Repaglinide Tablets
DEFINITION
Repaglinide Tablets contain NLT 95.0% and NMT 105.0% of the labeled amount of repaglinide (C27H36N2O4).
IDENTIFICATION
• A. Thin-Layer Chromatographic Identification Test 
201
201
Sample solution:
To a quantity of powdered Tablets, equivalent to 10 mg of repaglinide, add 10 mL of a mixture of methanol and methylene chloride (1:1), shake for 15 min, and centrifuge.
Developing solvent system:
Toluene, methylene chloride, and methanol (2:2:1)
• B.
The retention time and UV spectrum of the major peak of the Sample solution correspond to those of the Standard solution, as obtained in the Assay.
ASSAY
• Procedure
Solution A:
Monobasic ammonium phosphate solution (2 in 1000). Adjust with phosphoric acid to a pH of 4.0.
Solution B:
Monobasic ammonium phosphate solution (2 in 1000). Adjust with phosphoric acid to a pH of 2.5.
Diluent:
Methanol and Solution A (7:3)
Mobile phase:
Methanol and Solution B (7:3)
Standard solution 1:
800 µg/mL of USP Repaglinide RS in methanol
Standard solution 2:
Dilute 5.0 mL of Standard solution 1 with Diluent to 50.0 mL.
System suitability stock solution:
80 µg/mL of USP Repaglinide Related Compound A RS in methanol
System suitability solution:
Transfer 1.0 mL of System suitability stock solution to a 50-mL volumetric flask, add 5.0 mL of Standard solution 1, and dilute with Diluent to volume.
Sample solution:
Transfer 8 whole Tablets to a suitable volumetric flask, and dissolve in and dilute with Diluent to volume to obtain a solution containing 80 µg/mL. Stir for 20 min, and filter a portion of the solution.
Chromatographic system
Mode:
LC
Detector:
245-nm diode array
Column:
4.0-mm × 6-cm; 5-µm packing L1
Column temperature:
40
Flow rate:
1 mL/min
Injection size:
20 µL
System suitability
Samples:
Standard solution 2 and System suitability solution
Suitability requirements
Resolution:
NLT 7.0 between repaglinide and repaglinide related compound A, System suitability solution
Capacity factors, k¢:
For repaglinide and repaglinide related compound A, about 4.9 and 1.2, respectively, System suitability solution
Tailing factor:
0.8–2.0, System suitability solution
Relative standard deviation:
NMT 2.0% for replicate injections, Standard solution 2
Analysis
Samples:
Standard solution 2 and Sample solution
Calculate the percentage of C27H36N2O4 in the portion of Tablets taken:
Result = (rU/rS) × (CS/CU) × 100
| rU | = | = peak response of the Sample solution |
| rS | = | = peak response of the Standard solution 2 |
| CS | = | = concentration of USP Repaglinide RS in Standard solution 2 (mg/mL) |
| CU | = | = nominal concentration of repaglinide in the Sample solution (mg/mL) |
Acceptance criteria:
95.0%–105.0%
PERFORMANCE TESTS
• Dissolution 711
711
Medium:
pH 5.0 buffer, prepared by mixing 10.2 g of citric acid monohydrate and 18.16 g of dibasic sodium phosphate dihydrate with 1 L of water; 900 mL
Apparatus 2:
75 rpm
Time:
30 min
Solution A:
Monobasic potassium phosphate solution (1.5 in 1000), adjusted with phosphoric acid to a pH of 2.3
Mobile phase:
Acetonitrile, Solution A, and methanol (49:40:11)
Standard stock solution:
11 µg/mL of USP Repaglinide RS in methanol
Standard solution:
Transfer 5.0 mL of the Standard stock solution to a 100-mL volumetric flask, add 25 mL of methanol, and dilute with Medium to volume.
Sample solution:
Pass a portion of the solution under test through a suitable filter.
Determine the amount of C27H36N2O4 dissolved by using the following method.
Chromatographic system
Mode:
LC
Detector:
Fluorometric detector; excitation wavelength of 244 nm and emission wavelength of 348 nm
Column:
4.0-mm × 12.5-cm; 10-µm packing L1
Column temperature:
40
Flow rate:
1 mL/min
Injection size:
20 µL
System suitability
Sample:
Standard solution
Suitability requirements
Tailing factor:
Between 0.5 and 2.0
Relative standard deviation:
NMT 2.0%
Analysis
Samples:
Standard solution and Sample solution
Calculate the quantity of C27H36N2O4 dissolved by comparing the measured peak responses from the Standard solution and the Sample solution.
Tolerances:
NLT 70% (Q) of the labeled amount of C27H36N2O4 is dissolved.
• Uniformity of Dosage Units 905:
Meet the requirements
905:
Meet the requirements
IMPURITIES
Organic Impurities
• Procedure
Solution A, Solution B, Diluent, Mobile phase, Standard solution 1, Standard solution 2, System suitability stock solution, System suitability solution, and Sample solution:
Prepare as directed in the Assay.
Standard solution 3:
Dilute 2.5 mL of Standard solution 2 with Diluent to 1000 mL.
Chromatographic system
Mode:
LC
Detector:
210-nm diode array
Column:
4.0-mm × 6-cm; 5-µm packing L1
Column temperature:
40
Flow rate:
1 mL/min
Injection size:
20 µL
System suitability
Samples:
Standard solution 3 and System suitability solution
Suitability requirements
Resolution:
NLT 7.0 between repaglinide and repaglinide related compound A, System suitability solution
Capacity factors, k¢:
For repaglinide and repaglinide related compound A, about 4.9 and 1.2, respectively, System suitability solution
Tailing factor:
0.8–2.0, System suitability solution
Relative standard deviation:
NMT 10% for replicate injections, Standard solution 3
Analysis
Samples:
Standard solution 2 and Sample solution
Calculate the percentage of each impurity in the portion of Tablets taken:
Result = (rU/rS) × 100
| rU | = | = peak response of each impurity from the Sample solution |
| rS | = | = peak response of repaglinide from the Standard solution 2 |
Acceptance criteria:
NMT 0.5% of total impurities
ADDITIONAL REQUIREMENTS
• Packaging and Storage:
Preserve in tight containers.
• USP Reference Standards 11
11
USP Repaglinide RS 
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USP Repaglinide Related Compound A RS
(S)-3-Methyl-1-[2-(1-piperidinyl)phenyl]butylamine,N-acetyl-l-glutamate salt.
C16H26N2·C7H11NO5 435.6
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(S)-3-Methyl-1-[2-(1-piperidinyl)phenyl]butylamine,N-acetyl-l-glutamate salt.
C16H26N2·C7H11NO5 435.6
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 4531
Pharmacopeial Forum: Volume No. 35(2) Page 306