/min

Injection volume: 20 µL System suitability

Samples: System suitability solution and (IRA 1-May-2021) Standard solution

[NOTE—The relative retention times for sulfamethoxazole and sulfamethoxazole related compound A are 1.0 and 1.2, respectively.] Suitability requirements

Resolution: NLT 3.5 between sulfamethoxazole and sulfamethoxazole related compound A, System suitability solution (IRA 1-May-2021)

Relative standard deviation: NMT 0.73%, Standard solution (IRA 1-May-2021)

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of sulfamethoxazole (C₁₀H₁₁N₃O₃S) in the portion of Sulfamethoxazole taken:

Result = (r_U/r_S) × (C_S/C_U) × 100

r_U = peak response of sulfamethoxazole from the Sample solution

r_S = peak response of sulfamethoxazole from the Standard solution

C_S = concentration of USP Sulfamethoxazole RS in the Standard solution (mg/mL)

C_U = concentration of Sulfamethoxazole in the Sample solution (mg/mL)

Acceptance criteria: 98.0%–102.0% on the dried basis

5 IMPURITIES

RESIDUE ON IGNITION 〈281〉: NMT 0.1%

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ORGANIC IMPURITIES

Buffer, Mobile phase, System suitability solution, (IRA 1-May-2021) and Chromatographic system: Proceed as directed in the Assay.

(IRA 1-May-2021)

Peak identification solution: 1 µg/mL each of USP Sulfamethoxazole Related Compound A RS, USP Sulfamethoxazole Related Compound B RS, USP Sulfamethoxazole Related Compound C RS, USP Sulfanilic Acid RS, and USP Sulfanilamide RS in Mobile phase. Sonicate, if necessary, to dissolve before final dilution.

Sensitivity solution: 0.3 µg/mL of USP Sulfamethoxazole RS in Mobile phase. Sonicate, if necessary, to dissolve before final dilution. (IRA 1- May-2021)

Standard solution: 1 µg/mL each of USP Sulfamethoxazole RS and USP Sulfamethoxazole Related Compound F RS in Mobile phase. Sonicate,

if necessary, to dissolve before final dilution.

Sample solution: 1 mg/mL of Sulfamethoxazole in Mobile phase. Sonicate at 45° with intermittent shaking to dissolve before final dilution. System suitability

Samples: System suitability solution, Sensitivity solution, (IRA 1-May-2021) and Standard solution Suitability requirements

Resolution: NLT 3.5 between sulfamethoxazole and sulfamethoxazole related compound A, (IRA 1-May-2021) System suitability solution Relative standard deviation: NMT 5.0% each (IRA 1-May-2021) for sulfamethoxazole and sulfamethoxazole related compound F, (IRA 1-May-2021) Standard solution

Signal-to-noise ratio: NLT 10, Sensitivity solution (IRA 1-May-2021)

Analysis

Samples: Peak identification solution, Standard solution, and Sample solution

Calculate the percentage of sulfamethoxazole related compound F in the portion of Sulfamethoxazole taken:

Result = (r_U/r_S) × (C_S/C_U) × 100

r_U = peak response of sulfamethoxazole related compound F from the Sample solution

r_S = peak response of sulfamethoxazole related compound F from the Standard solution

C_S = concentration of USP Sulfamethoxazole Related Compound F RS in the Standard solution (mg/mL)

C_U = concentration of Sulfamethoxazole in the Sample solution (mg/mL)

Calculate the percentage of any other (IRA 1-May-2021) individual impurity in the portion of Sulfamethoxazole taken:

Result = (r_U/r_S) × (C_S/C_U) × 100

r_U = peak response of any other (IRA 1-May-2021) individual impurity from the Sample solution

r_S = peak response of sulfamethoxazole from the Standard solution

C_S = concentration of USP Sulfamethoxazole RS in the Standard solution (mg/mL)

C_U = concentration of Sulfamethoxazole in the Sample solution (mg/mL)

Acceptance criteria: See Table 1. The reporting threshold is 0.03%.

Table 1

6 SPECIFIC TESTS

LOSS ON DRYING 〈731〉

Analysis: Dry at 105° for 4 h.

Acceptance criteria: NMT 0.5%

7 ADDITIONAL REQUIREMENTS

PACKAGING AND STORAGE: Preserve in well-closed, light-resistant containers. Store at room temperature.

Change to read:

USP REFERENCE STANDARDS 〈11〉

USP Sulfamethoxazole RS

USP Sulfamethoxazole Related Compound A RS

N-{4-[N-(5-Methylisoxazol-3-yl)sulfamoyl]phenyl}acetamide. C₁₂H₁₃N₃O₄S    295.31

USP Sulfamethoxazole Related Compound B RS

4-Amino-N-{4-[N-(5-methylisoxazol-3-yl)sulfamoyl]phenyl}benzenesulfonamide.  C₁₆H₁₆N₄O₅S₂     408.45

USP Sulfamethoxazole Related Compound C RS

5-Methylisoxazol-3-amine.   C₄H₆N₂O    98.11 (IRA 1-May-2021)

USP Sulfamethoxazole Related Compound F RS

4- Amino-N-(3-methylisoxazol-5-yl)benzenesulfonamide. C₁₀H₁₁N₃O₃S    253.28

USP Sulfanilamide RS

4-    Aminobenzenesulfonamide. C₆H₈N₂O₂S    172.20

USP Sulfanilic Acid RS

4-Aminobenzenesulfonic acid.  C₆H₇NO₃S    173.19