Minocycline Hydrochloride

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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C₂₃H₂₇N₃O₇ · HCl                   493.94

2-Naphthacenecarboxamide, 4,7-bis(dimethylamino)-1,4,4a,5,5a,6,11,12a-octahydro-3,10,12,12a-tetrahydroxy-1,11dioxo-, monohydrochloride,

[4S-(4α,4aα,5aα,12aα)]-;4,7-Bis(dimethylamino)-1,4,4a,5,5a,6,11,12a-octahydro-3,10,12,12a-tetrahydroxy-1,11-dioxo-2-naphthacenecarboxamide monohydrochloride

CAS RN: 13614-98-7; UNII: 0020414E5U.

1 DEFINITION

Minocycline Hydrochloride contains the equivalent of NLT 890 µg and NMT 950 µg of minocycline (C₂₃H₂₇N₃O₇) per mg, calculated on the anhydrous basis.

2 IDENTIFICATION

Change to read:

A. SPECTROSCOPIC IDENTIFICATION TESTS (197), Infrared Spectroscopy: 197K. _{(CN 1-May-2020)} Dry the Standard and Sample at 100° for 2 h before use.

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

[NOTE-Protect the Standard solution and Sample solution from light, store in a refrigerator, and use within 3 h.]

Mobile phase: Dimethylformamide, tetrahydrofuran, 0.2 M ammonium oxalate, and 0.01 M edetate disodium TS (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: Equivalent to 500 µg/mL of minocycline (C₂₃H₂₇N₃O₇) from USP Minocycline Hydrochloride RS in water

Sample solution: Equivalent to 500 µg/mL of minocycline (C₂₃H₂₇N₃O₇) from Minocycline Hydrochloride in water

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 280 nm

Column: 4.6-mm x 25-cm; 5-µm packing 11

Column temperature: 40^o

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

Resolution: NLT 4.6 between epiminocycline and minocycline, System suitability solution

Tailing factor: 0.9-2.0, Standard solution

Relative standard deviation: NMT 2.0%, Standard solution

Analysis

Samples: Standard solution and Sample solution

Calculate the quantity, in µg/mg, of minocycline (C₂₃H₂₇N₃O₇) in the portion of Minocycline Hydrochloride taken:

Result = (r_u /r_s ) × (C_s /C_u ) × P

r_u = peak response from the Sample solution

r_s = peak response from the Standard solution

C_s = concentration of minocycline in the Standard solution (µg/mL)

C_u = concentration of minocycline in the Sample solution (µg/mL)

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

Acceptance criteria: 890–950 µg/mg on the anhydrous basis

4 IMPURITIES

RESIDUE ON IGNITION (281): NMT 0.15%

ORGANIC IMPURITIES

Mobile phase, System suitability solution, Standard solution, Chromatographic system, and System suitability: Proceed as directed in the

Assay.

[NOTE-Protect the Standard solution and the Sample solutions from light, store in a refrigerator, and use within 3 h.]

Sample solution 1: 0.25 mg/ml of Minocycline Hydrochloride in water

Sample solution 2: 5 µg/mL of Minocycline Hydrochloride in water

Sample solution 3: 3 µg/mL of Minocycline Hydrochloride in water

Run time: 2.6 times the retention time of minocycline, Sample solution 1

Analysis

Samples: Sample solution 1, Sample solution 2, and Sample solution 3

Calculate the percentage of epiminocycline in the portion of Minocycline Hydrochloride taken:

Result = (r_e1 /r_m3 ) × D₁ × 100

r_e1 = peak response of epiminocycline from Sample solution 1

r_m3 = peak response of minocycline from Sample solution 3

D₁ = dilution factor for Sample solution 3

Calculate the total percentage of impurities other than epiminocycline in the portion of Minocycline Hydrochloride taken:

Result = (r_T /r_m2 ) × D₂ × 100

r_T = sum of the peak responses of all impurities other than epiminocycline from Sample solution 1

r_m2 = peak response of minocycline from Sample solution 2

D₂ = dilution factor for Sample solution 2

Acceptance criteria

Individual impurities: NMT 1.2% epiminocycline

Total impurities (excluding epiminocycline): NMT 2.0%

5 SPECIFIC TESTS

CRYSTALLINITY (695): Meets the requirements

PH (791)

Sample: 10 mg/mL of minocycline in solution

Acceptance criteria: 3.5-4.5

WATER DETERMINATION (921), Method /: 4.3%-8.0%

STERILITY TESTS (71): Where the label states that Minocycline Hydrochloride is sterile, it meets the requirements.

BACTERIAL ENDOTOXINS TEST (85): Where the label states that Minocycline Hydrochloride is sterile or must be subjected to further processing during the preparation of injectable dosage forms, it contains NMT 1.25 USP Endotoxin Units/mg of minocycline.

6 ADDITIONAL REQUIREMENTS

PACKAGING AND STORAGE: Preserve in tight containers, protected from light.

LABELING: Where it is intended for use in preparing injectable dosage forms, the label states that it is sterile or must be subjected to further processing during the preparation of injectable dosage forms.

USP REFERENCE STANDARDS (11)

USP Minocycline Hydrochloride RS