Rosiglitazone Maleate

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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C₁₈H₁₉N₃O₃S · C₄H₄O₄ 473.50

(±)-5-[p-[2-(Methyl-2-pyridylamino)ethoxy]benzyl]-2,4-thiazolidinedione maleate (1:1);

(RS)-5-{[4-({2-[Methyl(2-pyridinyl)amino]ethyl}oxy)phenyl]methyl}-1,3-thiazolidine-2,4-dione (Z)-2-butenedioate CAS RN^®: 155141-29-0; UNII: KX2339DP44.

1 DEFINITION

Rosiglitazone Maleate contains NLT 98.0% and NMT 102.0% of C₁₈H₁₉N₃O₃S · C₄H₄O₄, calculated on the anhydrous and solvent-free basis.

2 IDENTIFICATION

Change to read:

A. Spectroscopic Identification Tests 〈197〉, Infrared Spectroscopy: 197M (CN 1-May-2020)

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

3 ASSAY

3.1 Procedure

Buffer: Dissolve 5.75 g of phosphoric acid in 800 mL water, adjust with 4 N sodium hydroxide to a pH of 3.0, and dilute with water to 1 L.

Mobile phase: Acetonitrile and Buffer (25:75)

System suitability solution: Transfer 2.5 mg of USP Rosiglitazone Maleate RS and 1 mg of USP Rosiglitazone Related Compound A RS to a 50-mL volumetric flask, dissolve in 1 mL of stabilizer-free tetrahydrofuran, and dilute with Mobile phase to volume.

Standard solution: 0.05 mg/mL of USP Rosiglitazone Maleate RS in Mobile phase

Sample solution: 0.05 mg/mL of Rosiglitazone Maleate in Mobile phase

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 235 nm

Column: 4.6-mm × 25-cm; 5-µm packing L1

Column temperature: 40°

Flow rate: 1 mL/min

Injection size: 20 µL

System suitability

Samples: System suitability solution and Standard solution

Suitability requirements

Resolution: Greater than 2.0 between rosiglitazone and rosiglitazone related compound A, System suitability solution

Tailing factor: NMT 2.0, Standard solution

Relative standard deviation: NMT 1.0%, Standard solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of rosiglitazone maleate (C₁₈H₁₉N₃O₃S · C₄H₄O₄) in the portion of Rosiglitazone Maleate taken:

Result = (r_U/r_S) × (C_S/C_U) × 100

r_U = peak response from the Sample solution

r_S = peak response from the Standard solution

C_S = concentration of USP Rosiglitazone Maleate RS in the Standard solution (mg/mL)

C_U = concentration of Rosiglitazone Maleate in the Sample solution (mg/mL)

Acceptance criteria: 98.0%–102.0% on the anhydrous and solvent-free basis

4 OTHER COMPONENTS

4.1 Content of Maleic Acid

Buffer: Prepare 0.1 M sodium phosphate buffer as follows. Add 11.5 g of phosphoric acid to 800 mL of water, adjust with 2 N sodium hydroxide to a pH of 3.0, and dilute with water to 1 L.

Mobile phase: Methanol and Buffer (50:50)

Diluent: Methanol and water (50:50)

System suitability solution: 0.1 µg/mL of USP Fumaric Acid RS and 0.04 mg/mL of USP Rosiglitazone Maleate RS in Diluent

Standard solution: 0.01 mg/mL of USP Maleic Acid RS in Diluent

Sample solution: 0.04 mg/mL of Rosiglitazone Maleate in Diluent

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 212 nm

Column: 4.6-mm × 15-cm; 5-µm packing L14

Column temperature: 40°

Flow rate: 1.5 mL/min

Injection size: 20 µL

System suitability

Samples: System suitability solution and Standard solution

[Note—The relative retention times for rosiglitazone, maleic acid, and fumaric acid are 0.5, 1.0, and 1.8, respectively.]

