Minocycline for Injection

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

Minocycline for Injection is sterile, freeze-dried Minocycline Hydrochloride suitable for parenteral use. It contains the equivalent of NLT 90.0% and NMT 120.0% of the labeled amount of minocycline (C₂₃H₂₇N₃O₇).

2 IDENTIFICATION

A. 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

3.1 Procedure

Mobile phase: Dimethylformamide, tetrahydrofuran, 0.2 M ammonium oxalate, and 0.01 M edetate disodium (120:80:600:180). Adjust with ammonium hydroxide to a pH of 7.2.

System suitability solution: Dissolve 10 mg of USP Minocycline Hydrochloride RS in 20 mL of 0.2 M ammonium oxalate. Heat on a water bath at 60° for 3 h, allow to cool, and dilute with water to 25.0 mL.

Standard solution: 0.5 mg/mL of minocycline from USP Minocycline Hydrochloride RS in water. Use this solution within 3 h.

Sample solution 1 (where it is represented as being in a single-dose container): Nominally 0.5 mg/mL of minocycline, prepared as follows. Constitute Minocycline for Injection in a volume of water, corresponding to the volume of solvent specified in the labeling. Withdraw all of the withdrawable contents, using a hypodermic needle and syringe, and dilute with water.

Sample solution 2 (where the label states the quantity of minocycline in a given volume of constituted solution): Nominally 0.5 mg/mL of minocycline, prepared as follows. Constitute Minocycline for Injection in a volume of water, corresponding to the volume of solvent specified in the labeling. Dilute a portion of constituted solution with water.

Chromatographic system

• (See Chromatography 〈621〉, System Suitability.)
• Mode: LC
• Detector: UV 280 nm
• Column: 4.6-mm × 25-cm; 5-µm packing L1
• Column temperature: 40°
• Flow rate: 1.5 mL/min
• Injection volume: 20 µL

System suitability

• Samples: System suitability solution and Standard solution
• [Note-The relative retention times for epiminocycline and minocycline are 0.7 and 1.0, respectively.]
• Suitability requirements
• Capacity factor: 5.0–11.5, Standard solution
• Resolution: NLT 4.6 between epiminocycline and minocycline, System suitability solution
• Tailing factor: 0.9–2.0 for minocycline, Standard solution
• Relative standard deviation: NMT 2.0%, Standard solution

Analysis

Samples: Standard solution, and Sample solution 1 or Sample solution 2

Calculate the percentage of the labeled amount of minocycline (C₂₃H₂₇N₃O₇) in the container, or in the portion of constituted solution taken:

Result = (rᵤ/rₛ) × (Cₛ/Cᵤ) × P × F × 100

rᵤ = peak response from Sample solution 1 or Sample solution 2

rₛ = peak response from the Standard solution

Cₛ = concentration of USP Minocycline Hydrochloride RS in the Standard solution (mg/mL)

Cᵤ = nominal concentration of Sample solution 1 or Sample solution 2 (mg/mL)

P = potency of minocycline in USP Minocycline Hydrochloride RS (µg/mg)

F = conversion factor, 0.001 mg/µg

Acceptance criteria: 90.0%–120.0%

4 PERFORMANCE TESTS

Uniformity of Dosage Units 〈905〉: Meets the requirements

5 IMPURITIES

5.1 Limit of Epiminocycline

Mobile phase, System suitability solution, Standard solution, Sample solution 1 or Sample solution 2, Chromatographic system, and System suitability: Proceed as directed in the Assay.

[Note-The relative retention times for epiminocycline and minocycline are 0.7 and 1.0, respectively.]

Analysis: Calculate the percentage of epiminocycline in the portion of Minocycline for Injection taken:

Result = (r_U/r_T) × 100

r_U = peak area of epiminocycline from Sample solution 1 or Sample solution 2

r_T = total area of all the peaks from Sample solution 1 or Sample solution 2

Acceptance criteria: NMT 6.0%

6 SPECIFIC TESTS

6.1 pH 〈791〉

Sample solution: Nominally 10 mg/mL of minocycline

Acceptance criteria: 2.0–3.5

6.2 Water Determination, Method I 〈921〉

Test preparation: Prepare as directed for a hygroscopic specimen.

Acceptance criteria: NMT 3.0%

6.3 Particulate Matter in Injections 〈788〉

Meets the requirements for small-volume injections

6.4 Sterility Tests 〈71〉

Meets the requirements

6.5 Bacterial Endotoxins Test 〈85〉

It contains NMT 1.25 USP Endotoxin Units/mg of minocycline.

6.6 Constituted Solution 

At the time of use, it meets the requirements for Injections and Implanted Drug Products 〈1〉, Specific Tests, Completeness and clarity of solutions.

6.7 Other Requirements

It meets the requirements for Labeling 〈7〉, Labels and Labeling for Injectable Products.

7 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve as described in Packaging and Storage Requirements 〈659〉, Injection Packaging, Packaging for constitution, protected from light.

USP Reference Standards 〈11〉

USP Minocycline Hydrochloride RS