Hydralazine 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

Hydralazine Hydrochloride Tablets contain NLT 90.0% and NMT 110.0% of the labeled amount of hydralazine hydrochloride (C₈H₈N₄ · HCl).

2 IDENTIFICATION

Change to read:

A. Spectroscopic Identification Tests 〈197〉, Infrared Spectroscopy: 197K (CN 1-May-2020)

Sample: Transfer an amount equivalent to about 100 mg of hydralazine hydrochloride from finely powdered Tablets to a glass-stoppered ask. Add 40 mL of 1 N hydrochloric acid, shake by mechanical means for 5 min, and filter. Discard the first few milliliters of the filtrate. Place 20 mL of the filtrate in a separator, wash with 10 mL of methylene chloride, and discard the washing. Mix the aqueous solution in the separator with 2 mL of 14 mg/mL sodium nitrite solution, add 10 mL of methylene chloride, shake by mechanical means for 5 min, and allow the layers to separate. Pass the methylene chloride layer through a filter of anhydrous sodium sulfate previously washed with methylene chloride and collect the solution in a 50-mL beaker. Evaporate to dryness with the aid of gentle heat and a stream of dry nitrogen. Acceptance criteria: Meet the requirements

B. The retention time of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay.

3 ASSAY

Procedure

Mobile phase: Dissolve 1.44 g of sodium dodecyl sulfate and 0.75 g of tetrabutylammonium bromide in 770 mL of water and add 230 mL of acetonitrile. Adjust with 0.1 N sulfuric acid to a pH of 3.0.

Diluent: 0.1 N acetic acid

System suitability solution: 25 µg/mL of USP Hydralazine Hydrochloride RS and 5 µg/mL of USP Phthalazine RS in Diluent Standard solution: 40 µg/mL of USP Hydralazine Hydrochloride RS in Diluent

Sample stock solution: Nominally 0.4 mg/mL of hydralazine hydrochloride from NLT 20 finely powdered Tablets in Diluent. Centrifuge the solution and use the clear supernatant.

Sample solution: Nominally 40 µg/mL of hydralazine hydrochloride in Diluent from the Sample stock solution

3.1 Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 230 nm

Column: 4.0-mm × 25-cm; 10-µm packing L10

Flow rate: 1 mL/min

Injection volume: 25 µL

3.2 System suitability

Samples: System suitability solution and Standard solution

[Note—The relative retention times for phthalazine and hydralazine are about 0.65 and 1.0, respectively.]

Suitability requirements

Resolution: NLT 4.0 between the phthalazine and hydralazine peaks, System suitability solution

Relative standard deviation: NMT 2.0%, Standard solution

3.3 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of hydralazine hydrochloride (C₈H₈N₄ · HCl) in the portion of Tablets taken:

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

r_U = peak response of hydralazine from the Sample solution

r_S = peak response of hydralazine from the Standard solution

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

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

Acceptance criteria: 90.0%–110.0%

4 PERFORMANCE TESTS

Dissolution 〈711〉

Medium: 0.01 N hydrochloric acid; 900 mL

Apparatus 1: 100 rpm

Time: 45 min

Standard solution: A known concentration of USP Hydralazine Hydrochloride RS in Medium

Sample solution: Pass a portion of the solution under test through a suitable filter and dilute with Medium, if necessary, to a concentration similar to that of the Standard solution.

4.1 Instrumental conditions

Mode: UV

Analytical wavelength: Maximum absorbance at about 260 nm

Analysis

Samples: Standard solution and Sample solution

Determine the percentage of the labeled amount of hydralazine hydrochloride (C₈H₈N₄ · HCl) dissolved.

Tolerances: NLT 75% (Q) of the labeled amount of hydralazine hydrochloride (C₈H₈N₄· HCl) is dissolved.

Uniformity of Dosage Units 〈905〉: Meet the requirements 

5 IMPURITIES 

Organic Impurities 

Diluent and System suitability solution: Prepare as directed in the Assay. 

Mobile phase: Dissolve 1.44 g of sodium dodecyl sulfate and 0.75 g of tetrabutylammonium bromide in 770 mL of water, adjust with 0.1 N sulfuric acid to a pH of 3.0, and add 230 mL of acetonitrile. 

Standard stock solution: 0.1 mg/mL of USP Hydralazine Hydrochloride RS in Diluent, prepared as follows. To a suitable amount of USP Hydralazine Hydrochloride RS, add 60% of the total volume of Diluent, sonicate to dissolve, cool to room temperature, and then dilute with Diluent to volume. 

Standard solution: 0.001 mg/mL of USP Hydralazine Hydrochloride RS in Diluent from the Standard stock solution 

Sample solution: Nominally 0.5 mg/mL of hydralazine hydrochloride from NLT 20 powdered Tablets in Diluent, prepared as follows. To a suitable amount of powdered Tablets, add 60% of the total volume of Diluent and sonicate for 15 min with occasional swirling. Cool to room temperature, dilute with Diluent to volume, and pass through a suitable filter of 0.45-µm pore size. 

5.1 Chromatographic system

Proceed as directed in the Assay except for the following. 

Injection volume: 20 µL 

Run time: NLT 5.8 times the retention time of hydralazine 

5.2 System suitability 

Samples: System suitability solution and Standard solution 

Suitability requirements 

Resolution: NLT 4.0 between the phthalazine and hydralazine peaks, System suitability solution 

Relative standard deviation: NMT 5.0%, Standard solution 

5.3 Analysis 

Samples: Standard solution and Sample solution 

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

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

r_U = peak response of any unspecified degradation product from the Sample solution 

r_S = peak response of hydralazine from the Standard solution 

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

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

F = relative response factor (see Table 1)

Acceptance criteria: See Table 1.

Table 1

^a Process-related impurity.

^b Total impurities include process-related impurities and degradation products.

6 ADDITIONAL REQUIREMENTS

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

USP Reference Standards 〈11〉

USP Hydralazine Hydrochloride RS

USP Phthalazine RS               C₈H₆N₂              130.15