Guanfacine 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

Guanfacine Tablets contain an amount of Guanfacine Hydrochloride (C₉H₉Cl₂N₃O · HCl) equivalent to NLT 90.0% and NMT 110.0% of the labeled amount of guanfacine (C₉H₉Cl₂N₃O).

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. Thin-Layer Chromatographic Identification Test 〈201〉

Standard solution: 2 mg/mL of USP Guanfacine Hydrochloride RS in methanol

Sample solution: 2 mg/mL in methanol

Developing solvent system: Ethyl acetate, glacial acetic acid, and water (5:2:2)

Acceptance criteria: Meet the requirements

3 ASSAY

3.1 Procedure

Solution A: pH 2.5 diethylamine phosphate prepared as follows. Add 10.3 mL of diethylamine to 70 mL of water. Adjust with phosphoric acid to a pH of 2.5 and dilute with water to 100 mL.

Mobile phase: Dissolve 600 mg of monobasic potassium phosphate and 3 mL of Solution A in 480 mL of water, and mix. Adjust with 0.2 N sodium hydroxide to a pH of 4.0. While swirling, add 520 mL of acetonitrile.

Standard stock solution A: 0.018 mg/mL of 2,6-dichlorophenylacetic acid in Mobile phase

Standard stock solution B: 0.23 mg/mL of USP Guanfacine Hydrochloride RS in Mobile phase

Internal standard solution: 0.5 mg/mL of butylparaben in Mobile phase

Standard solution: 0.046 mg/mL of USP Guanfacine Hydrochloride RS, 3.6 μg/mL of 2,6-dichlorophenylacetic acid and 0.1 mg/mL of butylparaben in Mobile phase prepared as follows. Transfer 5.0 mL each of Standard stock solution A, Standard stock solution B and Internal standard solution to a 25-mL volumetric flask and dilute with Mobile phase to volume.

Sample stock solution: Nominally 0.1 mg/mL of guanfacine in Mobile phase prepared as follows. Finely powder NLT 20 Tablets. Transfer an accurately weighed portion of the powder, equivalent to 10 mg of guanfacine, to a 100-mL volumetric flask. Add 50 mL of Mobile phase and heat on a steam bath for 5 min. Cool to room temperature and dilute with Mobile phase to volume.

Sample solution: Nominally 0.04 mg/mL of guanfacine and 0.1 mg/mL of butylparaben in Mobile phase prepared as follows. Transfer 10.0mL of Sample stock solution to a 25-mL volumetric flask, add 5.0 mL of Internal standard solution and dilute with Mobile phase to volume.

3.2 Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 220 nm

Column: 3.9-mm × 30-cm; packing L1

Flow rate: 1 mL/min

Injection volume: 20 μL

3.3 System suitability

Sample: Standard solution

[Note - The relative retention times for guanfacine, 2,6-dichlorophenylacetic acid, and butylparaben are 0.4, 0.6, and 1.0, respectively.]

3.4 Suitability requirements

Resolution: NLT 1.5 between guanfacine and 2,6-dichlorophenylacetic acid and NLT 1.5 between 2,6-dichlorophenylacetic acid and butylparaben

Relative standard deviation: NMT 2.0%

3.5 Analysis

Samples: Sample solution and Standard solution

Calculate the percentage of guanfacine (C₉H₉Cl₂N₃O) in the portion of Tablets taken:

Result = (R_U/R_S) × (C_S/C_U) × (M_r1/M_r2) × 100

R_U = peak response ratio of guanfacine to butylparaben from the Sample solution

R_S = peak response ratio of guanfacine to butylparaben from the Standard solution

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

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

M_r1 = molecular weight of guanfacine, 246.09

M_r2 = molecular weight of guanfacine hydrochloride, 282.55

Acceptance criteria: 90.0% - 110.0%

4 PERFORMANCE TESTS

Change to read:

Dissolution 〈711〉

4.1 Test 1

Medium: water; 500 mL

Apparatus 2: 50 rpm

Time: 45 min

Analysis: Determine the amount of guanfacine (C₉H₉Cl₂N₃O) dissolved using the procedure in the Assay, and making any necessary modifications.

Tolerances: NLT 75% (Q) of the labeled amount of guanfacine (C₉H₉Cl₂N₃O) is dissolved.

4.2 Test 2

If the product complies with this test, the labeling indicates that it meets USP Dissolution Test 2.

Medium: 0.1 N hydrochloric acid; 500 mL, deaerated, if necessary (RB 1-Feb-2024)

Apparatus 2: 50 rpm

Time: 30 min

Solution A: Add 10.3 mL of diethylamine to 70 mL of water. Adjust with phosphoric acid to a pH of 2.5. Dilute to 100 mL with water.

Mobile phase: Dissolve 662.5 mg of potassium phosphate, monobasic and 3 mL of Solution A in 530 mL of water. Adjust with 0.2 N sodium hydroxide solution to a pH of 4.0. Add 470 mL of acetonitrile and mix.

Standard solution: (L/500) mg/mL of guanfacine from USP Guanfacine Hydrochloride RS in Medium, where L is the label claim in mg/Tablet. Sonicate to dissolve.

Sample solution: Pass a portion of the solution under test through a suitable filter of 0.45-μm pore size, discarding the first 3 mL of the filtrate.

4.2.1 Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 220 nm

Column: 3.9-mm × 30-cm; 10-μm packing L1

Flow rate: 1 mL/min

Injection volume: 20 μL

Run time: NLT 3 times the retention time of guanfacine

4.2.2 System suitability

Sample: Standard solution

4.2.3 Suitability requirements

Tailing factor: NMT 2.0

Relative standard deviation: NMT 2.0%

4.2.4 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of guanfacine (C₉H₉Cl₂N₃O) dissolved:

Result = (r_U/r_S) × C_S × V × (M_r1/M_r2) × (1/L) × 100

r_U = peak response of guanfacine from the Sample solution

r_S = peak response of guanfacine from the Standard solution

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

V = volume of Medium, 500 mL

M_r1 = molecular weight of guanfacine, 246.09

M_r2 = molecular weight of guanfacine hydrochloride, 282.55

L = label claim (mg/Tablet)

Tolerances: NLT 80% (Q) of the labeled amount of guanfacine (C₉H₉Cl₂N₃O) is dissolved.

Uniformity of Dosage Units 〈905〉: Meet the requirements

5 ADDITIONAL REQUIREMENTS

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

Labeling: When more than one Dissolution test is given, the labeling states the Dissolution test used only if Test 1 is not used.

USP Reference Standards 〈11〉

USP Guanfacine Hydrochloride RS