Repaglinide 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

Repaglinide Tablets contain NLT 95.0% and NMT 105.0% of the labeled amount of repaglinide (C₂₇H₃₆N₂O₄).

2 IDENTIFICATION

A. Thin-Layer Chromatographic Identification Test 〈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)

Acceptance criteria: Meet the requirements

B. The retention time of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay.

C. The UV spectrum of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay.

3 ASSAY

Procedure

Buffer pH 4.0: 2 g/L of monobasic ammonium phosphate solution. Adjust with phosphoric acid to a pH of 4.0.

Buffer pH 2.5: 2 g/L of monobasic ammonium phosphate solution. Adjust with phosphoric acid to a pH of 2.5.

Mobile phase: Methanol and Buffer pH 2.5 (7:3)

Diluent: Methanol and Buffer pH 4.0 (7:3)

Standard solution 1: 800 µg/mL of USP Repaglinide RS in methanol

Standard solution 2: 80 µg/mL of USP Repaglinide RS, prepared by diluting 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: 80 µg/mL of USP Repaglinide RS and 1.6 µg/mL of USP Repaglinide Related Compound A RS prepared as follows. 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 or centrifuge a portion of the solution.

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 245 nm or diode array.

[Note—Use diode array detector to perform Identification test C.]

Column: 4.0-mm × 6-cm; 5-µm packing L1

Column temperature: 40°

Flow rate: 1 mL/min

Injection volume: 20 µL

System suitability

Samples: Standard solution 2 and System suitability solution

[Note—The typical relative retention times for repaglinide related compound A and repaglinide are about 0.4 and 1.0, respectively.]

Suitability requirements:

Resolution: NLT 7.0 between repaglinide related compound A and repaglinide, System suitability solution

Tailing factor: 0.8–2.0 for the repaglinide peak, 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 the labeled amount of repaglinide (C₂₇H₃₆N₂O₄) in the portion of Tablets taken:

Result = (rᵤ / rₛ) × (Cₛ / Cᵤ) × 100

rᵤ = peak response from the Sample solution

rₛ = peak response from Standard solution 2

Cₛ = concentration of USP Repaglinide RS in Standard solution 2 (µg/mL)

Cᵤ = nominal concentration of repaglinide in the Sample solution (µg/mL)

Acceptance criteria: 95.0%–105.0%

4 PERFORMANCE TESTS

Dissolution 〈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

Buffer: 1.5 g/L of monobasic potassium phosphate in water, adjusted with phosphoric acid to a pH of 2.3

Mobile phase: Acetonitrile, Buffer, and methanol (49:40:11)

Standard stock solution: 44 µg/mL of USP Repaglinide RS in methanol

Sample solution: Pass a portion of the solution under test through a suitable filter.

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. Further dilute with Medium, if needed, to a concentration that is similar to that of the Sample solution.

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 volume: 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: Sample solution and Standard solution

Calculate the percentage of the labeled amount of repaglinide (C₂₇H₃₆N₂O₄) 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 Repaglinide RS in the Standard solution (mg/mL)

L = label claim of repaglinide (mg/Tablet)

V = volume of Medium, 900 mL

Tolerances: NLT 70% (Q) of the labeled amount of repaglinide (C₂₇H₃₆N₂O₄) is dissolved.

Uniformity of Dosage Units 〈905〉

Meet the requirements.

5 IMPURITIES

Organic Impurities

Buffer pH 4.0, Buffer pH 2.5, Mobile phase, Diluent, 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: 0.2 µg/mL of USP Repaglinide RS, prepared by diluting 2.5 mL of Standard solution 2 with Diluent to 1000 mL

Chromatographic system

Mode: LC

Detector: UV 210 nm

Column: 4.0-mm × 6-cm; 5-µm packing L1

Column temperature: 40°

Flow rate: 1 mL/min

Injection volume: 20 µL

System suitability

Samples: System suitability solution and Standard solution 3

[Note—The typical relative retention times for repaglinide related compound A and repaglinide are about 0.4 and 1.0, respectively.]

Suitability requirements:

Resolution: NLT 7.0 between repaglinide related compound A and repaglinide, System suitability solution

Tailing factor: 0.8–2.0 for the repaglinide peak, System suitability solution

Relative standard deviation: NMT 10% for replicate injections, Standard solution 3

Analysis

Samples: Sample solution and Standard solution 3

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

Result = (rᵢ / rₛ) × (Cₛ / Cᵤ) × 100

rᵢ = peak response of each impurity from the Sample solution

rₛ = peak response of repaglinide from Standard solution 3

Cₛ = concentration of USP Repaglinide RS in Standard solution 3 (µg/mL)

Cᵤ = nominal concentration of repaglinide in the Sample solution (µg/mL)

Acceptance criteria: NMT 0.5% of total impurities

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in tight containers.

USP Reference Standards 〈11〉

USP Repaglinide RS

USP Repaglinide Related Compound A RS

(S)-3-Methyl-1-[2-(1-piperidinyl)phenyl]butylamine, N-acetyl-L-glutamate salt.

C₁₆H₂₆N₂ · C₅H₉NO₄ 435.6