Glyburide Tablets
DEFINITION
Glyburide Tablets contain NLT 90.0% and NMT 110.0% of the labeled amount of glyburide (C23H28ClN3O5S).
IDENTIFICATION
• Infrared Absorption 
197K
197K
Sample:
Grind to a fine powder a number of Tablets, equivalent to 15 mg of glyburide. Add 30 mL of acetonitrile, and shake. Filter the mixture, evaporate the filtrate to dryness, and dry the residue in a vacuum at 60
for 3 h.
for 3 h.
ASSAY
• Procedure
Mobile phase:
Dissolve 2.6 g of monobasic ammonium phosphate in 450 mL of water. Add 550 mL of acetonitrile, filter, and degas. Adjust, if necessary, with phosphoric acid or sodium hydroxide to a pH of 5.25 ± 0.30.
Progesterone solution:
0.2 mg/mL of progesterone in acetonitrile
System suitability solution:
Dissolve 10 mg of USP Glyburide RS in 20 mL of Progesterone solution. Add 4.0 mL of water.
Standard solution:
To 10 mg of USP Glyburide RS add 20.0 mL of acetonitrile, and shake vigorously to dissolve. Add 4.0 mL of water.
Sample solution:
Transfer NLT 20 Tablets to a suitable container. Add water equivalent to 0.4 mL of water per mg of glyburide, and swirl to disperse and wet Tablet material. Then add acetonitrile equivalent to 2.0 mL of acetonitrile per mg of glyburide, and shake for 30 min. Centrifuge a portion of the suspension, and use the clear supernatant.
Chromatographic system
Mode:
LC
Detector:
UV 254 nm
Column:
4.6-mm × 25-cm; packing L7
Flow rate:
2 mL/min
Injection size:
10 µL
System suitability
Sample:
System suitability solution
[Note—The relative retention times for glyburide and progesterone are about 0.4 and 1.0, respectively. ]
Suitability requirements
Resolution:
NLT 5.0 between glyburide and progesterone
Relative standard deviation:
NMT 2.0% for glyburide
Analysis
Samples:
Standard solution and Sample solution
Calculate the percentage of glyburide (C23H28ClN3O5S) 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 USP Glyburide RS in the Standard solution (mg/mL) |
| CU | = | = nominal concentration of glyburide in the Sample solution (mg/mL) |
Acceptance criteria:
90.0%–110.0%
PERFORMANCE TESTS
• Dissolution 711
711
Test 1 (nonmicronized glyburide)
Medium:
0.05 M borate buffer, pH 9.5 (381.5 g of sodium borate and 19.1 g of sodium hydroxide in 20 L of water, and adjust with phosphoric acid to a pH of 9.5 ± 0.1); 500 mL
Apparatus 2:
75 rpm
Time:
45 min. [Note—Use low-actinic volumetric flasks. ]
Mobile phase:
Acetonitrile and water (1:1), containing 4.0 mL of phosphoric acid per L of solution
Standard stock solution:
0.15 mg/mL of USP Glyburide RS in Medium. [Note—Sonicate for about 25 min to dissolve, and dilute with Medium to volume. ]
Standard solutions:
Dilute the Standard stock solution with Medium to obtain 0.003 mg/mL (for Tablets labeled to contain 1.5 mg), 0.006 mg/mL (for Tablets labeled to contain 3.0 mg), 0.009 mg/mL (for Tablets labeled to contain 4.5 mg), and 0.012 mg/mL (for Tablets labeled to contain 6.0 mg).
Sample solution:
Pass a portion of the solution under test through a suitable filter of 0.45-µm pore size.
Chromatographic system
Mode:
LC
Detector:
UV 215 nm
Column:
4.6-mm × 30-cm; 10-µm packing L1
Flow rate:
2 mL/min
Injection size:
50 µL
System suitability
Sample:
Standard solution
Suitability requirements
Column efficiency:
NLT 4000 theoretical plates
Tailing factor:
NMT 2.0
Relative standard deviation:
NMT 3.0%
Analysis
Samples:
Standard solution and Sample solution
Determine the percentage of glyburide (C23H28ClN3O5S) 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 | = | = Tablet label claim (mg) |
| V | = | = volume of Medium, 500 mL |
Tolerances:
NLT 70% (Q) of the labeled amount of glyburide (C23H28ClN3O5S) is dissolved.
Test 2 (micronized glyburide):
If the product complies with this test, the labeling indicates that it meets USP Dissolution Test 2.
Medium:
0.05 M phosphate buffer, pH 8.5 (6.8 g of monobasic potassium phosphate and 1.99 g of sodium hydroxide in 1 L of water, and adjust with diluted phosphoric acid or diluted sodium hydroxide to a pH of 8.5 ± 0.05); 900 mL
Apparatus 2:
50 rpm
Time:
30 min
Mobile phase:
Acetonitrile and water containing 5 g/L of monobasic ammonium phosphate (480:520)
Standard stock solution:
Transfer 67 mg of USP Glyburide RS to a 500-mL volumetric flask, dissolve in 40 mL of methanol with sonication for 5 min, and dilute with Medium to volume.
Standard solutions:
Dilute the Standard stock solution with Medium to obtain solutions having known concentrations of 0.0017 mg/mL (for Tablets labeled to contain 1.5 mg), 0.0034 mg/mL (for Tablets labeled to contain 3 mg), 0.0047 mg/mL (for Tablets labeled to contain 4.5 mg), and 0.0067 mg/mL (for Tablets labeled to contain 6 mg).
