Losartan Potassium 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

Losartan Potassium Tablets contain NLT 95.0% and NMT 105.0% of the labeled amount of losartan potassium (C₂₂H₂₂ClKN₆O).

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.

3 ASSAY

Procedure

Buffer: 1.25 mg/mL of monobasic potassium phosphate and 1.5 mg/mL of dibasic sodium phosphate in water. The resulting pH is approximately 7.0. Pass the solution through a PTFE or equivalent filter of 0.45-μm pore size, and degas before use.

Solution A: Acetonitrile and Buffer (15:85)

Solution B: Use acetonitrile.

Mobile phase: See Table 1.

Table 1

System suitability stock solution: Dissolve 12 mg of USP Losartan Potassium RS in a 50-mL volumetric flask, first using 5 mL of water, followed by 5 mL of 0.1 N hydrochloric acid. Place the flask in a 105° oven for 1–2 h, and allow to cool to room temperature. Pipet 5 mL of 0.1 N sodium hydroxide into the flask, and dilute with water to volume. Adjust with either 0.1 N hydrochloric acid or 0.1 N sodium hydroxide to a pH of 6.0. [Note—The resulting solution contains the 1H-dimer and 2H-dimer, and the resulting solution may be cloudy.]

System suitability solution: Add 3 mL of acetonitrile to 7 mL of System suitability stock solution to clear the cloudy solution, and mix well.

Standard solution: 0.25 mg/mL of USP Losartan Potassium RS in Solution A. Pass through a PTFE or equivalent filter of 0.45-μm pore size.

Sample stock solution: Transfer 10 Tablets to a 500-mL volumetric flask, add Solution A to fill the flask to about 50% of the final volume, and sonicate with intermittent shaking for 15 min. Sonicate for an additional 10 min. Dilute with Solution A to volume, and mix well.

Sample solution: 0.25 mg/mL of losartan potassium in Solution A from the Sample stock solution. Mix well. Pass an aliquot of the solution through a PTFE filter of 0.45-μm pore size, and use the filtrate.

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 250 nm

Column: 3.9-mm × 15-cm; 5-μm packing L7

Flow rate: 1.0 mL/min

Injection volume: 10 μL

System suitability

Samples: System suitability solution and Standard solution

Suitability requirements

Tailing factor: NMT 2.0 for the losartan, 1H-dimer, and 2H-dimer peaks; System suitability solution

Resolution: NLT 2.0 between the 1H-dimer and 2H-dimer, System suitability solution

Column efficiency: NLT 3000 theoretical plates, Standard solution

Tailing factor: NMT 2.0, Standard solution

Relative standard deviation: NMT 2.0%, Standard solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of losartan potassium (C₂₂H₂₂ClKN₆O) in the portion of Tablets taken:

Result = (r_U/r_S) × (C_S/C_U) × 100

r_U = peak response of losartan from the Sample solution

r_S = peak response of losartan from the Standard solution

C_S = concentration of USP Losartan Potassium RS in the Standard solution (mg/mL)

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

Acceptance criteria: 95.0%–105.0%

4 PERFORMANCE TESTS

Dissolution 〈711〉

Test 1

Medium: Water; 900 mL, deaerated

Apparatus 2: 50 rpm

Time: 30 min

Standard solution: (L/1000) mg/mL of USP Losartan Potassium RS in Medium, where L is the Tablet label claim, in mg

Sample solution: Pass a portion of the solution under test through a suitable filter of 0.45-μm pore size.

Analysis: Determine the amount of losartan potassium (C H ClKN O) dissolved by using one of the following procedures:

Instrumental conditions

Analytical wavelength: Maximum absorbance at about 256 nm

Path length: See Table 2 or make the appropriate dilution of the solutions with Medium to be within the linearity range of the spectrophotometer.

