Clonidine Hydrochloride Tablets

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 Tablets contain 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.

Change to read:

B. THIN-LAYER CHROMATOGRAPHY

Standard solution: 10 mg/mL of USP Clonidine Hydrochloride RS in methanol

Sample solution: ▲Nominally 10 mg/mL of clonidine hydrochloride prepared as follows. ▲(USP 1-Aug-2023) Transfer ▲▲(USP 1-Aug-2023) 1 mg of clonidine hydrochloride, from a quantity of finely powdered Tablets, to a separator containing 30 mL of water and 5 mL of 1 N sodium hydroxide. Swirl gently to dissolve the sample specimen, and extract with 20 ml. of chloroform. Allow the layers to separate, and filter the chloroform extract. Evaporate the filtrate to dryness, and dissolve the residue in 0.1 mL of methanol.

2.1 Chromatographic system

(See Chromatography (621), General Procedures, Thin-Layer Chromatography.)

Mode: TLC _{▲(USP 1-Aug-2023)}

Adsorbent: 0.25-mm layer of chromatographic silica gel mixture

Application volume: 2 µL

Developing solvent system: Methanol and ammonium hydroxide (200:3)

2.2 Analysis

Samples: Standard solution and Sample solution

^▲_{▲(USP 1-Aug-2023)} Position the plate in a chromatographic chamber, and develop in Developing solvent system until the solvent front has moved about three-fourths of the length of the plate. Remove the plate from the chamber, mark the solvent front, and allow the solvent to evaporate. Examine the plate under short-wavelength UV light.

Acceptance criteria: The Re value of the principal spot of the Sample solution corresponds to that of the Standard solution.

3 ASSAY

Change to read:

3.1 PROCEDURE

Solution A: 2.2 ^▲ g/L_{▲ (USP 1-Aug-2023)} of octanesulfonic acid sodium salt _{▲(USP 1-Aug-2023)} in water

Mobile phase: Methanol, Solution A, and phosphoric acid (500:500:1). Adjust with 1 N sodium hydroxide to a pH of 3.0.^-▲_{▲(USP 1-Aug-2023)}

Standard stock solution: 100 µg/mL of USP Clonidine Hydrochloride RS in Mobile phase. ^▲ Sonicate to dissolve if necessary. _{▲(USP 1-Aug-2023)}

Standard solution: 1 µg/mL of USP Clonidine Hydrochloride RS (USP 1-Aug-2023) from the Standard stock solution in Mobile phase ^▲_{▲(USP 1-Aug-2023)}

Sample solution: Nominally 1 µg/mL of clonidine hydrochloride in Mobile phase prepared as follows. _{▲(USP 1-Aug-2023)} Weigh and finely powder Tablets (NLT 20). Transfer ^▲a suitable portion _{▲(USP 1-Aug-2023)} equivalent to 0.1 mg of clonidine hydrochloride ^▲_{▲(USP 1-Aug-2023)} to a 100-ml volumetric flask. Add about 60 mL of Mobile phase, shake by mechanical means for 15-30 min, and dilute with Mobile phase to volume ^▲_{▲(USP 1-Aug-2023)} Centrifuge a portion of this solution to obtain a clear solution.

3.2 Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 220 nm

Column: 4.6-mm x 15-cm; packing 17, deactivated for basic compounds

Flow rate: 1.5 mL/min

Injection volume: 50 µL

Run time: NLT 3 times the retention time of clonidine _{▲(USP 1-Aug-2023)}

3.3 System suitability

Sample: Standard solution (USP 1-Aug-2023)

3.4 Suitability requirements

Tailing factor: NMT 1.5

(USP 1-Aug-2023)

Relative standard deviation: NMT 1.0% (USP 1-Aug-2023)

3.5 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of clonidine hydrochloride (C₉H₉Cl₂N₃ · HCl) in the portion of ^▲Tablets _{▲(USP 1-Aug-2023)} taken:

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

r_U = peak response ^▲of clonidine _{▲(USP 1-Aug-2023)} from the Sample solution

r_S = peak response ^▲of clonidine _{▲(USP 1-Aug-2023)} from the Standard solution

