Sildenafil 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 

Sildenafil Injection is a sterile solution of Sildenafil Citrate in Water for Injection. It contains NLT 95.0% and NMT 105.0% of the labeled amount of Sildenafil (C₂₂H₃₀N₆O₄S). It also contains dextrose. 

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. The UV spectrum of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay. 

3 ASSAY 

Procedure 

Solution A: 15.4 g/L of ammonium acetate in water 

Mobile phase: Acetonitrile and Solution A (50:50) 

Standard solution: 0.11 mg/mL of USP Sildenafil Citrate RS in Mobile phase. Sonicate to dissolve if necessary. 

Sample solution: Nominally 0.08 mg/mL of Sildenafil prepared as follows. Transfer 5 mL of Injection to a 50-mL volumetric ask and dilute with Mobile phase to volume. 

Chromatographic system 

(See Chromatography 〈621〉, System Suitability.) 

Mode: LC 

Detector: UV 245 nm. For Identification B, use a diode array detector in the range of 200–400 nm. 

Column: 4.6-mm × 15-cm; 5-µm packing L1 

Flow rate: 1 mL/min 

Injection volume: 20 µL 

Run time: NLT 1.6 times the retention time of Sildenafil 

System suitability 

Sample: Standard solution 

Suitability requirements 

Tailing factor: NMT 2.0 

Relative standard deviation: NMT 1.0% 

Analysis 

Samples: Standard solution and Sample solution 

Calculate the percentage of the labeled amount of Sildenafil (C₂₂H₃₀N₆O₄S) in the portion of Injection taken: 

Result = (r_U/r_S) × (C_S/C_U) × (M_r1/M_r2) × 100 

r_U = peak response of Sildenafil from the Sample solution 

r_S = peak response of Sildenafil from the Standard solution 

C_S = concentration of USP Sildenafil Citrate RS in the Standard solution (mg/mL) 

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

M_r1 = molecular weight of Sildenafil, 474.58  

M_r2 = molecular weight of Sildenafil citrate, 666.70 

Acceptance criteria: 95.0%–105.0% 

4 IMPURITIES 

Organic Impurities 

Dilute phosphoric acid: 10% (v/v) phosphoric acid in water 

Buffer: 3.5 g/L of potassium phosphate, dibasic in water. Adjust with Dilute phosphoric acid to a pH of 7.0. 

Solution A: Acetonitrile and Buffer (14:86) 

Solution B: Acetonitrile and Buffer (74:26) 

Mobile phase: See Table 1. 

Table 1 

Diluent: Methanol and water (50:50) 

Standard stock solution: 0.46 mg/mL of USP Sildenafil Citrate RS in methanol. Sonicate to dissolve if necessary. 

Standard solution: 1.15 µg/mL of USP Sildenafil Citrate RS from the Standard stock solution in Diluent 

Sensitivity solution: 0.575 µg/mL of USP Sildenafil Citrate RS from the Standard solution in Diluent 

Sample solution: Nominally 0.4 mg/mL of Sildenafil prepared as follows. Transfer 5 mL of Injection to a 10-mL volumetric ask and dilute with methanol to volume. 

Chromatographic system 

(See Chromatography 〈621〉, System Suitability.) 

Mode: LC 

Detector: UV 240 nm 

Column: 4.6-mm × 15-cm; 5-µm packing L1 

Column temperature: 30° 

Flow rate: 1 mL/min 

Injection volume: 20 µL 

System suitability 

Samples: Standard solution and Sensitivity solution 

Suitability requirements 

Tailing factor: NMT 2.0, Standard solution 

Relative standard deviation: NMT 5.0%, Standard solution 

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

Analysis 

Samples: Standard solution and Sample solution 

Calculate the percentage of Sildenafil N-oxide and any unspecified degradation product in the portion of Injection taken: 

Result = (r_U/r_S) × (C_S/C_U) × (M_r1/M_r2) x (1/F) × 100 

r_U = peak response of each degradation product from the Sample solution

r_S = peak response of Sildenafil from the Standard solution 

C_S = concentration of USP Sildenafil Citrate RS in the Standard solution (mg/mL) 

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

M_r1 = molecular weight of Sildenafil, 474.58  

M_r2 = molecular weight of Sildenafil citrate, 666.70 

F = relative response factor (see Table 2) 

Acceptance criteria: See Table 2. The reporting threshold is 0.1%. 

Table 2 

a 4-[(4-Ethoxy-3-(1-methyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-5-yl)phenyl)sulfonyl]-1-methylpiperazine 1-oxide. 

5 SPECIFIC TESTS 

pH 〈791〉: 3.5–4.5 

Particulate Matter in Injections 〈788〉: Meets the requirements 

Sterility Tests 〈71〉: Meets the requirements 

Bacterial Endotoxins Test 〈85〉: Meets the requirements 

6 ADDITIONAL REQUIREMENTS 

Packaging and Storage: Preserve in single-dose glass containers. Store at controlled room temperature. 

USP Reference Standards 〈11〉 

USP 5-Hydroxymethylfurfural RS 

5-(Hydroxymethyl)furan-2-carbaldehyde. 

C₆H₆O₃ 126.11 

USP Sildenafil Citrate RS