Table 2

Blank: Medium

Calculate the percentage of the labeled amount of losartan potassium (C₂₂H₂₂ClKN₆O) dissolved:

Result = (A_U/A_S) × (C_S/L) × V × 100

A_U = absorbance of the Sample solution

A_S = absorbance of the Standard solution

C_S = concentration of USP Losartan Potassium RS in the Standard solution (mg/mL)

L = label claim (mg/Tablet)

V = volume of Medium, 900 mL

Chromatographic procedure

Solution A: 0.1% v/v phosphoric acid in water

Mobile phase: Acetonitrile and Solution A (40:60)

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 254 nm

Column: 4.0-mm × 25-cm; 5-μm packing L1

Column temperature: 35°

Flow rate: 1 mL/min

Injection volume: 20 μL

Run time: NLT 1.5 times the retention time of losartan

System suitability

Sample: Standard solution

Suitability requirements

Tailing factor: NMT 2.0

Relative standard deviation: NMT 2.0%

Calculate the percentage of the labeled amount of losartan potassium (C₂₂H₂₂ClKN₆O) dissolved:

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

r_U = peak response from the Sample solution

r_S = peak response from the Standard solution

C_S = concentration of USP Losartan Potassium RS in the Standard solution (mg/mL)

V = volume of Medium, 900 mL

L = label claim (mg/Tablet)

Tolerances: NLT 75% (Q) of the labeled amount of losartan potassium (C₂₂H₂₂ClKN₆O) is dissolved.

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

Medium: Water; 900 mL

Apparatus 2: 75 rpm

Time: 30 min

Buffer: 1.4 g/L of anhydrous monobasic potassium phosphate in water. Adjust with phosphoric acid to a pH of 3.3 ± 0.1.

Mobile phase: Methanol, acetonitrile, and Buffer (20:20:60)

Standard solution: 0.028 mg/mL of USP Losartan Potassium RS in Medium

Sample solution

For Tablets labeled to contain 25 mg: Pass a portion of the solution under test through a suitable filter of 0.45-μm pore size.

For Tablets labeled to contain 50 and 100 mg: Pass a portion of the solution under test through a suitable filter of 0.45-μm pore size.

Further dilute the filtrate with Medium to prepare a 0.028-mg/mL solution.

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 265 nm

Column: 4.6-mm × 15-cm; 5-μm packing L10

Column temperature: 45°

Flow rate: 1.5 mL/min

Injection volume: 10 μL

System suitability

Sample: Standard solution

Suitability requirements

Tailing factor: NMT 2.0

Relative standard deviation: NMT 2.0%

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of losartan potassium (C₂₂H₂₂ClKN₆O) dissolved:

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

r_U = peak response from the Sample solution

r_S = peak response from the Standard solution

C_S = concentration of USP Losartan Potassium RS in the Standard solution (mg/mL)

L = label claim (mg/Tablet)

V = volume of Medium, 900 mL

Tolerances: NLT 85% (Q) of the labeled amount of losartan potassium (C H ClKN O) is dissolved.

Test 3: If the product complies with this test, the labeling indicates that the product meets USP Dissolution Test 3.

Medium: Water; 900 mL, deaerated

Apparatus 2: 50 rpm

Time: 30 min for 25-mg and 50-mg Tablet strengths, and 45 min for 100-mg Tablet strength

Buffer: 0.025 M phosphoric acid. Adjust with 1 N sodium hydroxide to a pH of 2.15.

Mobile phase: Acetonitrile and Buffer (400:600)

Standard stock solution: 0.27 mg/mL of USP Losartan Potassium RS prepared as follows. Add methanol to USP Losartan Potassium RS to fill about 10% of the volume of the flask, and add Medium to fill about 50% of the volume of the flask. Sonicate for NLT 15 min. Cool to room temperature, and dilute with Medium to volume.

Standard solution: Prepare as directed in Table 3 from the Standard stock solution.

Table 3

Sample solution: Pass a portion of the solution under test through a suitable polyethylene filter of 10-μm pore size.

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 220 nm

Column: 4.6-mm × 10-cm; 3.5-μm packing L7

Column temperature: 40°

Flow rate: 1.5 mL/min

Injection volume: 10 μL

System suitability

Sample: Standard solution

Suitability requirements

Tailing factor: NMT 2.0

Relative standard deviation: NMT 2.0%

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of losartan potassium (C₂₂H₂₂ClKN₆O) dissolved:

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

r_U = peak response of losartan from the Sample solution

r_S = peak response of losartan from the Standard solution

C_S = concentration of USP Losartan Potassium RS in the Standard solution (mg/mL)

L = label claim (mg/Tablet)

V = volume of Medium, 900 mL

Tolerances: NLT 75% (Q) of the labeled amount of losartan potassium (C₂₂H₂₂ClKN₆O) is dissolved for 25-mg and 50-mg Tablet strengths.

NLT 80% (Q) of the labeled amount of losartan potassium (C₂₂H₂₂ClKN₆O) is dissolved for 100-mg Tablet strength.

