Valsartan

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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C₂₄H₂₉N₅O₃  435.52

l-Valine, N-(1-oxopentyl)-N-[[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-yl]methyl]-;

N-[p-(o-1H-Tetrazol-5-ylphenyl)benzyl]-N-valeryl-l-valine CAS RN®: 137862-53-4; UNII: 80M03YXJ7I.

1 DEFINITION

Valsartan contains NLT 98.0% and NMT 102.0% of valsartan (C₂₄H₂₉N₅O₃), calculated on the anhydrous basis.

2 IDENTIFICATION

Change to read:

A. Spectroscopic Identification Tests 〈197〉, Infrared Spectroscopy: 197M

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

3.1 Procedure

Mobile phase: Acetonitrile, glacial acetic acid, and water (500:1:500)

Standard solution: 0.5 mg/mL of USP Valsartan RS in Mobile phase

Sample solution: 0.5 mg/mL of Valsartan in Mobile phase

Chromatographic system

• (See Chromatography 〈621〉, System Suitability.)
• Mode: LC
• Detector: UV 273 nm
• Column: 3.0-mm × 12.5-cm; 5-µm packing L1
• Flow rate: 0.4 mL/min
• Injection volume: 10 µL

System suitability

• Sample: Standard solution
• Suitability requirements
• Relative standard deviation: NMT 2.0%

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of valsartan (C₂₄H₂₉N₅O₃) in the portion of Valsartan taken:

Result = (rᵤ/rₛ) × (Cₛ/Cᵤ) × 100

rᵤ = peak response of the Sample solution

rₛ = peak response of the Standard solution

Cₛ = concentration of USP Valsartan RS in the Standard solution (mg/mL)

Cᵤ = concentration of Valsartan 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 Procedure 1: Limit of Valsartan Related Compound A

Mobile phase: n-Hexane, 2-propanol, and trifluoroacetic acid (850:150:1)

System suitability solution: 0.04 mg/mL each of USP Valsartan Related Compound A RS and USP Valsartan RS in Mobile phase

Standard solution: 0.01 mg/mL of USP Valsartan Related Compound A RS in Mobile phase

Sample solution: 1 mg/mL of Valsartan in Mobile phase. Sonicate for 5 min.

Chromatographic system

• (See Chromatography 〈621〉, System Suitability.)
• Mode: LC
• Detector: UV 230 nm
• Column: 4.6-mm × 25-cm; 5-µm packing L40
• Flow rate: 0.8 mL/min
• Injection volume: 10 µL

System suitability

• Sample: System suitability solution
• Suitability requirements
• Resolution: NLT 2.0 between valsartan related compound A and valsartan
• Relative standard deviation: NMT 5% for valsartan related compound A peak

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of valsartan related compound A in the portion of Valsartan taken:

Result = (rᵤ/rₛ) × (Cₛ/Cᵤ) × 100

rᵤ = peak response of valsartan related compound A from the Sample solution

rₛ = peak response of valsartan related compound A from the Standard solution

Cₛ = concentration of USP Valsartan Related Compound A RS in the Standard solution (mg/mL)

Cᵤ = concentration of Valsartan in the Sample solution (mg/mL)

Acceptance criteria: NMT 1.0% of valsartan related compound A.

4.3 Procedure 2: Limit of Valsartan Related Compound B, Valsartan Related Compound C, and Other Related Compounds

Mobile phase: Proceed as directed in the Assay.

Standard solution: 1 µg/mL each of USP Valsartan RS, USP Valsartan Related Compound B RS, and USP Valsartan Related Compound C RS in Mobile phase

Sample solution: 0.5 mg/mL of Valsartan in Mobile phase

Chromatographic system: Proceed as directed in the Assay, except for the following.

Detector: UV 225 nm

System suitability

• Sample: Standard solution
• Suitability requirements
• Resolution: NLT 1.8 between valsartan related compound B and valsartan
• Relative standard deviation: NMT 10.0% for valsartan related compound B and NMT 2.0% for valsartan

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of valsartan related compound B and valsartan related compound C in the portion of Valsartan taken:

Result = (rᵤ/rₛ) × (Cₛ/Cᵤ) × 100

rᵤ = peak response of valsartan related compound B or valsartan related compound C from the Sample solution

rₛ = peak response of valsartan related compound B or valsartan related compound C from the Standard solution

Cₛ = concentration of USP Valsartan Related Compound B RS or USP Valsartan Related Compound C RS in the Standard solution (mg/mL)

Cᵤ = concentration of Valsartan in the Sample solution (mg/mL)

Calculate the percentage of any other impurity in the portion of Valsartan taken:

Result = (rᵤ/rₛ) × (Cₛ/Cᵤ) × 100

rᵤ = peak response of any other impurity from the Sample solution

rₛ = peak response of valsartan from the Standard solution

Cₛ = concentration of USP Valsartan RS in the Standard solution (mg/mL)

Cᵤ = concentration of Valsartan in the Sample solution (mg/mL)

Acceptance criteria: See Table 1.

Table 1

ᵃ N-Butyryl-N-{[2′-(1H-tetrazole-5-yl)biphenyl-4-yl]methyl}-l-valine.

ᵇ N-Valeryl-N-{[2′-(1H-tetrazole-5-yl)biphenyl-4-yl]methyl}-l-valine benzyl ester.

ᶜ Excluding valsartan related compound A.

5 SPECIFIC TESTS

Water Determination, Method I 〈921〉: NMT 2.0%

Absorbance

• Analytical wavelength: 420 nm
• Sample solution: A 1-in-20 solution of valsartan in methanol
• Acceptance criteria: The absorbance divided by the path length is NMT 0.02.

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in tight containers, and store at controlled room temperature. Protect from moisture and heat.

USP Reference Standards 〈11〉

USP Valsartan RS

USP Valsartan Related Compound A RS

N-Valeryl-N-{[2′-(1H-tetrazole-5-yl)biphenyl-4-yl]methyl}-D-valine.

C₂₄H₂₉N₅O₃  435.52

USP Valsartan Related Compound B RS

N-Butyryl-N-{[2′-(1H-tetrazole-5-yl)biphenyl-4-yl]methyl}-l-valine.

C₂₃H₂₇N₅O₃  421.49

USP Valsartan Related Compound C RS

N-Valeryl-N-{[2′-(1H-tetrazole-5-yl)biphenyl-4-yl]methyl}-l-valine benzyl ester.

C₃₁H₃₅N₅O₃  525.64