Glimepiride Tablets
DEFINITION
Glimepiride Tablets contain NLT 90.0% and NMT 110.0% of the labeled amount of glimepiride (C24H34N4O5S).
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
[Note—Store the solutions containing glimepiride for NMT 24 h. ]
Mobile phase:
Dissolve 0.5 g of monobasic sodium phosphate in 500 mL of water. Adjust with 10% phosphoric acid to a pH of 2.1–2.7, and add 500 mL of acetonitrile.
Diluent:
Acetonitrile and water (9:1)
System suitability solution:
0.1 mg/mL of USP Glimepiride RS and 0.02 mg/mL each of USP Glimepiride Related Compound B RS and USP Glimepiride Related Compound C RS in Diluent
Standard solution:
0.1 mg/mL of USP Glimepiride RS in Diluent
Sample solution:
Transfer 5 whole Tablets into a suitable volumetric flask to prepare a solution of approximately 0.1 mg/mL of glimepiride, based on the label claim. Add water to 10% of the volume of the flask. Shake the flask to completely dissolve the Tablets. Add acetonitrile to about 70% of the volume of the flask, and swirl. Sonicate the samples in a water bath not to exceed 20
for NLT 5 min and NMT 10 min, with occasional shaking. Allow the solutions to come to room temperature, dilute with acetonitrile to volume, mix, and filter.
for NLT 5 min and NMT 10 min, with occasional shaking. Allow the solutions to come to room temperature, dilute with acetonitrile to volume, mix, and filter.
Chromatographic system
Mode:
LC
Detector:
UV 228 nm
Column:
4-mm × 12.5-cm; packing L1
Flow rate:
1 mL/min
Injection size:
10 µL
System suitability
Samples:
System suitability solution and Standard solution
[Note—The relative retention times for glimepiride related compound B, glimepiride related compound C, and glimepiride are 0.25, 0.35, and 1.0, respectively. Identify the glimepiride peak and the peaks due to the related compounds based on their relative retention times. ]
Suitability requirements
Resolution:
NLT 1.5 between glimepiride related compound B and glimepiride related compound C, System suitability solution
Tailing factor:
NMT 2.0 for the glimepiride peak, System suitability solution
Relative standard deviation:
NMT 2.0%, Standard solution
Analysis
Samples:
Standard solution and Sample solution
Calculate the percentage of the labeled amount of glimepiride (C24H34N4O5S) in the portion of Tablets taken:
Result = (rU/rS) × (CS/CU) × 100
| rU | = | = peak response from the Sample solution |
| rS | = | = peak response from the Standard solution |
| CS | = | = concentration of glimepiride in the Standard solution (mg/mL) |
| CU | = | = nominal concentration of glimepiride in the Sample solution (mg/mL) |
Acceptance criteria:
90.0%–110.0%
PERFORMANCE TESTS
• Dissolution 
711
711
Test 1
Medium:
pH 7.8 phosphate buffer (0.58 g of monobasic potassium phosphate and 8.86 g of dibasic sodium phosphate, anhydrous, in 1000 mL of water, adjusted with 10% phosphoric acid or 1 N sodium hydroxide to a pH of 7.8); 900 mL
Apparatus 2:
75 rpm
Time:
15 min
Mobile phase:
Prepare as directed in the Assay.
Diluting solution:
Methanol and water (1:1)
Standard solution:
Prepare a solution of USP Glimepiride RS in a mixture of acetonitrile and water (90:10) having a known concentration of about 0.125 mg/mL of glimepiride. Transfer 4.0 mL of this solution into a 200-mL volumetric flask, dilute with Medium to volume, and mix. Transfer 15.0 mL of this solution into a 50-mL volumetric flask, dilute with Diluting solution to volume, and mix. The final solution contains about 0.75 µg/mL of glimepiride.
Sample solution:
Withdraw approximately 10 mL of the solution under test, and transfer to a centrifuge tube. Centrifuge for 5 min at 2500 rpm. Pipet 3.0 mL of the supernatant into a 10-mL volumetric flask, dilute with Diluting solution to volume, and mix.
