Pioglitazone Hydrochloride

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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C₁₉H₂₀N₂O₃S·HCI 392.90

2,4-Thiazolidinedione, 5-[[4-[2-(5-ethyl-2-pyridinyl)ethoxyphenyl]methyl]-, monohydrochloride, (±)-;

(±)-5-[p-[2-(5-Ethyl-2-pyridyl)ethoxy]benzyl]-2,4-thiazolidinedione monohydrochloride CAS RN^®: 112529-15-4; UNII: JQT35NPK6C.

1 DEFINITION

Pioglitazone Hydrochloride contains NLT 98.0% and NMT 102.0% of C₁₉H₂₀N₂O₃S·HCI, calculated on the anhydrous basis.

2 IDENTIFICATION

Change to read:

A. SPECTROSCOPIC IDENTIFICATION TESTS (197), Infrared Spectroscopy: 197K (CN 1-MAY-2020)

B. IDENTIFICATION TESTS-GENERAL, Chloride (191); Dissolve 25 mg of Pioglitazone Hydrochloride in 0.5 mL of nitric acid, and add 2 mL of dilute nitric acid. It meets the requirements of the test for Chloride.

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

3 ASSAY

3.1 PROCEDURE

Mobile phase: Acetonitrile, 0.1 M ammonium acetate, and glacial acetic acid (25:25:1)

Standard solution: Prepare a 0.5 mg/mL solution of USP Pioglitazone Hydrochloride RS in methanol, and dilute with Mobile phase to obtain a solution containing 50 µg/mL of pioglitazone hydrochloride.

System suitability stock solution: 0.5 mg/mL of USP Pioglitazone Hydrochloride RS and 0.13 mg/mL of benzophenone in methanol

System suitability solution: Dilute System suitability stock solution with Mobile phase to obtain a solution containing 50 µg/mL of pioglitazone hydrochloride and 13 µg/mL of benzophenone.

Sample solution: Prepare a 0.5 mg/mL solution of pioglitazone hydrochloride in methanol, and dilute with Mobile phase to obtain a solution containing 50 µg/mL of pioglitazone hydrochloride.

3.2 Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 269 nm

Column: 4.6-mm x 15-cm; 5-µm packing L1

Column temperature: 25 ± 2.5°

Flow rate: 0.7 mL/min

[NOTE-Adjust the flow rate so that the retention time of the pioglitazone peak is about 7 min.]

Injection size: 20 µL

3.3 System suitability

Samples: System suitability solution and Standard solution

[NOTE-The approximate relative retention times for pioglitazone and benzophenone are 1.0 and 2.6, respectively.]

Suitability requirements

Tailing factor: NMT 1.5 for pioglitazone and benzophenone, System suitability solution

Resolution: NLT 15 between pioglitazone and benzophenone, System suitability solution

Relative standard deviation: NMT 2.0% for six replicate injections, Standard solution

3.4 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of C₁₉H₂₀N₂O₃S·HCI in the portion of Pioglitazone Hydrochloride taken:

Result = (r_U/r_S) x (C_S/C_U) x 100

r_U = peak response from the Sample solution

r_S = peak response from the Standard solution

C_S = concentration of USP Pioglitazone Hydrochloride RS in the Standard solution (µg/mL)

C_U = concentration of Pioglitazone Hydrochloride in the Sample solution (µg/mL)

Acceptance criteria: 98.0%-102.0% on the anhydrous basis

4 IMPURITIES

4.1 INORGANIC IMPURITIES

RESIDUE ON IGNITION (281): NMT 0.1%

4.2 ORGANIC IMPURITIES

PROCEDURE

Mobile phase and System suitability stock solution: Proceed as directed in the Assay.

System suitability solution: Dilute the System suitability stock solution with Mobile phase to obtain a solution containing 25 µg/mL of pioglitazone hydrochloride and 6.5 µg/mL of benzophenone.

Sample solution: 0.2 mg/mL of pioglitazone hydrochloride dissolved in 20% of the final volume with methanol, then diluted with Mobile phase to final volume

Standard solution: 1 µg/mL of pioglitazone hydrochloride prepared by diluting the Sample solution with Mobile phase

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 269 nm

Column: 4.6-mm x 15-cm; 5-µm packing L1

Column temperature: 25 ± 2.5°

Flow rate: 0.7 mL/min

[NOTE-Adjust the flow rate so that the retention time of the pioglitazone peak is about 7 min.]

Injection size: 40 µL

Run time: At least four times the retention time of pioglitazone

System suitability

Samples: System suitability solution and Standard solution

Suitability requirements

Tailing factor: NMT 1.5 for pioglitazone and benzophenone, System suitability solution

Resolution: NLT 15 between pioglitazone and benzophenone, System suitability solution

Relative standard deviation: NMT 3.0%, Standard solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of each impurity in the portion of Pioglitazone Hydrochloride taken:

Result = (r_U/r_S) x D x 100

r_U = peak response of each individual impurity from the Sample solution

r_S = peak response of pioglitazone from the Standard solution

D = dilution factor used to prepare the Standard solution, 0.005

Acceptance criteria

Individual impurities: See Impurity Table 1.

Total impurities: NMT 0.5%

Impurity Table 1

^a (±)-5-{4-[2-(5-Ethylpyridin-2-yl)ethoxy]benzyl}-5-hydroxythiazolidine-2,4-dione.

^b (Z)-5-{4-[2-(5-Ethylpyridin-2-yl)ethoxy]benzylidene}thiazolidine-2,4-dione.

^c (±)-5-{4-[2-(5-Ethylpyridin-2-yl)ethoxy]benzyl}-3-[2-(5-ethylpyridin-2-yl)ethyl]thiazolidine-2,4-dione.

5 SPECIFIC TESTS

WATER DETERMINATION, Method Ic (921): NMT 0.5%

6 ADDITIONAL REQUIREMENTS

6.1 PACKAGING AND STORAGE

Preserve in well-closed containers, and store at room temperature.

6.2 USP REFERENCE STANDARDS (11)

USP Pioglitazone Hydrochloride RS