Tiamulin

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 contains NLT 96.5% and NMT 102.0% of tiamulin (C₂₈H₄₇NO₄S), calculated on the dried basis.

2 IDENTIFICATION

A. SPECTROSCOPIC IDENTIFICATION TESTS 〈197〉 , Infrared Spectroscopy: 197A or 197K.

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

Buffer: Dissolve 10.0 g of ammonium carbonate in water, add 22 mL of perchloric acid TS, and dilute with water to 1000 mL. Adjust with ammonium hy droxide to a pH of 10.0.

Mobile phase: Methanol, acetonitrile, and Buffer (490:210:300) Diluent: Acetonitrile and Buffer (1:1)

Standard solution: 5.0 mg/mL of USP Tiamulin Fumarate RS in Diluent

Sample solution: 4.0 mg/mL of Tiamulin in Diluent

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 212 nm

Column: 4.6-mm × 15-cm; 5-µm packing L1

Flow rate: 1 mL/min

Injection volume: 20 µL

System suitability

Sample: Standard solution

Suitability requirements

Resolution: NLT 2 between tiamulin and its subsequent peak

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of tiamulin (C₂₈H₄₇NO₄S) in the portion of Tiamulin taken:

Result = (r_U/r_S) × (C_S/C_U) × (M_r1/M_r2) × 100

r_U = peak area from the Sample solution

r_S = peak area from the Standard solution

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

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

M_r1 = molecular weight of tiamulin, 493.74

M_r2 = molecular weight of tiamulin fumarate, 609.82

Acceptance criteria: 96.5%–102.0% on the dried basis

4 IMPURITIES

4.1 LIMIT OF ALCOHOL AND TOLUENE

Proceed as directed in Residual Solvents 〈467〉.

Acceptance criteria

Alcohol: NMT 1.0%

Toluene: NMT 0.08%

Sum of alcohol and toluene: NMT 1.0%

Change to read:

4.2 ORGANIC IMPURITIES

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

Toluene solution: Transfer 0.1 mL of toluene to a 100-mL volumetric flask, and dilute with acetonitrile to volume. Transfer 0.1 mL of this solution to another 100-mL volumetric flask, and dilute with Diluent to volume.

Diluted sample solution: 0.04 mg/mL of Tiamulin from the Sample solution in Diluent

Analysis

Samples: Standard solution, Sample solution, Toluene solution, and Diluted sample solution

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

Result = (r_U/r_T) × D × (ERR 1-Dec-2020) 100

r_U = peak area of each individual impurity from the Sample solution

r_T = peak area of tiamulin from the Diluted sample solution

D  = dilution factor for the Sample solution, 0.01 (ERR 1-Dec-2020)

Acceptance criteria: See Table 1. Disregard the toluene peak and any peak from the Sample solution less than 0.1 times the area of the principal peak from the Diluted sample solution.

Table 1

5 SPECIFIC TESTS

BACTERIAL ENDOTOXINS TEST 〈85〉: It contains NMT 0.4 USP Endotoxin Units/mg.

LOSS ON DRYING 〈731〉

Analysis: Dry at 80° to constant weight.

Acceptance criteria: NMT 1.0%

CLARITY AND COLOR OF SOLUTION

Sample: 2.5 g Instrumental conditions

(See Ultraviolet-Visible Spectroscopy 〈857〉.) Analytical wavelength: 420 nm

Analysis: Dissolve the Sample in methanol, and dilute with methanol to 50.0 mL.

Acceptance criteria: The solution is clear, and its absorbance is NMT 0.050.

6 ADDITIONAL REQUIREMENTS

PACKAGING AND STORAGE: Preserve in well-closed, 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 RS

USP Tiamulin Fumarate RS