Losartan Potassium Tablets
711
Test 1(RB 1-Jul-2011)
Test 2:
If the product complies with this test, the labeling indicates that the product meets USP Dissolution Test 2.
• Labeling:
When more than one Dissolution test is given, the labeling states the test used only if Test 1 is not used.(RB 1-Jul-2011)
DEFINITION
Losartan Potassium Tablets contain NLT 95.0% and NMT 105.0% of the labeled amount of losartan potassium (C22H22ClKN6O).
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.
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 (3:17)
Solution B:
Use acetonitrile.
Mobile phase:
See Table 1.
Table 1
| Time (min) |
Solution A (%) |
Solution B (%) |
|---|---|---|
| 0 | 80 | 20 |
| 10 | 40 | 60 |
| 11 | 80 | 20 |
| 15 | 80 | 20 |
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. ]
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
Mode:
LC
Detector:
UV 250 nm
Column:
3.9-mm × 15-cm; 5-µm packing L7
Flow rate:
1.0 mL/min
Injection size:
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 = (rU/rS) × (CS/CU) × 100
| rU | = | = peak response of losartan from the Sample solution |
| rS | = | = peak response of losartan from the Standard solution |
| CS | = | = concentration of USP Losartan Potassium RS in the Standard solution (mg/mL) |
| CU | = | = nominal concentration of losartan potassium in the Sample solution (mg/mL) |
Acceptance criteria:
95.0%–105.0%
PERFORMANCE TESTS
Change to read:
• Dissolution 711
Test 1(RB 1-Jul-2011)
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 (C22H22ClKN6O) dissolved by using UV absorption at the wavelength of maximum absorbance at about 256 nm on portions of the Sample solution in comparison with the Standard solution, using Medium as blank. Use the appropriate cell size as listed in Table 2, or make the appropriate dilution of the solutions with Medium to be within the linearity range of the spectrophotometer.
Table 2
| Tablet Strength (mg/Tablet) |
Cell Size (cm) |
|---|---|
| 25 | 1.0 |
| 50 | 0.5 |
| 100 | 0.2 |
Calculate the percentage of losartan potassium (C22H22ClKN6O) dissolved:
Result = (AU/AS) × (CS/L) × V × 100
| AU | = | = absorbance of the Sample solution |
| AS | = | = absorbance of the Standard solution |
| CS | = | = 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.
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
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 size:
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 = (rU/rS) × (CS/L) × V × 100
| rU | = | = peak response from the Sample solution |
| rS | = | = peak response from the Standard solution |
| CS | = | = 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 (C22H22ClKN6O) is dissolved.(RB 1-Jul-2011)
(RB 1-Jul-2011)
• Uniformity of Dosage Units 905
905
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. Prepare a dilution in water (1 in 10), and mix well.
Mobile phase:
Acetonitrile and Buffer (3:2)
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
Mode:
LC
Detector:
UV 230 nm
Column:
4.6-mm × 25-cm; 10-µm packing L7
Flow rate:
1.4 mL/min
Injection size:
20 µL
System suitability
Sample:
Standard solution
Suitability requirements
Column efficiency:
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 = (rU/rS) × (CS/CU) × 100
| rU | = | = peak response of losartan from the Sample solution |
| rS | = | = peak response of losartan from the Standard solution |
| CS | = | = concentration of USP Losartan Potassium RS in the Standard solution (mg/mL) |
| CU | = | = concentration of losartan in the Sample solution (mg/mL) |
Acceptance criteria:
Meet the requirements
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
Limit of quantitation solution:
Dilute Standard solution in Solution A (1 in 10).
System suitability
Samples:
System suitability solution, Standard solution, and Limit of quantitation solution
Suitability requirements
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, Limit of quantitation solution.
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
Analysis
Samples:
Standard solution and Sample solution
[Note—Identify the peaks using the relative retention times provided in Table 3. ]
Calculate the percentage of each impurity in the portion of Tablets taken:
Result = (rU/rS) × (CS/CU) × 100
| rU | = | = peak response of each individual impurity from the Sample solution |
| rS | = | = peak response of losartan from the Standard solution |
| CS | = | = concentration of USP Losartan Potassium RS in the Standard solution (mg/mL) |
| CU | = | = nominal concentration of losartan potassium in the Sample solution (mg/mL) |
Acceptance criteria:
See Table 3.
Table 3
| Name | Relative Retention Time |
Acceptance Criteria, NMT (%) |
|
|---|---|---|---|
| Losartan | 1.0 | — | |
| 1H-Dimera | 2.4 | 0.5 | |
| 2H-Dimerb | 2.9 | 0.5 | |
| Total impuritiesc | — | 1.0 | |
|
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 that are equal to or greater than 0.1%.
|
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ADDITIONAL REQUIREMENTS
• Packaging and Storage:
Store in tightly closed containers, protected from light, at controlled room temperature.
Add the following:
• Labeling:
When more than one Dissolution test is given, the labeling states the test used only if Test 1 is not used.(RB 1-Jul-2011)
• USP Reference Standards 11
11
USP Losartan Potassium RS 
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Auxiliary Information—
Please check for your question in the FAQs before contacting USP.
| Topic/Question | Contact | Expert Committee |
|---|---|---|
| Monograph | Sujatha Ramakrishna, Ph.D.
Senior Scientific Liaison 1-301-816-8349 |
(SM22010) Monographs - Small Molecules 2 |
| 711 |
Margareth R.C. Marques, Ph.D.
Senior Scientific Liaison 1-301-816-8106 |
(GCDF2010) General Chapters - Dosage Forms |
| Reference Standards | RS Technical Services 1-301-816-8129 rstech@usp.org |
USP35–NF30 Page 3723
Pharmacopeial Forum: Volume No. 36(2) Page 411