Ezetimibe 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

Ezetimibe Tablets contain NLT 93.0% and NMT 107.0% of the labeled amount of ezetimibe (C₂₄H₂₁F₂NO₃).

2 IDENTIFICATION

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

B. The UV absorption spectrum of the ezetimibe peak of the Sample solution exhibits maxima and minima at the same wavelengths as those of the corresponding peak of the Standard solution, as obtained in the Assay.

3 ASSAY

3.1 Procedure

Buffer: Dissolve 6.8 g of monobasic potassium phosphate in 1 L of water.

Mobile phase: Tetrahydrofuran, acetonitrile, and Buffer (100:250:650)

Diluent: Acetonitrile, glacial acetic acid, and water (600:1:400)

Standard solution: 0.2 mg/mL of USP Ezetimibe RS in Diluent. Pass through a suitable filter of 0.45-μm pore size and discard the first 3 mL of the filtrate.

Sample solution: Nominally 0.2 mg/mL of ezetimibe in Diluent prepared as follows. Place NLT 10 powdered Tablets in a suitable volumetric flask, add Diluent to fill about 60% of the total volume, sonicate for about 30 min, and shake on a wrist shaker for about 45 min. Dilute with Diluent to volume, pass through a suitable filter of 0.45-μm pore size, and discard the first 3 mL of the filtrate.

3.2 Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 232 nm. For Identification B, use a diode array detector in the range of 200–400 nm.

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

Flow rate: 1 mL/min

Injection volume: 30 μL

Run time: NLT 2.4 times the retention time of the ezetimibe peak

3.3 System suitability

Sample: Standard solution

3.4 Suitability requirements

Tailing factor: NMT 1.5

Relative standard deviation: NMT 1.0%

3.5 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of ezetimibe (C₂₄H₂₁F₂NO₃) in the portion of Tablets taken:

Result = (r_U /r_S ) × (C_S /C_U ) × 100

r_U = peak response of ezetimibe from the Sample solution

r_S = peak response of ezetimibe from the Standard solution

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

C_U = nominal concentration of ezetimibe in the Sample solution (mg/mL)

Acceptance criteria: 93.0%–107.0%

4 PERFORMANCE TESTS

Dissolution 〈711〉

Test 1

Do not refrigerate solutions containing ezetimibe.

Medium: 0.45% sodium lauryl sulfate in 0.05 M sodium acetate buffer, pH 4.5, prepared as follows. To 6 L of water in a suitable flask, add about 27 g of sodium lauryl sulfate and 24.6 g of sodium acetate. Dissolve the reagents by stirring until the solution is clear. Adjust with either hydrochloric acid or sodium hydroxide to a pH of 4.5; 500 mL.

Apparatus 2: 50 rpm

Time: 30 min

Standard solution: 0.02 mg/mL of USP Ezetimibe RS in Medium prepared as follows. To a suitable amount of USP Ezetimibe RS in an appropriate volumetric flask, add methanol to fill about 1% of the total volume, and shake until completely dissolved. Dilute with Medium to volume.

Sample solution: Pass a portion of the solution under test through a suitable filter of 0.45-μm pore size. Discard the first 3 mL of the filtrate.

Instrumental conditions

(See Ultraviolet-Visible Spectroscopy 〈857〉.)

Mode: UV

Analytical wavelength: 233 nm

Cell: 1.0 cm

Blank: Medium

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of ezetimibe (C₂₄H₂₁F₂NO₃) dissolved:

Result = (A_U /A_S ) × C_S × V × (1/L) × 100

A _U= absorbance of the Sample solution

A_S = absorbance of the Standard solution

C_{​​​​​​​S} = concentration of USP Ezetimibe RS in the Standard solution (mg/mL)

V = volume of Medium, 500 mL

L = label claim (mg/Tablet)

Tolerances: NLT 80% (Q) of the labeled amount of ezetimibe (C₂₄H₂₁F₂NO₃) is dissolved.

Test 2: If the product complies with this test, the labeling indicates that it meets USP Dissolution Test 2.

Apparatus 2, Standard solution, Sample solution, Instrumental conditions, and Analysis: Proceed as directed in Test 1.

Buffer: 6.8 g/L of sodium acetate pH 4.5 prepared as follows. Dissolve 6.8 g of sodium acetate in 1 L of water. Add 3 mL of glacial acetic acid and mix. If necessary, adjust with 2 N acetic acid or 0.2 N sodium hydroxide to a pH of 4.5.

Medium: 0.45% (w/v) sodium dodecyl sulfate in Buffer; 500 mL

Time: 20 min

System suitability

Sample: Standard solution

Suitability requirements

Relative standard deviation: NMT 2.0% for 5 replicate readings

Tolerances: NLT 80% (Q) of the labeled amount of ezetimibe (C₂₄H₂₁F₂NO₃) is dissolved.

Uniformity of Dosage Units 〈905〉: Meet the requirements

5 IMPURITIES

5.1 Organic Impurities

Buffer, Mobile phase, Diluent, Sample solution, and Chromatographic system: Proceed as directed in the Assay.

System suitability solution: Weigh about 20 mg of USP Ezetimibe RS into a 100-mL volumetric flask. Dissolve in 10 mL of 0.01 N alcoholic sodium hydroxide. Place the capped volumetric flask into a 55° oven for 15 min. Remove from the oven and immediately add 2 mL of 0.1 N hydrochloric acid and about 50 mL of Diluent. Mix, allow to cool to room temperature, and dilute with Diluent to volume. Pass through a suitable filter of 0.45-μm pore size and discard the first 3 mL of the filtrate. [Note-Unidentified peak 2 with a relative retention time of about 1.14 is generated during hydrolysis.]

Sensitivity solution: 0.1 μg/mL of USP Ezetimibe RS in Diluent

5.2 System suitability

Samples: System suitability solution and Sensitivity solution

5.3 Suitability requirements

Resolution: NLT 1.5 between the ezetimibe peak and unidentified peak 2, System suitability solution

Signal-to-noise ratio: NLT 10, Sensitivity solution

5.4 Analysis

Sample: Sample solution

Calculate the percentage of each degradation product in the portion of Tablets taken:

Result = (r_U /r_T ) × 100

r_U = peak response of each impurity from the Sample solution

r_T = sum of all the peak responses from the Sample solution

Acceptance criteria: See Table 1.

Table 1

^a(3S,4S)-1-(4-Fluorophenyl)-3-[(S)-3-(4-fluorophenyl)-3-hydroxypropyl]-4-(4-hydroxyphenyl)azetidin-2-one and (3R,4R)-1-(4-Fluorophenyl)-3-[(R)-3-(4-fluorophenyl)-3-hydroxypropyl]-4-(4-hydroxyphenyl)azetidin-2-one.

^b Process-related impurity and controlled in the drug substance.

^c N,6-Bis(4-fluorophenyl)-2-(4-hydroxyphenyl)tetrahydro-2H-pyran-3-carboxamide.

^d(3R,4S)-1-(4-Fluorophenyl)-3-[3-(4-fluorophenyl)-3-oxopropyl]-4-(4-hydroxyphenyl)azetidin-2-one.

^e Total impurities include specified and unspecified degradation products. Process impurities are not included.

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Protect from moisture. Store at controlled room temperature.

Labeling: When more than one Dissolution test is given, the labeling states the Dissolution test used only if Test 1 is not used.

 USP Reference Standards 〈11〉

USP Ezetimibe RS