Pioglitazone Tablets
DEFINITION
Pioglitazone Tablets contain an amount of pioglitazone hydrochloride (C19H20N2O3S·HCl) equivalent to NLT 95.0% and NMT 105.0% of the labeled amount of pioglitazone (C19H20N2O3S).
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.
ASSAY
•  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.
Chromatographic system 
Mode:  LC
Detector:  UV 269 nm
Column:  4.6-mm × 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
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
Analysis 
Samples:  Standard solution and Sample solution
Calculate the percentage of the labeled amount of C19H20N2O3S in the portion of Tablets taken:
Result = (rU/rS) × (CS/CU) × (Mr1/Mr2) × 100
rU== peak response from the Sample solution
rS== peak response from the Standard solution
CS== concentration of USP Pioglitazone Hydrochloride RS in the Standard solution (µg/mL)
CU== nominal concentration of pioglitazone in the Sample solution (µg/mL)
Mr1== molecular weight of pioglitazone, 356.44
Mr2== molecular weight of pioglitazone hydrochloride, 392.90
Acceptance criteria:  95.0%–105.0%
PERFORMANCE TESTS
•  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 = (AU/AS) × (CS/L) × (Mr1/Mr2) × V × 100
AU== absorbance of the Sample solution
AS== absorbance of the Standard solution
CS== concentration of the Standard solution (mg/mL)
L== Tablet label claim (mg)
Mr1== molecular weight of pioglitazone, 356.44
Mr2== 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.
•  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 
Mode:  UV-Vis
Analytical wavelength:  269 nm
Analysis 
Samples:  Standard solution and Sample solution
Calculate the percentage of C19H20N2O3S in the Tablet taken:
Result = (AU/AS) × (CS/CU) × (Mr1/Mr2) × 100
AU== absorbance of the Sample solution
AS== absorbance of the Standard solution
CS== concentration of USP Pioglitazone Hydrochloride RS in the Standard solution (µg/mL)
CU== nominal concentration of pioglitazone in the Sample solution (µg/mL)
Mr1== molecular weight of pioglitazone, 356.44
Mr2== molecular weight of pioglitazone hydrochloride, 392.90
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 
Mode:  LC
Detector:  UV 269 nm
Column:  4.6-mm × 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 = (rU/rS) × (CS/CU) × (Mr1/Mr2) × 100
rU== peak response of each individual impurity from the Sample solution
rS== peak response of pioglitazone from the Standard solution
CS== concentration of USP Pioglitazone Hydrochloride RS in the Standard solution (µg/mL)
CU== nominal concentration of pioglitazone in the Sample solution (µg/mL)
Mr1== molecular weight of pioglitazone, 356.44
Mr2== molecular weight of pioglitazone hydrochloride, 392.90
Acceptance criteria 
Individual impurities:  NMT 0.2%
Total impurities:  NMT 0.6%
ADDITIONAL REQUIREMENTS
•  Packaging and Storage: Preserve in tight containers and store at controlled room temperature.
•  USP Reference Standards 11
USP Pioglitazone Hydrochloride RS Click to View Structure
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
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USP35–NF30 Page 4330
Pharmacopeial Forum: Volume No. 36(1) Page 128