Rivaroxaban 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 

Rivaroxaban Tablets contain NLT 90.0% and NMT 110.0% of the labeled amount of rivaroxaban (C₁₉H₁₈ClN₃O₅S).

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

3 ASSAY 

Procedure 

Protect solutions containing rivaroxaban from light. Solution A: 0.01 M phosphoric acid 

Solution B: Acetonitrile 

Mobile phase: See Table 1. 

 Table 1 

Diluent: Solution A and Solution B (40:60) 

Standard solution: 0.2 mg/mL of USP Rivaroxaban RS in Diluent 

Sample solution: Nominally 0.2 mg/mL of rivaroxaban prepared as follows. Transfer Tablets (NLT 4) into an appropriate volumetric ask. Add a suitable amount of Diluent and sonicate to disintegrate and dissolve. Dilute with Diluent to volume. Pass the solution through a suitable lter of 0.45-µm pore size. 

Chromatographic system 

(See Chromatography 〈621〉, System Suitability.) 

Mode: LC 

Detector: UV 250 nm. For Identification B, use a diode array detector in the range of 200–400 nm. 

Column: 4.0-mm × 5.5-cm; 3-µm packing L1 

Column temperature: 45° 

Flow rate: 1 mL/min 

Injection volume: 5 µL 

System suitability 

Sample: Standard solution 

Suitability requirements 

Tailing factor: NMT 1.5 

Relative standard deviation: NMT 1.5% 

Analysis 

Samples: Standard solution and Sample solution 

Calculate the percentage of the labeled amount of rivaroxaban (C₁₉H₁₈ClN₃O₅S) in the portion of Tablets taken: 

Result = (r_U/r_S) × (C_S/C_U) × 100 

r_U = peak response of rivaroxaban from the Sample solution 

r_S = peak response of rivaroxaban from the Standard solution 

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

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

Acceptance criteria: 90.0%–110.0% 

4 PERFORMANCE TESTS 

Dissolution 〈711〉 

Buffer: 0.022 M sodium acetate; adjusted with sodium hydroxide or glacial acetic acid to a pH of 4.5 Medium 

For 2.5-mg Tablets: Buffer; 900 mL 

For 10-mg Tablets: 0.2% sodium dodecyl sulfate in Buffer; 900 mL 

For 15-mg and 20-mg Tablets: 0.4% sodium dodecyl sulfate in Buffer; 900 mL 

Apparatus 2: 75 rpm 

Times: 15 min for 10-mg, 15-mg, and 20-mg Tablets; 20 min for 2.5-mg Tablets 

Mobile phase: Acetonitrile and water (40:60) 

Standard stock solution: 0.55 mg/mL of USP Rivaroxaban RS in acetonitrile 

Standard solution 

For 2.5-mg Tablets: 0.003 mg/mL of USP Rivaroxaban RS from the Standard stock solution in Medium For 10-mg Tablets: 0.01 mg/mL of USP Rivaroxaban RS from the Standard stock solution in Medium For 15-mg and 20-mg Tablets: 0.02 mg/mL of USP Rivaroxaban RS from the Standard stock solution in Medium 

Sample solution: Pass a portion of the solution under test through a suitable filter of 10-µm pore size. Chromatographic system 

(See Chromatography 〈621〉, System Suitability.) 

Mode: LC 

Detector: UV 250 nm 

Column: 4.0-mm × 6.0-cm; 3-µm packing L1 

Column temperature: 40° 

Flow rate: 1 mL/min 

Injection volume: 10 µL for 10-mg, 15-mg, and 20-mg Tablets; 20 µL for 2.5-mg Tablets 

Run time: NLT 3 times the retention time of rivaroxaban 

System suitability 

Sample: Standard solution 

Suitability requirements 

Relative standard deviation: NMT 1.5% 

Analysis 

Samples: Standard solution and Sample solution 

Calculate the percentage of the labeled amount of rivaroxaban (C₁₉H₁₈ClN₃O₅S) dissolved: 

Result = (r_U /r_S) × C_S × V × (1/L) × 100 

r_U = peak response of rivaroxaban from the Sample solution  

r_S = peak response of rivaroxaban from the Standard solution 

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

V = volume of Medium, 900 mL 

L = label claim (mg/Tablet) 

Tolerances: NLT 80% (Q) of the labeled amount of rivaroxaban (C₁₉H₁₈ClN₃O₅S) is dissolved. 

Uniformity of Dosage Units 〈905〉: Meet the requirements 

5 IMPURITIES 

Organic Impurities 

Protect solutions containing rivaroxaban from light. 

Mobile phase, Diluent, Standard solution, Sample solution, and Chromatographic system: Proceed as directed in the Assay. System suitability solution: 2 µg/mL each of USP Rivaroxaban RS and USP Rivaroxaban Related Compound H RS in Diluent Sensitivity solution: 0.2 µg/mL of USP Rivaroxaban RS from the Standard solution in Diluent 

System suitability 

Samples: Standard solution, System suitability solution, and Sensitivity solution 

[Note—See Table 2 for the relative retention times.] 

Suitability requirements 

Resolution: NLT 2.0 between rivaroxaban and rivaroxaban related compound H, System suitability solution 

Relative standard deviation: NMT 1.5%, Standard solution 

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

Analysis 

Samples: Standard solution and Sample solution 

Calculate the percentage of any unspecified degradation product in the portion of Tablets taken: 

Result = (r_U/r_S) × (C_S/C_U) × 100 

r_U = peak response of each unspecified degradation product from the Sample solution 

r_S = peak response of rivaroxaban from the Standard solution  

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

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

Acceptance criteria: See Table 2. The reporting threshold is 0.1%. 

Table 2 

^a This impurity is included for establishing the Resolution requirement in System suitability. 

6 ADDITIONAL REQUIREMENTS 

Packaging and Storage: Preserve in well-closed containers. Store at controlled room temperature. 

USP Reference Standards 〈11〉 

USP Rivaroxaban RS 

USP Rivaroxaban Related Compound H RS 

(S)-4,5-Dichloro-N-({2-oxo-3-[4-(3-oxomorpholino)phenyl]oxazolidin-5-yl}methyl)thiophene-2-carboxamide. 

C₁₉H₁₇Cl2N₃O₅S470.32