Erythromycin Ethylsuccinate and Sulsoxazole Acetyl for Oral Suspension

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

Erythromycin Ethylsuccinate and Sulfisoxazole Acetyl for Oral Suspension is a dry mixture of Erythromycin Ethylsuccinate and Sulfisoxazole Acetyl with one or more suitable buffers, colors, flavors, surfactants, and suspending agents. It contains the equivalent of NLT 90.0% and NMT 120.0% of the labeled amount of erythromycin (C₃₇H₆₇NO₁₃) and the equivalent of NLT 90.0% and NMT 115.0% of the labeled amount of sulfisoxazole (C₁₁H₁₃N₃O₃S).

[NOTE-Where Erythromycin Ethylsuccinate and Sulfisoxazole Acetyl for Oral Suspension is prescribed, without reference to the quantity of erythromycin or sulfisoxazole contained therein, a product containing 40 mg/mL of erythromycin and 120 mg/mL of sulfisoxazole when constituted as directed in the labeling shall be dispensed.]

2 IDENTIFICATION

Change to read:

A _{(USP 1-MAY-2019)} THIN-LAYER CHROMATOGRAPHIC IDENTIFICATION TEST

Standard solution A: 3 mg/mL of USP Erythromycin Ethylsuccinate RS in methanol

Standard solution B: 8.7 mg/mL of USP Sulfisoxazole Acetyl RS in methanol

Sample solution: Nominally 2.5 mg/mL of erythromycin from Erythromycin Ethylsuccinate and Sulfisoxazole Acetyl for Oral Suspension in methanol. Shake this mixture by mechanical means for about 30 min. Centrifuge a portion of this mixture, and use the clear supernatant.

Chromatographic system

(See Chromatography (621), General Procedures, Thin-Layer Chromatography.)

Mode: TLC

Adsorbent: 0.25-mm layer of chromatographic silica gel mixture

Application volume: 10 µL

Developing solvent system: Methanol and chloroform (85:15)

Spray reagent: Dehydrated alcohol, p-methoxybenzaldehyde, and sulfuric acid (90:5:5)

Analysis

Samples: Standard solution A, Standard solution B, and Sample solution

Place the plate in an unlined chromatographic chamber, and develop the plate in the Developing solvent system until the solvent front has moved about 9 cm. Remove the plate from the chamber, mark the solvent front, and allow the solvent to evaporate. Spray the plate with Spray reagent. Heat the plate at 100° for 10 min, and examine the chromatograms, in which the erythromycin and succinic acid moieties appear as black-to-purple spots and the sulfisoxazole acetyl appears as a yellow spot.

Acceptance criteria: The R values of the principal black-to-purple spots of the Sample solution correspond to those of Standard solution A;

and the R, value of the principal yellow spot of the Sample solution corresponds to that of Standard solution B.

3 ASSAY

3.1 ERYTHROMYCIN

(See Antibiotics-Microbial Assays (81).)

Sample stock solution: Constitute Erythromycin Ethylsuccinate and Sulfisoxazole Acetyl for Oral Suspension as directed in the labeling, and allow to stand for 1 h. Gently shake the suspension, transfer 5.0 mL to a high-speed blender jar containing 195.0 mL of methanol, and blend for 4 ± 1 min.

Sample solution: Dilute the Sample stock solution quantitatively with Buffer B.3 to obtain a Sample solution having a concentration assumed to be equal to the median dose level of the Standard (1.0 µg/mL of erythromycin).

Analysis: Proceed as directed in Antibiotics-Microbial Assays (81).

Acceptance criteria: 90.0%-120.0%

Change to read:

3.2 SULFISOXAZOLE

Mobile phase: Acetonitrile and water (40:60) _{(USP 1-May-2019)}

Internal standard solution: 0.33 mg/mL of benzanilide in acetonitrile _{(USP 1-May-2019)}

Standard solution: 1 mg/mL of USP Sulfisoxazole Acetyl RS in Internal standard solution

Sample stock solution: Constitute Erythromycin Ethylsuccinate and Sulfisoxazole Acetyl for Oral Suspension as directed in the labeling, and allow to stand for 1 h. Gently shake Erythromycin Ethylsuccinate and Sulfisoxazole Acetyl for Oral Suspension, transfer a volume equivalent to 600 mg of sulfisoxazole to a 125-mL separator, and extract with three 75-mL portions of chloroform. Collect the extracts in a 250-mL volumetric flask and dilute with chloroform to volume. Pass a portion of this solution through a suitable filter of 1-µm or finer pore size.

Sample solution: Pipet 4 mL of the filtrate from the Sample stock solution into a glass-stoppered, 25-mL conical flask, and evaporate with the aid of a current of dry air to dryness. Add 10.0 mL of Internal standard solution, and mix.

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 254 nm

Column: 4-mm x 30-cm; 5-µm _{(USP 1-May-2019)} packing L1

Flow rate: 1.2 mL/min

Injection volume: 5 µL

System suitability

Sample: Standard solution

Suitability requirements

Resolution: NLT 3.0 between sulfisoxazole acetyl and benzanilide

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of sulfisoxazole (C₁₁H₁₃N₃O₃S) in the portion of Erythromycin Ethylsuccinate and Sulfisoxazole Acetyl for Oral Suspension taken:

Result = (R_u /R_s ) × (C_s /C_u ) × (M_r1 /M_r2 ) × 100

R_u = peak response ratio of sulsoxazole acetyl to benzanilide from the Sample solution

R_s = peak response ratio of sulsoxazole acetyl to benzanilide from the Standard solution

C_s = concentration of USP Sulsoxazole Acetyl RS in the Standard solution (mg/mL)

C_u = nominal concentration of the Sample solution (mg/mL)

M_r1 = molecular weight of sulsoxazole, 267.31

M_r2 = molecular weight of sulsoxazole acetyl, 309.35

Acceptance criteria: 90.0%–115.0%

4 PERFORMANCE TESTS

UNIFORMITY OF DOSAGE UNITS (905), Content Uniformity.

For solids packaged in single-unit containers: Meets the requirements with respect to erythromycin and sulfisoxazole

DELIVERABLE VOLUME (698): Meets the requirements

5 SPECIFIC TESTS

PH (791)

Sample solution: Suspension constituted as directed in the labeling

Acceptance criteria: 5.0-7.2

LOSS ON DRYING (731)

Analysis: Dry about 100 mg in a capillary-stoppered bottle under vacuum at 60° for 3 h.

Acceptance criteria: NMT 1.0%

6 ADDITIONAL REQUIREMENTS

PACKAGING AND STORAGE: Preserve in tight containers.

USP REFERENCE STANDARDS (11)

USP Erythromycin RS

USP Erythromycin Ethylsuccinate RS

USP Sulfisoxazole Acetyl RS