Clonidine Hydrochloride

This article is compiled based on the United States Pharmacopeia (USP) – 2025 Edition

Issued and maintained by the United States Pharmacopeial Convention (USP)

DOWNLOAD PDF HERE

C₉H₉Cl₂N₃ · HCl        266.55

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

2-[(2,6-Dichlorophenyl)imino]imidazolidine monohydrochloride CAS RN^®: 4205-91-8; UNII: W7616XXF06.

1 DEFINITION

Change to read:

Clonidine Hydrochloride contains NLT ^▲98.0%_{▲(USP 1-May-2020)} and NMT ^▲102.0%_{▲ (USP 1-May-2020)} of clonidine hydrochloride (C₉H₉Cl₂N₃ · HCl), calculated on the dried basis.

2 IDENTIFICATION

Change to read:

A. ^▲SPECTROSCOPIC IDENTIFICATION TESTS (197), Infrared Spectroscopy: 197A or 197K, _{▲(CN 1-May-2020)}

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 _{▲(USP 1-May-2020)}

C. IDENTIFICATION TESTS GENERAL (191), Chemical Identification Tests. Chloride: Meets the requirements

3 ASSAY

Change to read:

3.1 PROCEDURE

Solution A: 1.0 mL/L of triethylamine in water

Mobile phase: Acetonitrile and Solution A (32:68). Adjust with phosphoric acid to a pH of 6.9.

(USP 1-May-2020)

Standard solution: 0.05 mg/mL of USP Clonidine Hydrochloride RS in Mobile phase ^▲_{▲(USP 1-May-2020)}

Sample solution: 0.05 mg/mL of Clonidine Hydrochloride in Mobile phase ^▲_{▲(USP 1-May-2020)}

3.2 Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 220 nm

Column: 3.9-mm x 30-cm; 10-µm packing 11

Flow rate: 2 mL/min

Injection volume: 50 µL

Run time: NLT 3 times the retention time of clonidine ^▲_{▲(USP 1-May-2020)}

3.3 System suitability

Sample: ^▲_{▲(USP 1-May-2020)} Standard solution

3.4 Suitability requirements

(USP 1-May-2020)

Tailing factor: NMT 2.0

Relative standard deviation: NMT ^▲0.73% _{▲(USP 1-May-2020)}

3.5 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of clonidine hydrochloride (C₂H₂CIN, HCI) in the portion of Clonidine Hydrochloride taken:

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

r_U = peak response of clonidine from the Sample solution

r_S = peak response of clonidine from the Standard solution

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

C_U = concentration of Clonidine Hydrochloride in the Sample solution (mg/mL)

Acceptance criteria: ^▲98.0%-102.0% _{▲(USP 1-May-2020)} on the dried basis

4 IMPURITIES

RESIDUE ON IGNITION (281): NMT 0.1%

Change to read:

4.1 ORGANIC IMPURITIES

Solution A and Mobile phase: Prepare as directed in the Assay.

Standard stock solution: 0.06 mg/mL each of USP Clonidine Hydrochloride RS, USP Clonidine Related Compound A RS, and 2.6-dichloroaniline in acetonitrile ^▲_{▲(USP 1-May-2020)}

Standard solution: 0.6 µg/mL each of USP Clonidine Hydrochloride RS. ^▲USP Clonidine Related Compound A RS, and 2.6-dichloroaniline _{▲(USP 1-May-2020)} in Mobile phase from the Standard stock solution

^▲Sensitivity solution: 0.06 µg/mL each of USP Clonidine Hydrochloride RS, USP Clonidine Related Compound A RS, and 2.6-dichloroaniline in Mobile phase from the Standard solution

Sample stock solution: 1.5 mg/mL of Clonidine Hydrochloride in Mobile phase prepared as follows. Transfer 150 mg of Clonidine Hydrochloride to a 100-mL volumetric flask. Add Mobile phase to about 60% of the volume of the flask, sonicate for 5 min, and then dilute with Mobile phase to volume._{▲ (USP 1-May-2020)}

Sample solution: 150 µg/mL of Clonidine Hydrochloride in Mobile phase from the Sample stock solution _{▲(USP 1-May-2020)}

Chromatographic system: Proceed as directed in the Assay, except for the Run time. _{▲(USP 1-May-2020)}

Run time: ^▲NLT 6A _{▲(USP 1-May-2020)} times the retention time of clonidine

4.2 System suitability

Samples: Standard solution ^▲ and. Sensitivity solution

[NOTE-See Table 1 for the relative retention times.) _{▲(USP 1-May-2020)}

4.3 Suitability requirements

Resolution: NLT 2.0 between clonidine related compound A and 2,6-dichloroaniline, Standard solution _{▲(USP 1-May-2020)}

Relative standard deviation: NMT 5% for clonidine, clonidine related compound A, and 2,6-dichloroaniline, _{▲(USP 1-May-2020)} Standard solution

Signal-to-noise ratio: NLT 10 for clonidine, clonidine related compound A, and 2,6-dichloroaniline, Sensitivity solution _{▲(USP 1-May-2020)}

4.4 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of clonidine related compound A and 2,6-dichloroaniline in the portion of Clonidine Hydrochloride taken:

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

r_U = peak response of clonidine related compound A or 2,6-dichloroaniline from the Sample solution

r_S = peak response of clonidine related compound A or 2,6-dichloroaniline from the Standard solution

C_S = concentration of USP Clonidine. Related Compound A RS or 2,6-dichloroaniline in the Standard solution (µg/mL) _{▲(USP 1-May-2020)}

C_U = concentration of Clonidine Hydrochloride in the Sample solution ^▲(µg/mL)_{▲(USP 1-May-2020)}

Calculate the percentage of any ^▲_{▲(USP 1-May-2020)} unspecified impurity in the portion of Clonidine Hydrochloride taken:

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

r_U = peak response of any (USP 1-May-2020) unspecified impurity from the Sample solution

r_S = peak response of clonidine from the Standard solution

C_S = concentration of USP Clonidine Hydrochloride RS in the Standard solution (µg/mL) (_{▲(USP 1-May-2020)}

C_U = concentration of Clonidine Hydrochloride in the Sample solution ^▲(µg/mL)_{▲(USP 1-May-2020)}

Acceptance criteria: See Table 1. The reporting threshold is ^▲(µg/mL)_{▲(USP 1-May-2020)}

Table 1

(USP 1-May-2020)

5 SPECIFIC TESTS

5.1 PH (791)

Sample solution: 50 mg/mL

Acceptance criteria: 3.5-5.5

5.2 LOSS ON DRYING (731)

Analysis: Dry at 105° to constant weight.

Acceptance criteria: NMT 0.5%

6 ADDITIONAL REQUIREMENTS

PACKAGING AND STORAGE: Preserve in tight containers. Store at controlled room temperature.

USP REFERENCE STANDARDS (11)

USP Clonidine Hydrochloride RS

USP Clonidine Related Compound A RS

1-Acetyl-2-(2,6-dichlorophenylimino)-imidazolidine).

C₁₁H₁₁CI₂N₃O        272.13