C_S = concentration of ^▲USP Clonidine Hydrochloride RS in _{▲(USP 1-Aug-2023)} the Standard solution (µg/mL)

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

Acceptance criteria: 90.0%-110.0%

4 PERFORMANCE TESTS

Change to read:

4.1 DISSOLUTION (711).

Medium: 0.01 N hydrochloric acid: 500 mL

Apparatus 2: 50 rpm

Time: 30 min

Solution A, Mobile phase, Chromatographic system, and System suitability: Proceed as directed in the Assay _{▲(USP 1-Aug-2023)}

Standard solution: Prepare as directed in the Assay, except use Medium instead of Mobile phase.

Sample solution: A portion of the solution under test _{▲(USP 1-Aug-2023)}

4.1.1 Analysis

Samples: Standard solution and Sample solution Calculate the percentage of the labeled amount of clonidine hydrochloride (C₉H₉Cl₂N₃ · HCl) dissolved:

                 Result = (r_U/r_S) x C_S x V x (1/L) x 100

r_U = peak response of clonidine 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 (mg/mL) 

V = volume of Medium, 500 mL

L = label claim (mg/Tablet) _{▲(USP 1-Aug-2023)}

Tolerances: NLT 75% (Q) of the labeled amount of clonidine hydrochloride (C₉H₉Cl₂N₃ · HCl) is dissolved.

UNIFORMITY OF DOSAGE UNITS (905): Meet the requirements

Add the following:

4.2 IMPURITIES

4.2.1 ORGANIC IMPURITIES

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

System suitability solution: 10 µg/mL each of USP Clonidine Hydrochloride RS and USP Clonidine Related Compound C RS in Mobile phase. Sonicate to dissolve if necessary.

Standard solution: 0.2 µg/mL of USP Clonidine Hydrochloride RS in Mobile phase. Sonicate to dissolve if necessary.

Sensitivity solution: 0.04 µg/mL of USP Clonidine Hydrochloride RS from the Standard solution in Mobile phase

Sample solution: Nominally 40 µg/mL of clonidine hydrochloride in Mobile phase prepared as follows. Transfer an appropriate quantity of clonidine hydrochloride from the powdered Tablets (NLT 20) to a suitable volumetric flask. Add Mobile phase to 80% of the total volume and sonicate for 15 min. Dilute with Mobile phase to volume. Centrifuge a portion of this solution and pass the supernatant through a suitable nylon membrane filter of 0.45-µm pore size.

4.2.2 Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 220 nm

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

Flow rate: 1.5 mL/min

Injection volume: 50 µL

Run time: NLT 8 times the retention time of clonidine

4.2.3 System suitability

Samples: System suitability solution, Standard solution, and Sensitivity solution

[NOTE-See Table 1 for the relative retention times.]

4.2.4 Suitability requirements

Resolution: NLT 3.0 between clonidine and clonidine related compound C, System suitability solution

Relative standard deviation: NMT 5.0%, Standard solution

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

4.2.5 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of any specified and unspecified degradation product in the portion of Tablets taken:

                 Result = (r_U/r_S) x (C_S/C_U)× (1/F) × 100

r_U= peak response of any specified or unspecified degradation product from the Sample solution r_{v} = 1

r_S = peak response of clonidine from the Standard solution

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)

F = relative response factor (see Table 1) F = 1

Acceptance criteria: See Table 1. The reporting threshold is 0.1%.

   Table 1

^a Ethane-1,2-diamine 4-methylbenzenesulfonate.

5 ADDITIONAL REQUIREMENTS

Change to read:

• Packaging and Storage: Preserve in well-closed containers. ^▲Store at controlled room temperature._{▲ (USP 1-Aug-2023)}

Change to read:

• USP Reference Standards 〈11〉

USP Clonidine Hydrochloride RS

USP Clonidine Related Compound C RS

Methyl N'-(2,6-dichlorophenyl)carbamimidothioate.

C₈H₈Cl₂N₂S              235.13_{▲ (USP 1-Aug-2023)}