Change to read:

Uniformity of Dosage Units 〈905〉: Meet the requirements (CN 1-Aug-2023)

Procedure for content uniformity

Buffer: Dissolve 1.36 mg/mL of monobasic potassium phosphate in water. Adjust with phosphoric acid to a pH of 2.5.

Diluent: Dissolve 17.42 g of dibasic potassium phosphate in 900 mL of water. Adjust with phosphoric acid to a pH of 8.0. Dilute with water to a volume of 1000 mL, and mix well. Further dilute with water (1 in 10), and mix well.

Mobile phase: Acetonitrile and Buffer (60:40)

Standard solution: 0.05 mg/mL of USP Losartan Potassium RS in Diluent

Sample stock solution: Transfer 1 Tablet to a 100-mL volumetric flask, add about 65 mL of Diluent, and shake mechanically for 30 min.

Dilute with Diluent to volume, and mix well.

Sample solution: 0.05 mg/mL of losartan potassium in Diluent from the Sample stock solution. Filter an aliquot of the solution, and use the filtrate.

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 230 nm

Column: 4.6-mm × 25-cm; 10-μm packing L7

Flow rate: 1.4 mL/min

Injection volume: 20 μL

System suitability

Sample: Standard solution

Suitability requirements

Column e

ciency: NLT 3000 theoretical plates

Relative standard deviation: NMT 2.0%

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of losartan potassium (C₂₂H₂₂ClKN₆O) in the portion of the Tablet taken:

Result = (r_U/r_S) × (C_S/C_U) × 100

r_U = peak response of losartan from the Sample solution

r_S = peak response of losartan from the Standard solution

C_S = concentration of USP Losartan Potassium RS in the Standard solution (mg/mL)

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

(CN 1-Aug-2023)

5 IMPURITIES

Organic Impurities

Solution A, Solution B, Mobile phase, System suitability solution, Sample solution, and Chromatographic system: Prepare as directed in the Assay.

Standard stock solution: Use the Standard solution, prepared as directed in the Assay.

Standard solution: 2.5 μg/mL of USP Losartan Potassium RS in Solution A from the Standard stock solution

Sensitivity solution: Dilute 1 mL of the Standard solution to 10 mL in Solution A.

System suitability

Samples: System suitability solution, Standard solution, and Sensitivity solution

Suitability requirements

Tailing factor: NMT 2.0 for the losartan, 1H-dimer, and 2H-dimer peaks; System suitability solution

Resolution: NLT 2.0 between the 1H-dimer and 2H-dimer, System suitability solution

Column efficiency: NLT 3000 theoretical plates, Standard solution

Tailing factor: NMT 2.0, Standard solution

Relative standard deviation: NMT 5.0%, Standard solution

Signal-to-noise ratio: NLT 10 for the losartan peak from the first injection. If this is not met, then the Signal-to-noise ratio must be greater than 3 with a relative standard deviation of area counts less than 25% for three replicate injections, Sensitivity solution.

Analysis

Samples: Standard solution and Sample solution

[Note—Identify the peaks using the relative retention times provided in Table 4.]

Calculate the percentage of each impurity in the portion of Tablets taken:

Result = (r_U/r_S) × (C_S/C_U) × 100

r_U = peak response of each individual impurity from the Sample solution

r_S = peak response of losartan from the Standard solution

C_S = concentration of USP Losartan Potassium RS in the Standard solution (mg/mL)

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

Acceptance criteria: See Table 4.

Table 4

a 5-[4′-({2-Butyl-5-[(5-{4′-[(2-butyl-4-chloro-5-hydroxymethyl-1H-imidazol-1-yl)methyl]biphenyl-2-yl}-1H-tetrazol-1-yl)methyl]-4-chloro-1H-imidazol-1-yl}methyl)biphenyl-2-yl]tetrazol, potassium salt.

b 5-[4′-({2-Butyl-5-[(5-{4′-[(2-butyl-4-chloro-5-hydroxymethyl-1H-imidazol-1-yl)methyl]biphenyl-2-yl}-2H-tetrazol-2-yl)methyl]-4-chloro-1H-imidazol-1-yl}methyl)biphenyl-2-yl]tetrazol, potassium salt.

c The total impurities include the sum of all the specified impurities and the sum of all the unspecified impurities. Disregard peaks less than 0.1%.

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Store in tightly closed containers, protected from light, at controlled room temperature.

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

USP Reference Standards 〈11〉

USP Losartan Potassium RS