Capecitabine Tablets
DEFINITION
Capecitabine Tablets contain NLT 93.0% and NMT 105.0% of the labeled amount of capecitabine (C15H22FN3O6).
IDENTIFICATION
• A. Infrared Absorption 
197K
197K
Analytical wave number:
1500–1760 cm
1
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.
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.
| Time (min) |
Solution B (%) |
Solution C (%) |
|---|---|---|
| 0 | 100 | 0 |
| 5 | 100 | 0 |
| 20 | 49 | 51 |
| 30 | 49 | 51 |
| 31 | 100 | 0 |
| 40 | 100 | 0 |
[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
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 = (rU/rS) × (CS/CU) × 100
| rU | = | = peak response from the Sample solution |
| rS | = | = peak response from the Standard solution |
| CS | = | = concentration of USP Capecitabine RS in the Standard solution (mg/mL) |
| CU | = | = nominal concentration of capecitabine in the Sample solution (mg/mL) |
Acceptance criteria:
93.0%–105.0%
PERFORMANCE TESTS
• Dissolution 711
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 fiberglass 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 = (AU/AS) × CS × (V/L) × 100
| AU | = | = absorbance of the Sample solution |
| AS | = | = absorbance of the Standard solution |
| CS | = | = 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
905:
Meet the requirements
IMPURITIES
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 = (rU/rS) × (CS/CU) × 100/F
| rU | = | = peak response for each impurity from the Sample solution |
| rS | = | = peak response for capecitabine from the Standard solution |
| CS | = | = concentration of USP Capecitabine RS in the Standard solution (mg/mL) |
| CU | = | = nominal concentration of capecitabine in the Sample solution (mg/mL) |
| F | = | = relative response factor for each impurity, from Impurity Table 1 |
Acceptance criteria
Individual impurities:
See Impurity Table 1.
Total degradation products:
NMT 2.0%
Impurity Table 1
| Name | Relative Retention Time |
Relative Response Factor |
Acceptance Criteria, NMT (%) |
|---|---|---|---|
| Capecitabine related compound A | 0.18 | 1.05 | 1.0 |
| Capecitabine related compound B | 0.19 | 0.81 | 1.0 |
| 2¢,3¢-Di-O-acetyl-5¢-deoxy-5-fluorocytidine* | 0.36 | 0.89 | — |
| 5¢-Deoxy-5-fluoro-N4-(2-methyl-1-butyloxycarbonyl)cytidine + 5¢-Deoxy-5-fluoro-N4-(3-methyl-1-butyloxycarbonyl)cytidine* | 0.95 | 1.01 | — |
| Capecitabine | 1.00 | 1.00 | — |
[1-[5-Deoxy-3-O-(5-deoxy- -d-ribofuranosyl)--d-ribofuranosyl]-5-fluoro-2-oxo-1,2-dihydropyrimidin-4-yl]-carbamic acid pentyl ester* |
1.06 | 1.00 | — |
| [1-[5-Deoxy-2-O-(5-deoxy--d-ribofuranosyl)--d-ribofuranosyl]-5-fluoro-2-oxo-1,2-dihydropyrimidin-4-yl]-carbamic acid pentyl ester* |
1.09 | 1.00 | — |
| Capecitabine related compound C | 1.11 | 0.91 | 0.5 |
[1-[5-Deoxy-3-O-(5-deoxy- -d-ribofuranosyl)--d-ribofuranosyl]-5-fluoro-2-oxo-1,2-dihydropyrimidin-4-yl]-carbamic acid pentyl ester* |
1.20 | 1.00 | — |
| 2¢,3¢-Di-O-acetyl-5¢-deoxy-5-fluoro-N4-(pentyloxycarbonyl)cytidine* | 1.37 | 0.85 | — |
| Individual unspecified degradation product | — | 1.00 | 0.1 |
| The impurities marked with an “*” are process impurities and are not included in the total degradation products. | |||
ADDITIONAL REQUIREMENTS
• Packaging and Storage:
Preserve in tight containers. Store at controlled room temperature.
• USP Reference Standards 11
11
USP Capecitabine RS 
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USP Capecitabine Related Compound A RS
5¢-Deoxy-5-fluorocytidine.
C9H12FN3O4 245.21
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5¢-Deoxy-5-fluorocytidine.
C9H12FN3O4 245.21
USP Capecitabine Related Compound B RS
5¢-Deoxy-5-fluorouridine.
C9H11FN2O5 246.19
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5¢-Deoxy-5-fluorouridine.
C9H11FN2O5 246.19
USP Capecitabine Related Compound C RS
2¢,3¢-O-Carbonyl-5¢-deoxy-5-fluoro-N4-(pentyloxycarbonyl)cytidine.
C16H20FN3O7 385.34
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2¢,3¢-O-Carbonyl-5¢-deoxy-5-fluoro-N4-(pentyloxycarbonyl)cytidine.
C16H20FN3O7 385.34
Auxiliary Information—
Please check for your question in the FAQs before contacting USP.
| Topic/Question | Contact | Expert Committee |
|---|---|---|
| Monograph | Feiwen Mao, M.S.
Senior Scientific Liaison 1-301-816-8320 |
(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 1-301-816-8129 rstech@usp.org |
USP35–NF30 Page 2471
Pharmacopeial Forum: Volume No. 35(5) Page 1113