Capecitabine 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

Capecitabine Tablets contain NLT 93.0% and NMT 105.0% of the labeled amount of capecitabine (C₁₅H₂₂FN₃O₆).

2 IDENTIFICATION

Change to read:

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

Analytical wave number: 1500–1760 cm−1

Sample: Grind 1 Tablet to a fine powder with a mortar and pestle. Mix 1 mg of this sample with 300 mg of potassium bromide.

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

Procedure

Diluent: Methanol, acetonitrile, and water (7:1:12)

Solution A: 0.1% mixture of glacial acetic acid in water

Solution B: Methanol, acetonitrile, and Solution A (7:1:12)

Solution C: Methanol, acetonitrile, and Solution A (16:1:3)

Mobile phase: See the gradient table below.

[Note—The following solutions may be sonicated as necessary.]

System suitability solution: Includes 0.6 μg/mL of USP Capecitabine RS, 0.6 μg/mL of USP Capecitabine Related Compound A RS, 0.6 μg/mL of USP Capecitabine Related Compound B RS, and 0.6 μg/mL of USP Capecitabine Related Compound C RS in Diluent

Standard solution: 0.6 mg/mL of USP Capecitabine RS in Diluent

Sample solution: Equivalent to 0.6 mg/mL of capecitabine, from powdered Tablets (NLT 20), in Diluent.[Note—Pass through a PVDF

membrane filter of 0.45-μm pore size, and use the filtrate.]

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 250 nm

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

Column temperature: 40°

Autosampler temperature: 5°

Flow rate: 1 mL/min

Injection size: 10 μL

System suitability

Samples: System suitability solution and Standard solution

[Note—For the purpose of peak identification, the approximate relative retention times are given in Impurity Table 1. The relative retention times are measured with respect to capecitabine.]

Suitability requirements

Resolution: NLT 1.0 between capecitabine related compound A and capecitabine related compound B, System suitability solution

Tailing factor: NMT 1.5, Standard solution

Relative standard deviation: NMT 2.0%, Standard solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of C₁₅H₂₂FN₃O₆ in the portion of Tablets taken:

Result = (r_U/r_S) x (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 Capecitabine RS in the Standard solution (mg/mL)

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

Acceptance criteria: 93.0%–105.0%

PERFORMANCE TESTS

Dissolution 〈711〉

Medium: Water; 900 mL, degassed

Apparatus 2: 50 rpm

Time: 30 min

Standard solutions

For Tablets labeled to contain 150 mg: 17 mg of USP Capecitabine RS in 100 mL of Medium

For Tablets labeled to contain 500 mg: 28 mg of USP Capecitabine RS in 50 mL of Medium

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

Analysis: Determine the amount of C₁₅H₂₂FN₃O₆ dissolved by selecting a wavelength with appropriate sensitivity between 300 and 330 nm on

portions of the Sample solution, suitably diluted with Medium, if necessary, in comparison with the appropriate Standard solution, using a 1-

mm quartz cell. Calculate the percentage of C₁₅H₂₂FN₃O₆ dissolved in each Tablet:

Result = (A_U/A_s ) × C_s × (V/L) × 100

A_U = absorbance of the Sample solution

A_s = absorbance of the Standard solution

C_s = concentration of capecitabine in the Standard solution (mg/mL)

V = volume of medium, 900 mL

L = Tablet label claim (mg)

Tolerances: NLT 80% (Q) of the labeled amount of C₁₅H₂₂FN₃O₆ is dissolved.

Uniformity of Dosage Units 〈905〉: Meet the requirements

4 IMPURITIES

4.1 Organic Impurities

Procedure

Diluent, Solution A, Solution B, Solution C, Mobile phase, System suitability solution, Standard solution, Sample solution, and Chromatographic system: Proceed as directed in the Assay.

Analysis

Samples: Standard solution and Sample solution

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

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

r_U = peak response for each impurity from the Sample solution

r_S = peak response for capecitabine from the Standard solution

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

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

F = relative response factor for each impurity, from Impurity Table 1

Impurity Table 1

The impurities marked with an “*” are process impurities and are not included in the total degradation products.

4.2 Acceptance criteria

Individual impurities: See Impurity Table 1.

Total degradation products: NMT 2.0%

5 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in tight containers. Store at controlled room temperature.

USP Reference Standards 〈11〉

USP Capecitabine RS

ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in tight containers. Store at controlled room temperature.

USP Reference Standards 〈11〉

USP Capecitabine RS

USP Capecitabine Related Compound A RS

5′-Deoxy-5-fluorocytidine.

C₉H₁₂FN₃O₄ 245.21

USP Capecitabine Related Compound B RS

5′-Deoxy-5-fluorouridine.

C₉H₁₁FN2O₅ 246.19

USP Capecitabine Related Compound C RS

2′,3′-O-Carbonyl-5′-deoxy-5-fluoro-N 4-(pentyloxycarbonyl)cytidine.

C₁₆H₂₀FN₃O₇ 385.34