Demeclocycline 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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C₂₁H₂₁ClN₂O₈ · HCl 501.31

2-Naphthacenecarboxamide, 7-chloro-4-(dimethylamino)-1,4,4a,5,5a,6,11,12a-octahydro-3,6,10,12,12a-pentahydroxy-1,11-dioxo-, monohydrochloride, 4S-(4α,4aα,5aα,6β,12aα)-;

7-Chloro-4-(dimethylamino)-1,4,4a,5,5a,6,11,12a-octahydro-3,6,10,12,12a-pentahydroxy-1,11-dioxo-2-naphthacenecarboxamide monohydrochloride  CAS RN®: 64-73-3; UNII: 29O079NTYT.

1 DEFINITION

Demeclocycline Hydrochloride has a potency of NLT 900 µg/mg of demeclocycline hydrochloride (C₂₁H₂₁ClN₂O₈ · HCl), calculated on the dried basis.

2 IDENTIFICATION

Change to read:

A. Spectroscopic Identification Tests 〈197〉, Infrared Spectroscopy: 〈197K〉 or 〈197A〉

Change to read:

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

Change to read:

3.1 Procedure

Solution A: Mix appropriate volumes of 0.2 M dibasic potassium phosphate and 0.2 M monobasic potassium phosphate to prepare a buffer with a pH of 9.0.

Solution B: 0.02 M tetrabutylammonium hydrogen sulfate. Adjust with sodium hydroxide TS to a pH of 9.0.

Solution C: 0.01 M edetate disodium. Adjust with sodium hydroxide TS to a pH of 9.0.

Mobile phase: Transfer 80 g of tertiary butyl alcohol to a 1000-mL volumetric flask with the aid of 200 mL of water. Add 100 mL of Solution A, 150 mL of Solution B, and 100 mL of Solution C. Dilute with water to volume. 

Diluent: 0.01 N hydrochloric acid

System suitability solution: 1 mg/mL of USP Demeclocycline Hydrochloride RS in Diluent. Allow to stand for 3 h.

Standard solution: 1 mg/mL of USP Demeclocycline Hydrochloride RS in Diluent

Sample solution: 1 mg/mL of Demeclocycline Hydrochloride in Diluent

Chromatographic system

• (See Chromatography 〈621〉, System Suitability.)
• Mode: LC
• Detector: UV 254 nm
• Column: 4.6-mm × 25-cm; 8-µm packing L21
• Column temperature: 60 ± 0.5°
• Flow rate: 1 mL/min
• Injection volume: 20 µL

System suitability

• Samples: System suitability solution and Standard solution
• [Note-The relative retention times for epidemethylchlortetracycline and demeclocycline are 0.7 and 1.0, respectively.]
• Suitability requirements
• Resolution: NLT 3.0 between the epidemethylchlortetracycline peak and the demeclocycline peak, System suitability solution
• Relative standard deviation: NMT 2.0%, Standard solution

Analysis

Samples: Standard solution and Sample solution

Calculate the quantity, in µg/mg, of demeclocycline hydrochloride (C₂₁H₂₁ClN₂O₈ · HCl) in the portion of Demeclocycline Hydrochloride taken:

Result = (r_u/r_s) × (C_s/C_u) × P

r_u = peak response of demeclocycline from the Sample solution

r_s = peak response of demeclocycline from the Standard solution

C_s = concentration of USP Demeclocycline Hydrochloride RS in the Standard solution (mg/mL)

C_u = concentration of Demeclocycline Hydrochloride in the Sample solution (mg/mL)

P = potency of demeclocycline hydrochloride in USP Demeclocycline Hydrochloride RS (µg/mg)

Acceptance criteria: NLT 900 µg/mg on the dried basis

4 SPECIFIC TESTS

4.1 Crystallinity 〈695〉: Meets the requirements

4.2 pH 〈791〉

Sample solution: 10 mg/mL

Acceptance criteria: 2.0–3.0

Change to read:

4.3 Loss on Drying 〈731〉

Sample: 100 mg

Analysis: Dry the Sample in a capillary-stoppered bottle in vacuum at 60° for 3 h.

Acceptance criteria: NMT 2.0%

5 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in tight, light-resistant containers.

USP Reference Standards 〈11〉

USP Demeclocycline Hydrochloride RS