Suitability requirements

Resolution: NLT 2.0 between maleic acid and fumaric acid, System suitability solution

Relative standard deviation: NMT 2.0%, Standard solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of maleic acid in the portion of Rosiglitazone Maleate taken:

Result = (r_U/r_S) × (C_S/C_U) × 100

r_U = peak response of maleic acid from the Sample solution

r_S = peak response of maleic acid from the Standard solution

C_S = concentration of USP Maleic Acid RS in the Standard solution (mg/mL)

C_U = concentration of Rosiglitazone Maleate in the Sample solution (mg/mL)

Acceptance criteria: 23.5%–26.0%

5 IMPURITIES

5.1 Residue on Ignition 〈281〉: NMT 0.2%, using an ignition temperature of 800 ± 25°

5.2 Organic Impurities

[Note—Protect the System suitability solution and Sample solution from light.]

Buffer 1: Prepare 0.05 M dibasic potassium phosphate buffer as follows. Dissolve 11.4 g of dibasic potassium phosphate trihydrate in 800 mL of water, adjust with a mixture of phosphoric acid and water (1:1) to a pH of 7.0, and dilute with water to 1 L.

Solution A: Acetonitrile and Buffer 1 (30:70)

Solution B: Acetonitrile and Buffer 1 (70:30)

Mobile phase: See Table 1. Return to original conditions and re-equilibrate the system.

Table 1

Buffer 2: Prepare 0.05 M monobasic potassium phosphate buffer by dissolving 6.8 g of monobasic potassium phosphate in 1 L of water.

Diluent: Acetonitrile and Buffer 2 (30:70)

System suitability solution: 0.5 mg/mL of USP Rosiglitazone Maleate RS in Diluent, using sonication, if necessary, to dissolve.

[Note—USP Rosiglitazone Maleate RS contains rosiglitazone related compound A as a minor component.]

Sample solution: 0.5 mg/mL of Rosiglitazone Maleate in Diluent, using sonication, if necessary, to dissolve

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 246 nm

Column: 4.6-mm × 25-cm; 5-µm packing L1

Flow rate: 1 mL/min

Injection size: 20 µL

System suitability

Sample: System suitability solution

[Note—Identify the peak due to rosiglitazone related compound A based on its relative retention time shown in Table 2.]

Suitability requirements

Resolution: NLT 2.0 between rosiglitazone and rosiglitazone related compound A

Analysis

Sample: Sample solution

Calculate the percentage of any individual impurity in the portion of Rosiglitazone Maleate taken:

Result = (r_U/r_T) × 100

r_U = peak response of each impurity from the Sample solution

r_T = sum of the peak responses from the Sample solution, except for the peak response of maleic acid

Acceptance criteria: See Table 2.

Table 2

ᵃ 2-(5-{[4-({2-[Methyl(2-pyridinyl)amino]ethyl}oxy)phenyl]methyl}-2,4-dioxo-1,3-thiazolidin-3-yl)butanedioic acid.

ᵇ 3-[4-({2-[Methyl(2-pyridinyl)amino]ethyl}oxy)phenyl]propanamide.

ᶜ (5Z)-5-{[4-({2-[Methyl(2-pyridinyl)amino]ethyl}oxy)phenyl]methylidene}-1,3-thiazolidine-2,4-dione.

6 SPECIFIC TESTS

Water Determination, Method Ia 〈921〉: NMT 0.5%

[Note—Because maleic acid will react with methanol thereby producing water, both titrant and solvent must be methanol free.]

7 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in tight containers, and store at room temperature.

USP Reference Standards 〈11〉

USP Fumaric Acid RS

USP Maleic Acid RS

USP Rosiglitazone Maleate RS

USP Rosiglitazone Related Compound A RS

(5Z)-5-{[4-({2-[Methyl(2-pyridinyl)amino]ethyl}oxy) phenyl]methylidene}-1,3-thiazolidine-2,4-dione.

C₁₈H₁₇N₃O₃S 355.41