Dismiss
InnovationQ will be updated on Sunday, Oct. 22, from 10am ET - noon. You may experience brief service interruptions during that time.
Browse Prior Art Database

5-[[4-[(2,3-Dimethyl-2H-indazol-6-yl)(methyl)amino] pyrimidin-2-yl]amino]-2-methylbenzenesulfonamide monohydrochloride

IP.com Disclosure Number: IPCOM000202288D
Publication Date: 2010-Dec-13
Document File: 8 page(s) / 346K

Publishing Venue

The IP.com Prior Art Database

This text was extracted from a PDF file.
This is the abbreviated version, containing approximately 56% of the total text.

Page 01 of 8

5-[[4-[(2,3-Dimethyl-2H-indazol-6-yl)(methyl)amino] pyrimidin-2-yl]amino]-2- methylbenzenesulfonamide monohydrochloride

    5-[[4-[(2,3-Dimethyl-2H-indazol-6-yl)(methyl)amino] pyrimidin-2-yl]amino]-2- methylbenzenesulfonamide monohydrochloride ("PZP") of the following formula:

N

H2N .HCl

S

   O O

is marketed under the trade name Votrient® by GlaxoSmithKline, indicated for the treatment of patients with advanced renal cell carcinoma.

The purity and the crystalline form of commercial PZP are reported herein.

Chromatographic purity of Votrient tablet

   One tablet of Votrient (200 mg) was dissolved in diluent with sonication to the concentration equivalent to 0.5mg/mL of API, filtered by PTFE filter and injected into UPLC system.

The UPLC conditions were:
Column & Packing: ACQUITY UPLC BEH C18, 1.7μm,100x2.1mm, PN

                186002352
Buffer 0.01M NH4HCO3 pH=7.8 spontaneous, filter on 0.2μm filter Eluent A; 90% :10% Buffer : Acetonitrile
Eluent B: Acetonitrile

Time % Eluent A % Eluent B

0 90 10
1.9 80 20
7.2 80 20
11.8 70 30

                    15 70 30 Equilibrium time: 1 min

N

N

N N NH

Gradient


Page 02 of 8

Sample volume: 2 μL
Flow Rate: 0.5 mL/min Detector: 254 nm Column temperature: 45 °C Autosampler
temperature

25°C

Diluent Methanol

The obtained results are described in the table below:

Purity Impurity Profile, RRT, % on area

Sample

                PZP RRT 0.13 RRT 0.28 Total Votrient sample 1 99.99 LT 0.01 LT 0.01 0.01 Votrient sample 2 99.99 LT 0.01 LT 0.01 0.01

QL of the method is 0.03% and DL is 0.01% for specified and any unspecified impurities.


Page 03 of 8

Impurity Profile Chromatogram of Votrient 200 mg Tablet

AU

0.010

PZP - 7.357

0.980

2.049

0.008

0.006

0.004

0.002

0.000

-0.002

0.00 2.00 4.00 6.00 8.00 10.00 12.00 14.00 16.00

Minutes

(This page contains 00 pictures or other non-text object)

Peak Name

RT

(min)

Area

(µV*sec)

% Area

Height

(µV)

1

2

3

4

5

0.90
0.98
2.05
5.60
7.36

A

MBS

CPMI PZP

552

646

8728918

0.0063
0.0074

99.9863

250 189

1375928

Determination of CPMI in Votrient tablet

    CPMI (N-(2-Chloropyrimidin-4-yl)-N-methyl-2,3-dimethyl-2Hindazol- 6-amine) is a direct raw material of PZP*HCl.

   One tablet of Votrient (200 mg) was dissolved in diluent with sonication to the concentration equivalent to 4.0mg/mL of API, filtered by PTFE filter and injected into UPLC system.

The UPLC conditions were:
Column & Packing: Acquity UPLC BEH C18 ,2.1x100mm, 1.7μm PN:186002352 Buffer 0.01M NH4HCO3 pH=7.8 spontaneous, filter on 0.2...