Vardenafil Hydrochloride

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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C₂₃H₃₂N₆O₄S · HCI · 3H₂O            579.11

Piperazine, 1-[[3-(1,4-dihydro-5-methyl-4-oxo-7-propylimidazo[5,1-f][1,2,4]triazin-2-yl)-4-ethoxyphenyl]sulfonyl]-4-ethyl-, monohydrochloride, trihydrate-;

2-[2-Ethoxy-5-(4-ethyl-piperazine-1-sulfonyl)-phenyl]-5-methyl-7-propyl-3H-imidazo[5,1-f][1,2,4]triazin-4-one, hydrochloride, trihydrate CAS RN 330808-88-3; UNII: 5M8S2CUOTS.

Anhydrous          525.06 CAS RN: 224785-91-5; UNII: IF61NL91H3.

1 DEFINITION

Vardenafil Hydrochloride contains NLT 98.0% and NMT 102.0% of vardenafil hydrochloride (C₂₃H₃₂N₆O₄S · HCI), calculated on the anhydrous basis.

2 IDENTIFICATION

Change to read:

A. ^▲SPECTROSCOPIC IDENTIFICATION TESTS (197), Infrared Spectroscopy: 197K_{▲(CN 1-MAY-2020)}

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

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

3 ASSAY

PROCEDURE

Protect all solutions containing vardenafil from light.

Buffer: Dissolve 1.3 g of monobasic potassium phosphate and 0.7 g of dibasic sodium phosphate dihydrate in 1 L of water.

Mobile phase: See Table 1. Return to original conditions, and re-equilibrate the system.

Table 1

System suitability solution: 0.5 mg/mL of USP Vardenafil System Suitability RS prepared as follows. Transfer an appropriate quantity of the Reference Standard to a volumetric flask. Add 20% of the flask volume of acetonitrile and dilute with Buffer to volume.

Standard solution: 0.15 mg/mL of USP Vardenafil Hydrochloride RS prepared as follows. Transfer an appropriate quantity of USP Vardenafil Hydrochloride RS to a volumetric flask. Add 20% of the flask volume of acetonitrile and dilute with Buffer to volume.

Sample solution: 0.15 mg/mL of Vardenafil Hydrochloride prepared as follows. Transfer an appropriate quantity of Vardenafil Hydrochloride to a volumetric flask. Add 20% of the flask volume of acetonitrile and dilute with Buffer to volume.

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 242 nm

Column: 3-mm x 25-cm; 5-µm packing L1

Column temperature: 45°

Flow rate: 0.5 mL/min

Injection volume: 10 μL

System suitability

Samples: System suitability solution and Standard solution

Suitability requirements

Resolution: NLT 5.0 between vardenafil and 7-methyl vardenafil, System suitability solution

Relative standard deviation: NMT 0.85%, Standard solution

Tailing factor: 0.8-1.5, Standard solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of vardenafil hydrochloride (C₂₃H₃₂N₆O₄S · HCI) in the portion of Vardenafil Hydrochloride taken:

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

r_U = peak response of vardenafil from the Sample solution

r_S = peak response of vardenafil from the Standard solution 

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

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

Acceptance criteria: 98.0%-102.0% on the anhydrous basis

4 IMPURITIES

4.1 RESIDUE ON IGNITION (281)

NMT 0.1%

4.2 ORGANIC IMPURITIES

Protect all solutions containing vardenafil from light.

Buffer, Mobile phase, System suitability solution, and Chromatographic system: Proceed as directed in the Assay.

Diluent: Acetonitrile and Buffer (20:80)

Standard stock solution: 0.5 mg/ml. of USP Vardenafil Hydrochloride RS prepared as follows. Transfer an appropriate quantity of the Reference Standard to a volumetric flask. Add 20% of the flask volume of acetonitrile and dilute with Buffer to volume.

Standard solution: 0.5 µg/mL of USP Vardenafil Hydrochloride RS in Diluent from the Standard stock solution

Sample solution: 0.5 mg/ml. of Vardenafil Hydrochloride prepared as follows. Transfer an appropriate quantity of Vardenafil Hydrochloride to a volumetric flask. Add 20% of the flask volume of acetonitrile and dilute with Buffer to volume.

System suitability

[NOTE-See Table 2 for the relative retention times.]

Samples: System suitability solution and Standard solution

Suitability requirements

Resolution: NLT 5.0 between vardenafil and 7-methyl vardenafil, System suitability solution

Relative standard deviation: NMT 5.0%, Standard solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of each impurity in the portion of Vardenafil Hydrochloride taken:

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

r_U = peak response of each impurity from the Sample solution

r_S = peak response of vardenafil from the Standard solution

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

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

Acceptance criteria: See Table 2. Disregard any impurity peak less than 0.05%.

Table 2

^a 2-(2-Ethoxy-5-[(4-ethylpiperazin-1-yl) sulfonyl)phenyl)-5,7-dimethylimidazo [5,1-f][1,2,4]triazin-4(3H)-one.

^b 4-Ethoxy-3-(5-methyl-4-oxo-7-propyl-3,4-dihydroimidazo [5,1-f[1,2,4]triazin-2-yl)benzenesulfonic acid.

^c 2,2'-[(Piperazine-1,4-disulfonyl)bis(6-ethoxy-3,1-phenylene)]bis[5-methyl-7-propylimidazo[5,1-f][1,2,4]-triazin-4(3H)-one.

5 SPECIFIC TESTS

WATER DETERMINATION, Method (921): 8.8%-10.5%

6 ADDITIONAL REQUIREMENTS

PACKAGING AND STORAGE: Store in well-closed containers at room temperature.

USP REFERENCE STANDARDS (11)

USP Vardenafil Hydrochloride RS

USP Vardenafil Svatem Suitability RS

This mixture contains Vardenafil Hydrochloride and approximately 1% of 7-methyl vardenafil (2-(2-ethoxy-5-[(4-ethylpiperazin-1-yl) sulfonyl)phenyl)-5,7-dimethylimidazo[5,1-f][1,2,4]triazin-4(3H)-one).

C₂₁H₂₈N₆O₄S                460.55