Clonidine Hydrochloride 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

Clonidine Hydrochloride Injection is a sterile solution of Clonidine Hydrochloride in Water for Injection. It contains NLT 90.0% and NMT 110.0% of the labeled amount of clonidine hydrochloride (C₉H₉Cl₂N₃ · HCl).

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.

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

Diluent: 9 g/L of sodium chloride in water

Standard solution: 0.1 mg/mL of USP Clonidine Hydrochloride RS in Diluent. Sonicate to dissolve, if needed.

Sample solution: Nominally 0.1 mg/mL of clonidine hydrochloride from Injection. Dilute with Diluent, if needed.

Acceptance criteria: The UV spectrum of the Sample solution exhibits maxima and minima at the same wavelengths as that of the Standard solution.

3 ASSAY

3.1 PROCEDURE

Solution A: Dilute 2.0 mL of perchloric acid (70%), in 4000 mL of water.

Solution B: Acetonitrile and methanol (95:5)

Mobile phase: Solution A and Solution B (85:15)

Diluent: 9 g/L of sodium chloride in water

Standard solution: 0.01 mg/mL of USP Clonidine Hydrochloride RS in Diluent. Sonicate to dissolve, if needed.

Sample solution: Nominally 0.01 mg/mL of clonidine hydrochloride from the Injection, diluted with Diluent

3.1.1 Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 210 nm

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

Flow rate: 1.2 mL/min

Injection volume: 25 µL

Run time: NLT 2 times the retention time of clonidine

3.1.2 System suitability

Sample: Standard solution

3.1.3 Suitability requirements

Tailing factor: NMT 1.5

Relative standard deviation: NMT 1.0%

3.1.4 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of clonidine hydrochloride (C₉H₉Cl₂N₃ · HCl) in the portion of Injection taken:

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

r_U = peak response of clonidine from the Sample solution U

r_S = peak response of clonidine from the Standard solution 5

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

C_U = nominal concentration of clonidine hydrochloride in the Sample solution (mg/mL)

Acceptance criteria: 90.0%-110.0%

4 IMPURITIES

4.1 ORGANIC IMPURITIES

Solution A, Solution B, and Diluent: Prepare as directed in the Assay.

Mobile phase: See Table 1.

   Table 1

Sensitivity solution: 0.05 µg/mL of USP Clonidine Hydrochloride RS in Diluent

Standard solution: 0.5 µg/mL of USP Clonidine Hydrochloride RS in Diluent. Sonicate to dissolve, if needed.

Sample solution: Nominally 100 µg/mL of clonidine hydrochloride from the Injection. Dilute with Diluent, if needed.

Chromatographic system: Proceed as directed in the Assay, except for the Flow rate and the Run time.

Flow rate: 1 mL/min

Run time: 60 min

4.1.1 System suitability

Samples: Sensitivity solution and Standard solution

4.1.2 Suitability requirements

Relative standard deviation: NMT 10.0%, Standard solution

Signal-to-noise ratio: NLT 10, Sensitivity solution

4.1.3 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of any unspecified impurity in the portion of Injection taken:

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

r_U = peak response of any unspecified impurity from the Sample solution

r_S = peak response of clonidine from the Standard solution S

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

C_U = nominal concentration of clonidine hydrochloride in the Sample solution (µg/mL)

Acceptance criteria: See Table 2.

   Table 2

^a Process impurity for peak identification only; not to be reported or included in the total impurities.

5 SPECIFIC TESTS

PH (791): 5.0-7.0

PARTICULATE MATTER IN INJECTIONS (788): Meets the requirements for small-volume injections

Change to read:

OSMOLALITY AND OSMOLARITY (785)

Osmolality: _{▲(Official 1-Aug-2022)} 270-330 mOsmol/kg

STERILITY TESTS (71): Meets the requirements

BACTERIAL ENDOTOXINS TEST (85): Meets the requirements

6 ADDITIONAL REQUIREMENTS

PACKAGING AND STORAGE: Preserve in well-closed Type 1 glass vials. Store at controlled room temperature.

USP REFERENCE STANDARDS (11)

USP Clonidine Hydrochloride RS