Tiamulin Fumarate

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

Tiamulin Fumarate contains NLT 97.0% and NMT 102.0% of tiamulin fumarate (C₂₈H₄₇NO₄S₄ · C₄H₄O₄), calculated on the dried basis.

2 IDENTIFICATION

Change to read:

A. SPECTROSCOPIC IDENTIFICATION TESTS 〈197〉 , Infrared Spectroscopy: 197A or 197K[NOTE—When using 197K, intimately mix Tiamulin Fumarate with potassium bromide, but do not grind.] (CN 1-MAY-2020)

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

PROCEDURE

Solution A: 6% perchloric acid

Buffer: Transfer 10 g of ammonium carbonate to a 1000-mL volumetric flask, and dissolve in 800 mL of water. Add 24 mL of Solution A, and dilute with water to volume.

Mobile phase: Methanol, acetonitrile, and Buffer (49:23:28)

System suitability solution: 0.08 mg/mL of USP Tiamulin Fumarate RS and 0.08 mg/mL of USP Tiamulin Related Compound A RS in Mobile phase

Standard solution: 4 mg/mL of USP Tiamulin Fumarate RS in Mobile phase Sample solution: 4 mg/mL of Tiamulin Fumarate in Mobile phase

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 212 nm

Column: 4.6-mm × 25-cm; 5-µm packing L1

Column temperature: 30 ± 3°

Flow rate: 1.2 mL/min

Injection volume: 20 µL

System suitability

Samples: System suitability solution and Standard solution Suitability requirements

[NOTE—The tiamulin related compound A peak elutes before the tiamulin fumarate peak.]

Resolution: NLT 2.0 between tiamulin related compound A and tiamulin fumarate, System suitability solution

Tailing factor: NMT 2.0, Standard solution

Relative standard deviation: NMT 2.0%, Standard solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of tiamulin fumarate (C₂₈H₄₇NO₄S₄ · C₄H₄O₄) in the portion of Tiamulin Fumarate taken:

Result = (r_U/r_S) × (C_S/C_U) × 100

r_U = peak response from the Sample solution

r_S = peak response from the Standard solution

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

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

Acceptance criteria: 97.0%–102.0% on the dried basis

4 OTHER COMPONENTS

CONTENT OF FUMARATE

Sample solution: 450 mg of Tiamulin Fumarate in 60 mL of a mixture of alcohol and water (1:1)

Analysis: Titrate the Sample solution with 0.1 N sodium hydroxide VS, using a glass–calomel electrode (see Titrimetry 〈541〉). Perform a blank determination, and make any necessary correction. Each milliliter of 0.1 N sodium hydroxide is equivalent to 5.8 mg of fumarate.

Acceptance criteria: 83.7–87.3 mg

5 IMPURITIES

RESIDUE ON IGNITION 〈281〉: NMT 0.1%

ORGANIC IMPURITIES

Solution A, Buffer, Mobile phase, System suitability solution, Standard solution, Sample solution, Chromatographic system, and System suitability: Proceed as directed in the Assay.

Analysis

Sample: Sample solution

Calculate the area percentage of each impurity, relative to tiamulin fumarate, in the portion of Tiamulin Fumarate taken:

Result = (r_U/r_T) × 100

r_U = peak response of each impurity from the Sample solution

r_T = peak response of tiamulin fumarate from the Sample solution

Acceptance criteria: See Table 1. Disregard the peak due to fumarate at a relative retention time of 0.15.

Table 1

6 SPECIFIC TESTS

OPTICAL ROTATION 〈781S〉 , Procedures, Specific Rotation

Sample solution: 5.0 mg/mL in dioxane

Acceptance criteria: +24° to +28°, on the dried basis, measured at 20°

PH 〈791〉

Sample solution: 10 mg/mL

Acceptance criteria: 3.1–4.1

LOSS ON DRYING 〈731〉

Analysis: Dry under vacuum at 105° for 3 h. Acceptance criteria: NMT 0.5%

CLARITY AND COLOR OF SOLUTION

Sample: 5 g

Analysis: Transfer the Sample to a 100-mL volumetric flask. Dissolve in and dilute with water to volume.

Acceptance criteria: The solution is clear and colorless, and its absorbances determined in a 1-cm cell at 400 and 650 nm are NMT 0.150 and 0.030 absorbance units, respectively.

7 ADDITIONAL REQUIREMENTS

PACKAGING AND STORAGE: Preserve in tight, light-resistant containers, and store at room temperature.

LABELING: Label it to indicate that it is for veterinary use only.

USP REFERENCE STANDARDS 〈11〉

USP Tiamulin Fumarate RS

USP Tiamulin Related Compound A RS

Tosyl pleuromutilin.