Chromatographic system
Mode:
LC
Detector:
UV 228 nm
Column:
4.0-mm × 12.5-cm; packing L1
Flow rate:
1.0 mL/min
Injection size:
50 µL
System suitability
Sample:
Standard solution
Suitability requirements
Tailing factor:
NMT 2.0
Relative standard deviation:
NMT 2.0%
Analysis:
Calculate the percentage of the labeled amount of glimepiride (C24H34N4O5S) 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 the Standard solution (mg/mL) |
| L | = | = label claim (mg/Tablet) |
| V | = | = volume of Medium, 900 mL |
Tolerances:
NLT 80% (Q) of the labeled amount of glimepiride (C24H34N4O5S) is dissolved.
Test 2:
If the product complies with this test, the labeling indicates that it meets USP Dissolution Test 2.
Medium:
pH 7.8 phosphate buffer (add 250 mL of 0.2 M monobasic potassium phosphate to 223 mL of 0.2 M sodium hydroxide, dilute with water to 1 L, and adjust with 0.2 M sodium hydroxide or phosphoric acid to a pH of 7.8); 900 mL
Apparatus 2:
75 rpm
Time:
45 min
Buffer solution:
4.0 g/L of ammonium acetate in water. Adjust with acetic acid to a pH of 5.3.
Mobile phase:
Acetonitrile and Buffer solution (1:1)
Diluent:
Methanol and acetonitrile (1:1)
Standard stock solution:
0.22 mg/mL of USP Glimepridie RS in Diluent
Standard solution:
(L/1000) mg/mL of USP Glimepiride RS in Medium, from the Standard stock solution, where L is the label claim in mg/Tablet
Sample solution:
Pass a portion of the solution under test through a suitable filter.
Chromatographic system
Mode:
LC
Detector:
UV 225 nm
Column:
4.6-mm × 10-cm; 5-µm packing L1
Flow rate:
1.3 mL/min
Injection size:
100 µL
System suitability
Sample:
Standard solution
Suitability requirements
Tailing factor:
NMT 2.0
Relative standard deviation:
NMT 2.0%
Analysis:
Calculate the percentage of the labeled amount of glimepiride (C24H34N4O5S) 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 the Standard solution (mg/mL) |
| L | = | = label claim (mg/Tablet) |
| V | = | = volume of Medium, 900 mL |
Tolerances:
NLT 80% (Q) of the labeled amount of glimepiride (C24H34N4O5S) is dissolved.
Test 3:
If the product complies with this test, the labeling indicates that it meets USP Dissolution Test 3.
Medium:
pH 7.8 phosphate buffer (prepared as indicated for Test 1); 900 mL
Apparatus 2:
75 rpm
Time:
20 min
Buffer solution:
1.36 g/L of monobasic potassium phosphate in water. Adjust with 10% sodium hydroxide to a pH of 7.0 ± 0.05.
Mobile phase:
Buffer solution and acetonitrile (675:325)
Standard stock solution:
0.22 mg/mL of USP Glimepiride RS in methanol
Standard solution:
(L/1000) mg/mL of glimepiride in Medium, from the Standard stock solution, where L is the label claim in mg/Tablet
Sample solution:
Pass a portion of the solution under test through a suitable filter.
Chromatographic system
Mode:
LC
Detector:
UV 228 nm
Column:
4.6-mm × 15-cm; 5-µm packing L1
Column temperature:
35
Flow rate:
1.5 mL/min
Injection size:
100 µL
System suitability
Sample:
Standard solution
Suitability requirements
Column efficiency:
NLT 2000 theoretical plates
Tailing factor:
NMT 2.0
Relative standard deviation:
NMT 2.0%
Analysis:
Calculate the percentage of the labeled amount of glimepiride (C24H34N4O5S) 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 the Standard solution (mg/mL) |
| L | = | = label claim (mg/Tablet) |
| V | = | = volume of Medium, 900 mL |
Tolerances:
NLT 80% (Q) of the labeled amount of glimepiride (C24H34N4O5S) is dissolved.
