Tetracycline Hydrochloride Tablets

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

Tetracycline Hydrochloride Tablets contain NLT 90.0% and NMT 125.0% of the labeled amount of tetracycline hydrochloride (C₂₂H₂₄N₂O₈ · HCl).

2 IDENTIFICATION

Change to read:

A. (USP 1-AUG-2023) The retention time of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay.

Add the following:

B. The UV spectrum of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay. (USP 1- Aug-2023)

3 ASSAY

Change to read:

PROCEDURE

Diluent: Dimethylformamide and 0.1 M ammonium oxalate (27:68)

Mobile phase: Dimethylformamide, 0.1 M ammonium oxalate, and 0.2 M ammonium phosphate, dibasic (27:68:5). If necessary, adjust with 3 N ammonium hy droxide or 3 N phosphoric acid to a pH of 7.6–7.7.

System suitability solution: 100 μg/mL of USP Tetracycline Hydrochloride RS and 25 μg/mL of USP 4-Epianhydrotetracycline Hydrochloride RS in Diluent

Standard solution: 0.5 mg/mL of USP Tetracycline Hydrochloride RS in Diluent (USP 1-Aug-2023)

Sample solution: Nominally 0.5 mg/mL of tetracycline hydrochloride prepared as follows. Transfer a portion of finely powdered Tablets (NLT 20), equivalent to 50 mg of tetracycline hydrochloride, to a 100-mL volumetric flask. Add about 50 mL of Diluent, and sonicate for 5 min. Allow to cool, and dilute with Diluent to volume.

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 280 nm. For Identification B, use a diode array detector in the range of 200–400 nm.

Columns

Guard: 4.6-mm × 3-cm; 10-μm packing L7

Analytical: 4.6-mm × 25-cm; 5- to 10-μm packing L7

Flow rate: 2 mL/min

Injection volume: 20 μL

System suitability

Samples: System suitability solution and Standard solution

[NOTE—The relative retention times for 4-epianhydrotetracycline and tetracycline are about 0.9 and 1.0, respectively.]

Suitability requirements

Resolution: NLT 1.2 between 4-epianhydrotetracycline and tetracycline, System suitability solution

Relative standard deviation: NMT 1.0%, Standard solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of tetracycline hydrochloride (C₂₂H₂₄N₂O₈ · HCl) in the portion of Tablets taken:

Result = (r_U/r_S) × (C_S/C_U) × P × F × 100

r_U = peak response of tetracycline from the Sample solution

r_S = peak response of tetracycline from the Standard solution

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

C_U = nominal concentration of tetracycline hydrochloride in the Sample solution (mg/mL)

P = potency of USP Tetracycline Hydrochloride RS (µg/mg)

F = conversion factor, 0.001 mg/μg (USP 1-Aug-2023)

Acceptance criteria: 90.0%–125.0%

4 PERFORMANCE TESTS

Change to read:

DISSOLUTION 〈711〉

Medium: Water; 900 mL

Apparatus 2: 75 rpm. [NOTE—Maintain a distance of 45 ± 5 mm between the blade and the inside bottom of the vessel.]

Time: 60 min

Standard solution: A known concentration of USP Tetracycline Hydrochloride RS in Medium

Sample solution: Pass a portion of the solution under test through a suitable filter. Dilute with Medium, if necessary. Instrumental conditions

Mode: UV

Analytical wavelength: 276 nm

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of tetracycline hydrochloride (C₂₂H₂₄N₂O₈ · HCl) dissolved:

Result = (A_U/A_S) × C_S × (1/L) × V × D × 100

A_U = absorbance of the Sample solution

A_S = absorbance of the Standard solution

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

L = label claim (mg/Tablet)

V = volume of Medium, 900 mL

D = dilution factor for the Sample solution, if applicable (USP 1-Aug-2023)

Tolerances: NLT 80% (Q ) of the labeled amount of tetracycline hydrochloride (C₂₂H₂₄N₂O₈ · HCl) is dissolved.

UNIFORMITY OF DOSAGE UNITS 〈905〉: Meet the requirements

5 IMPURITIES

LIMIT OF 4-EPIANHYDROTETRACYCLINE

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

Standard solution: 0.015 mg/mL of USP 4-Epianhy drotetracy cline Hy drochloride RS in Diluent

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of 4-epianhydrotetracycline hydrochloride in the portion of Tablets taken:

Result = (r_U/r_S) × (C_S/C_U) × 100

r_U = peak response of 4-epianhydrotetracycline from the Sample solution

r_S = peak response of 4-epianhydrotetracycline from the Standard solution

C_S = concentration of USP 4-Epianhydrotetracycline Hydrochloride RS in the Standard solution (mg/mL)

C_U = nominal concentration of tetracycline hydrochloride in the Sample solution (mg/mL)

Acceptance criteria: NMT 3.0%

6 SPECIFIC TESTS

LOSS ON DRYING 〈731〉

Sample: About 100 mg, accurately weighed

Analysis: Dry the Sample under a vacuum at a pressure not exceeding 5 mm of mercury at 60° for 3 h. Acceptance criteria: NMT 3.0%

7 ADDITIONAL REQUIREMENTS

PACKAGING AND STORAGE: Preserve in tight, light-resistant containers.

Change to read:

USP REFERENCE STANDARDS 〈11〉

USP 4-Epianhydrotetracycline Hydrochloride RS

(4R,4aS,12aS)-4-(Dimethylamino)-3,10,11,12a-tetrahydroxy-6-methyl-1,12-dioxo-1,4,4a,5,12,12a-hexahydrotetracene-2-carboxamide hydrochloride.

C₂₂H₂₂N₂O₇ · HCl    462.88 (USP 1-Aug-2023)

USP Tetracycline Hydrochloride RS