GGDAC – PHARMACOPEIAL METHOD EVALUATION

PRODUCT: Structure:

RIVAROXABAN

U.S. PHARMACOPEIA METHOD: Enantiomeric Purity:

[Reference: USP PF Online]

Chromatographic conditions:

Column : Chiralcel OD 250 mm * 2.0 mm, 10 μm (L40)

Mobile phase : n-Heptane: Ethanol (70:30; v/v)

Flow rate : 0.2 mL/min

Injection volume : 3.0 µL

Column temperature : 50°C

UV detection : 250 nm

Run time : NLT 1.5 times the retention time of Rivaroxaban

Note:

• Used Chiracel OD, 250 mm * 2.1 mm, 10 microns column)

• The column temperature as per the method is 10°C more that the recommended column maximum
temperature of 40°C.

Solution preparations:

Diluent: Acetonitrile: Ethanol (50:50; v/v)

System suitability solution:

System suitability solution containing 0.4 mg/mL of USP Rivaroxaban RS and 0.004 mg/mL of
USP Rivaroxaban R-Enantiomer was prepared by adding Acetonitrile up to 50% of volumetric
flask sonicated to dissolve and diluted with ethanol to the volume.

Sample solution:

Sample solution containing 0.4 mg/mL of Rivaroxaban was prepared by adding Acetonitrile up
to 50% of volumetric flask sonicated to dissolve and diluted with ethanol to the volume.

Note: Sonication of 10-15 minutes is required to dissolve the sample solution.

Page 1 of 4
 GGDAC – PHARMACOPEIAL METHOD EVALUATION
PRODUCT: Structure:

RIVAROXABAN

System suitability requirements:

Resolution:

NLT 1.5 between Rivaroxaban R-Enantiomer and Rivaroxaban.

Tailing factor:

NMT 1.5 for Rivaroxaban.

System suitability solution results:

Peak Retention Time Relative Resolution Tailing factor

(RT) Retention Time (Rs)
(RRT)

R-Enantiomer 23.32 min. 0.81 -- 1.11

Rivaroxaban 28.72 min 1.0 2.65 1.27

Note: Observed retention times different of 4.0 minutes and 6.0 minutes for R-enantiomer and
Rivaroxaban peaks respectively against the retention time mentioned in the monograph.

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 GGDAC – PHARMACOPEIAL METHOD EVALUATION
PRODUCT: Structure:

RIVAROXABAN

Typical Chromatograms:

Blank:
DAD1A, Sig=250,4Ref=off (E:\CHEMSTATION\1\DATA\10_19199_RIVAROXABAN_USP\10_11190005.D)
mAU

60

50

40

30

20

10

5 10 15 20 25 30 35 40 45 min

System Suitability solution:

DAD1A, Sig=250,4Ref=off (E:\CHEMSTATION\1\DATA\10_19199_RIVAROXABAN_USP\10_11190008.D)
28.720 - Rivaroxaban

mAU

40

30

20
23.319 - R-Enantiomer

10

5 10 15 20 25 30 35 40 45 min

Page 3 of 4
 GGDAC – PHARMACOPEIAL METHOD EVALUATION
PRODUCT: Structure:

RIVAROXABAN

Test solution:

DAD1 A, Sig=250,4 Ref=off (E:\CHEMSTATION\1\DATA\10_19199_RIVAROXABAN_USP\10_11190009.D)

28.710 - Rivaroxaban
mAU

40

30

20

10

5 10 15 20 25 30 35 40 45 min

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