Pioglitazone 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

Pioglitazone Tablets contain an amount of pioglitazone hydrochloride (C₁₉H₂₀N₂O₃S·HCI) equivalent to NLT 95.0% and NMT 105.0% of the labeled amount of pioglitazone (C₁₉H₂₀N₂O₃S).

2 IDENTIFICATION

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

B. ULTRAVIOLET ABSORPTION

Sample solution: Dissolve a quantity of finely powdered Tablets in 0.1 N hydrochloric acid to obtain a solution containing 25 µg/mL of pioglitazone. [NOTE-Vigorous shaking and filtration may be needed.]

Acceptance criteria: The UV absorption spectrum exhibits a maximum between 267 and 271 nm.

3 ASSAY

3.1 PROCEDURE

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

Standard solution: Prepare 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 the 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: Weigh and finely powder NLT 20 Tablets. Transfer an accurately weighed portion of the powder, equivalent to about 23 mg of pioglitazone, to a glass-stoppered flask, and add 50 mL of methanol. Disperse the particles by sonication for about 2 min, then centrifuge. Dilute a portion of the supernatant with Mobile phase to obtain a solution having a nominal concentration of 45 µg/mL of pioglitazone.

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: Standard solution and System suitability 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 the labeled amount of C₁₉H₂₀N₂O₃S in the portion of Tablets taken:

Result = (r_U/r_S) x (C_S/C_U) x (M_r1/M_r2) 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 = nominal concentration of pioglitazone in the Sample solution (µg/mL)

M_r1 = molecular weight of pioglitazone, 356.44

M_r2 = molecular weight of pioglitazone hydrochloride, 392.90

Acceptance criteria: 95.0%-105.0%

4 PERFORMANCE TESTS

4.1 DISSOLUTION (711)

Medium: Hydrochloric acid and potassium chloride buffer, pH 2.0 (mix 50 mL of 0.2 N hydrochloric acid and 150 mL of potassium chloride solution (150 mg/mL), dilute with water to 1 L, and adjust with 5 N hydrochloric acid to a pH of 2.0]; 900 mL

Apparatus 2: 75 rpm

Time: 15 min

Standard solution: Transfer 23 mg of USP Pioglitazone Hydrochloride RS to a 50-mL volumetric flask, dissolve in 10 mL of methanol, and dilute with Medium to volume. Dilute this solution with Medium to obtain a final concentration of about L/900, where L is the label claim (mg).

Sample solution: Pass a portion of the solution under test through a suitable filter of 0.45-µm pore size.

Detector: UV

Analytical wavelength: 269 nm

Cell: 1 cm

Blank: Medium

Calculate the percentage of pioglitazone dissolved:

Result = (A_U/A_S) x (C_S/L) x (M_r1/M_r2) x V x 100

A_U = absorbance of the Sample solution

A_S = absorbance of the Standard solution

C_S = concentration of the Standard solution (mg/mL)

L = Tablet label claim (mg)

M_r1 = molecular weight of pioglitazone, 356.44

M_r2 = molecular weight of pioglitazone hydrochloride, 392.90

V = volume of Medium (mL), 900

Tolerances: NLT 80% (Q) of the labeled amount of pioglitazone is dissolved.

4.2 UNIFORMITY OF DOSAGE UNITS (905)

Meet the requirements

Procedure for content uniformity

Standard solution: 26 µg/mL of USP Pioglitazone Hydrochloride RS in methanol and 0.1 N hydrochloric acid (9:1)

Sample solution: Transfer 1 Tablet to an appropriate size volumetric flask such that the final concentration does not exceed 0.3 mg of pioglitazone per mL. Add 0.1 N hydrochloric acid at a volume equivalent to 10% of the total volume and shake until the Tablet is completely disintegrated. Add methanol at a volume equivalent to 70% of the total volume and shake vigorously for 10 min. Dilute with methanol to volume, mix well, and centrifuge. Dilute a portion of the supernatant with methanol and 0.1 N hydrochloric acid (9:1) to obtain a solution having a concentration of 24 µg/mL of pioglitazone.

Spectrometric conditions

(See Ultraviolet-Visible Spectroscopy (857).)

Mode: UV-Vis

Analytical wavelength: 269 nm

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of C₁₉H₂₀N₂O₃S in the Tablet taken:

Result = (A_U/A_S) x (C_S/C_U) x (M_r1/M_r2) x 100

A_U = absorbance of the Sample solution

A_S = absorbance of the Standard solution

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

C_U = nominal concentration of pioglitazone in the Sample solution (µg/mL)

M_r1 = molecular weight of pioglitazone, 356.44

M_r2 = molecular weight of pioglitazone hydrochloride, 392.90

5 IMPURITIES

ORGANIC IMPURITIES

PROCEDURE

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

Diluent: Mobile phase and methanol (4:1)

Standard solution: 1 µg/mL of USP Pioglitazone Hydrochloride RS in Diluent. [NOTE-If necessary, dissolve USP Pioglitazone Hydrochloride RS in a minimal amount of methanol and then dilute with Diluent to final concentration.]

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: Weigh and finely powder 20 Tablets. Transfer an accurately weighed portion of the powder, equivalent to about 18 mg of pioglitazone, to a 100-mL volumetric flask and add 20 mL of methanol. Disperse the particles by sonication for about 1 min, then dilute with Mobile phase to volume, mix well, centrifuge, and use the supernatant.

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.]

Run time: At least 30 min

Injection size: 40 μL

System suitability

Samples: Standard solution and System suitability 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

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

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

Result = (r_U/r_S) x (C_S/C_U) x (M_r1/M_r2) x 100

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

r_S = peak response of pioglitazone from the Standard solution

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

C_U = nominal concentration of pioglitazone in the Sample solution (µg/mL)

M_r1 = molecular weight of pioglitazone, 356.44

M_r2 = molecular weight of pioglitazone hydrochloride, 392.90

Acceptance criteria

Individual impurities: NMT 0.2%

Total impurities: NMT 0.6%

6 ADDITIONAL REQUIREMENTS

6.1 PACKAGING AND STORAGE

Preserve in tight containers and store at controlled room temperature.

6.2 USP REFERENCE STANDARDS (11)

USP Pioglitazone Hydrochloride RS