Sample solution:
Pass a portion of the solution under test through a suitable filter of 0.5-µm pore size.
Chromatographic system
Mode:
LC
Detector:
UV 215 nm
Column:
4.0-mm × 25-cm; 10-µm packing L7
Flow rate:
1.5 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
Samples:
Standard solution and Sample solution
Determine the percentage of glyburide (C23H28ClN3O5S) 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 | = | = Tablet label claim (mg) |
| V | = | = volume of Medium, 900 mL |
Tolerances:
NLT 75% (Q) of the labeled amount of glyburide (C23H28ClN3O5S) is dissolved.
Test 3 (micronized glyburide):
If the product complies with this test, the labeling indicates that it meets USP Dissolution Test 3.
Medium:
0.05 M phosphate buffer, pH 7.5 (40.8 g of monobasic potassium phosphate and 9.4 g of sodium hydroxide, in 6 L of water, and adjust with diluted sodium hydroxide to a pH of 7.5 ± 0.1); 900 mL
Apparatus 2:
50 rpm
Time:
45 min
Mobile phase:
Proceed as directed in the Assay.
Diluent:
Acetonitrile and water (5:1)
Standard stock solution:
0.67 mg/mL of USP Glyburide RS in Diluent
Standard solution:
6.7 µg/mL of USP Glyburide RS in Medium from Standard stock solution
Sample solution:
Pass a portion of the solution under test through a suitable filter of 0.45-µm pore size.
Chromatographic system
Mode:
LC
Detector:
UV 254 nm
Column:
4.6-mm × 25-cm; packing L7
Flow rate:
2 mL/min
Injection size:
75 µL
System suitability
Sample:
Standard solution
Suitability requirements
Relative standard deviation:
NMT 2.0%
Analysis
Samples:
Standard solution and Sample solution
Determine the percentage of glyburide (C23H28ClN3O5S) 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 | = | = Tablet label claim (mg) |
| V | = | = volume of Medium, 900 mL |
Tolerances:
NLT 75% (Q) of the labeled amount of glyburide (C23H28ClN3O5S) is dissolved.
Test 4 (nonmicronized glyburide):
If the product complies with this test, the labeling indicates that it meets USP Dissolution Test 4.
Medium:
0.05 M borate buffer, pH 8.0, with 0.014 M hexadecyltrimethylammonium bromide (prepared by dissolving about 180.0 g of hexadecyltrimethylammonium bromide, 55.6 g of boric acid, 67.1 g of potassium chloride, and 2.8 g of sodium hydroxide in 1500 mL of water at 50 under vigorous stirring for several hours, cooling to room temperature, diluting with water to 2000 mL, adjusting with diluted hydrochloride acid or diluted sodium hydroxide to a pH of 8.00 ± 0.05, and diluting 50 mL of this solution with water to 900 mL); 900 mL
under vigorous stirring for several hours, cooling to room temperature, diluting with water to 2000 mL, adjusting with diluted hydrochloride acid or diluted sodium hydroxide to a pH of 8.00 ± 0.05, and diluting 50 mL of this solution with water to 900 mL); 900 mL
Apparatus 1:
50 rpm
Time:
45 min
Mobile phase:
Acetonitrile and water (11:9) containing 5.2 g of monobasic ammonium phosphate for each 2 L
Standard stock solution:
0.27 mg/mL of USP Glyburide RS in alcohol. Transfer 1.0 mL of this solution to a 100-mL volumetric flask, and dilute with Medium to volume.
Standard solution:
2.8 µg/mL of USP Glyburide RS in Medium, from the Standard stock solution
Sample solution:
Pass a portion of the solution under test through a suitable filter of 5-µm pore size.
Chromatographic system
Mode:
LC
Detector:
UV 226 nm
Column:
4.6-mm × 25-cm; packing L7
Flow rate:
2 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
Samples:
Standard solution and Sample solution
Determine the percentage of glyburide (C23H28ClN3O5S) 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 | = | = Tablet label claim (mg) |
| V | = | = volume of Medium, 900 mL |
Tolerances:
NLT 75% (Q) of the labeled amount of glyburide (C23H28ClN3O5S) is dissolved.
Test 5 (micronized glyburide):
If the product complies with this test, the labeling indicates that it meets USP Dissolution Test 5.
Medium:
0.05 M phosphate buffer, pH 7.5 (40.8 g of monobasic potassium phosphate and 9.4 g of sodium hydroxide, in 6 L of water, and adjust with diluted sodium hydroxide to a pH of 7.5 ± 0.1); 900 mL
Apparatus 2:
50 rpm
Time:
30 min
Standard solution:
USP Glyburide RS in Medium in a concentration similar to the one expected in the Sample solution
Sample solution:
Pass a portion of the solution under test through a suitable filter. Dilute with Medium, if necessary.
Mobile phase, Diluent, Chromatographic system, System suitability, and Analysis:
Proceed as directed for Test 3.
Tolerances:
NLT 75% (Q) of the labeled amount of glyburide (C23H28ClN3O5S) is dissolved.
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 Glyburide RS 
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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 3348
Pharmacopeial Forum: Volume No. 33(4) Page 651