Clonidine

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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C₉H₉CI₂N₃          230.09

Benzenamine, 2,6-dichloro-N-2-imidazolidinylidene-;

2-[(2,6-Dichlorophenyl)imino]imidazolidine CAS RN^®: 4205-90-7; UNII: MN3L5RMN02.

1 DEFINITION

Clonidine contains NLT 99.0% and NMT 101.0% of clonidine (C₉H₉CI₂N₃), calculated on the dried basis.

2 IDENTIFICATION

A. SPECTROSCOPIC IDENTIFICATION TESTS (197), Infrared Spectroscopy: 197K

B. SPECTROSCOPIC IDENTIFICATION TESTS (197), Ultraviolet-Visible Spectroscopy: 1970

Medium: 0.01 N hydrochloric acid

Sample solution: 0.3 mg/mL of Clonidine in Medium

Acceptance criteria: Absorptivities are about 2.1 and 1.8 for the maxima at 271 nm and 279 nm, respectively, calculated on the dried basis.

3 ASSAY

3.1 PROCEDURE

Sample solution: 190 mg of Clonidine in 100 mL of glacial acetic acid

Analysis: Titrate with 0.1 N perchloric acid VS, using a silver-silver chloride glass combination electrode with liquid junction. Perform a blank determination, and make any necessary correction (see Titrimetry (541)). Each mL of 0.1 N perchloric acid is equivalent to 23.01 mg of clonidine (C₉H₉CI₂N₃).

Acceptance criteria: 99.0%-101.0% on the dried basis

4 IMPURITIES

4.1 RESIDUE ON IGNITION (281)

Analysis: Ignite at 500 ± 25° to constant weight.

Acceptance criteria: NMT 0.1%

4.2 ORGANIC IMPURITIES

1 M phosphoric acid: 115 g/L of phosphoric acid in water

Buffer: 4 g/L of monobasic potassium phosphate in water. Adjust with 1 M phosphoric acid to a pH of 4.0.

Solution A: Acetonitrile and Buffer (75:25)

Mobile phase: See Table 1.

   Table 1

Acetylclonidine solution: 0.05 mg/mL of USP Clonidine Related Compound A RS, prepared as follows. Initially dissolve USP Clonidine Related Compound A RS in acetonitrile (1 mg/mL), and dilute with Buffer to volume.

System suitability solution: 0.86 mg/mL of USP Clonidine RS and 0.86 µg/mL of clonidine related compound A from Acetylclonidine solution in Buffer

Standard solution: 8.6 µg/mL of USP Clonidine RS in Buffer

Sample solution: 0.86 mg/mL of Clonidine in Buffer

Blank: Buffer

4.2.1 Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 210 nm

Column: 3.0-mm x 15-cm; 5-µm packing L56

Column temperature: 40°

Flow rate: 1.5 mL/min

Injection volume: 5 µL

4.2.2 System suitability

Samples: System suitability solution and Standard solution

4.2.3 Suitability requirements

Resolution: NLT 5 between clonidine and acetylclonidine, System suitability solution

Tailing factor: NMT 2.5 for clonidine, System suitability solution

Relative standard deviation: NMT 5%, Standard solution

4.2.4 Analysis

Samples: Standard solution, Sample solution, and Blank

Calculate the percentage of each impurity in the portion of Clonidine taken:

                 Result = (r_U/r_S) x (C_S/C_U) × 100

r_U = peak response for each impurity from the Sample solution

r_S = peak response of clonidine from the Standard solution s

C_S = concentration of the Standard solution (µg/mL)

C_U = concentration of the Sample solution (µg/mL)

4.2.5 Acceptance criteria

Individual impurity: NMT 0.1%

Total impurities: NMT 0.2%

5 SPECIFIC TESTS

5.1 LOSS ON DRYING (731).

Analysis: Dry a sample at 60° under vacuum to constant weight.

Acceptance criteria: NMT 0.5%

5.2 APPEARANCE OF SOLUTION

5.2.1 Color of solution

Standard solution: 4.8 µg/mL of potassium chromate in water

Sample solution: 100 mg/mL in methanol

Acceptance criteria: The color of 10 mL of Sample solution is not more intense than that of 10 mL of Standard solution when compared in matched color-comparison tubes (see Visual Comparison (630)).

5.2.2 Turbidity

Sample solution: Prepare as directed in Color of solution.

Acceptance criteria: 10 mL of Sample solution has no more turbidity than 10 mL of methanol when compared in matched color-comparison tubes (see Visual Comparison 〈630〉).

6 ADDITIONAL REQUIREMENTS

PACKAGING AND STORAGE: Preserve in tight containers, and store at room temperature.

Change to read:

USP REFERENCE STANDARDS (11)

USP Clonidine RS

USP Clonidine. Related Compound A RS

1-Acetyl-2-(2,6-^▲dichlorophenylimino)imidazolidine _{▲(ERR 1-Mar-2021)}

C₁₁H₁₁CI₂N₃O          272.13