• Uniformity of Dosage Units 905:
Meet the requirements
905:
Meet the requirements
IMPURITIES
• Organic Impurities
[Note—Store the solutions containing glimepiride for NMT 24 h. ]
Mobile phase and Diluent:
Prepare as directed in the Assay.
System suitability solution:
4 µg/mL of USP Glimepiride RS and 2 µg/mL each of USP Glimepiride Related Compound B RS and USP Glimepiride Related Compound C RS in Diluent
Sensitivity solution:
Transfer 5.0 mL of the System suitability solution into a 100-mL volumetric flask, and dilute with Diluent to volume.
Sample solution:
Finely powder NLT 10 Tablets, and transfer a portion of the powder to a 50-mL centrifuge tube. Add Diluent to prepare a solution containing 0.1 mg/mL of glimepiride, based on the label claim. Sonicate in a water bath at a temperature not to exceed 20 for NLT 5 min and NMT 10 min, with occasional mixing. Centrifuge the samples, and use the clear supernatant.
for NLT 5 min and NMT 10 min, with occasional mixing. Centrifuge the samples, and use the clear supernatant.
Chromatographic system
Mode:
LC
Detector:
UV 228 nm
Column:
4-mm × 25-cm; packing L1
Flow rate:
1 mL/min
Injection size:
10 µL
System suitability
Samples:
System suitability solution and Sensitivity solution
[Note—The relative retention times for glimepiride related compound B, glimepiride related compound C, and glimepiride are 0.2, 0.3, and 1.0, respectively. Identify the glimepiride peak and the peaks due to the related compounds based on their relative retention times. ]
Suitability requirements
Resolution:
NLT 4 between glimepiride related compound B and glimepiride related compound C, System suitability solution
Relative standard deviation:
NMT 2.0% of the glimepiride peak, System suitability solution
Signal-to-noise ratio:
NLT 10, Sensitivity solution
Calculate the signal-to-noise ratio, S/N, for the peaks of glimepiride related compounds B and C:
Result = (2H)/h
| H | = | = measured height of the respective related compound peak |
| h | = | = amplitude of the average measured baseline noise |
Analysis
Samples:
Standard solution and Sample solution
[Note—Continue the elution for at least two times the retention time of the glimepiride peak. ]
Calculate the percentage of each impurity in the portion of Tablets taken:
Result = (rU/rT) × (1/F) × 100
| rU | = | = peak response for each impurity from the Sample solution |
| rT | = | = sum of all the peak responses from the Sample solution |
| F | = | = relative response factor: 1.3 for glimepiride related compound B, and 1.0 for any other impurity |
Acceptance criteria
Glimepiride related compound B:
NMT 2.5%
Any other individual impurity:
NMT 0.5%
Total impurities (excluding glimepiride related compound B) :
NMT 1.0%
Total impurities (including glimepiride related compound B):
NMT 3.5%
[Note—Disregard any peak less than 0.1%. ]
ADDITIONAL REQUIREMENTS
• Packaging and Storage:
Preserve in well-closed containers. Store at controlled room temperature.
• Labeling:
When more than one Dissolution test is given, the labeling states the Dissolution test used only if Test 1 is not used.
• USP Reference Standards 11
11
USP Glimepiride RS 
') + '&img=../../images/v35300/cas-93479-97-1.gif',600,500);)
USP Glimepiride Related Compound B RS
Glimepiride sulfonamide.
Glimepiride sulfonamide.
USP Glimepiride Related Compound C RS
Glimepiride urethane.
Glimepiride urethane.
Auxiliary Information—
Please check for your question in the FAQs before contacting USP.
| Topic/Question | Contact | Expert Committee |
|---|---|---|
| Monograph | Elena Gonikberg, Ph.D.
Principal Scientific Liaison 1-301-816-8251 |
(SM32010) Monographs - Small Molecules 3 |
| 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 3335
Pharmacopeial Forum: Volume No. 33(3) Page 411