Impurity Identification, Isolation, and Characterization

SR.

NO.

PRODUCT

STANDARDS

CHEMICAL NAME

Qualified

1

ALLOPURINOL

Allopurinol

1,5-Dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one

EP & USP

Impurity-A

5-amino-1H-pyrazole-4-carboxamide

EP & USP

Impurity-B

5-(formylamino)-1H-pyrazole-4-carboxamide

EP & USP

Impurity-C

5-(4H-1,2,4-triazol-4-yl)-1H-pyrazole-4-carboxamide

EP & USP

Impurity-D

ethyl 5-amino-1H-pyrazole-4-carboxylate

USP

Impurity-E

ethyl 5-(formylamino)-1H-pyrazole-4-carboxylate

USP

2

BRINZOLAMIDE

Brinzolamide

(R)-4-(Ethylamino)-3,4-dihydro-2-(3-methoxypropyl)-2H-thieno [3,2-e]-1,2-thiazine-6-sulfonamide 1,1-dioxide

USP

Impurity-C

(2RS)-1-[benzyl[2-(2-methoxyphenoxy)ethyl]amino]-3-(9H-carbazole-4-yloxy)propan-2-ol

In-house

Impurity-D

(S)-3,4-Dihydro-4-hydroxy-2-(3-methoxypropyl)-4H-thieno-[3,2-e]-1,2-thiazine-6-Sulfonamide-1,1- dioxide

In-house

BZM 3

3-Bromoacetyl-5-chloro-2-thiophenesulfonamide

In-house

BZM4 Racemic

(4S)-6-chloro-3,4-dihydro-2H-thieno[3,2-e][1,2] thiazin-4-ol 1,1-dioxide Racemic standard

In-house

BZM6 Racemic

4(R)(S)-4-hydroxy-2-(3-methoxypropyl)-3,4-dihydro-2H-theino[3,2-e][1,2][thiazine-6-sulfonamide 1,1-dioxide Racemic standard

In-house

BZM Racemic

(S)(R)-(-)-4-Ethylamino-2,3-dihydro-2-(3-methoxypropyl)-4H-thieno-[3,2-e]-thiazine-6-sulphonamide-1,1-dioxide

In-house

3

DORZOLAMIDE HYDROCHLORIDE

Dorzolamide HCl

(4S,6S)-4-(Ethylamino)-5,6-dihydro-6-methyl-4H-thieno[2,3-b] thiopyran-2-sulfonamide 7,7-dioxide, monohydrochloride

EP&USP

Impurity-A

(4R,6R)-4-(ethyl amino)-6-methyl-5,6-dihydro-4H-thieno[2,3-

b]thiopyran-2-sulfonamide 7,7-dioxide

USP& In-house

Impurity-B

(4R,6S)-4-(ethyl amino)-6-methyl-5,6-dihydro-4H-thieno[2,3-

b]thiopyran-2-sulfonamide 7,7-dioxide

USP& In-house

4

BRIMONIDINE TARTRATE

Brimonidine Tartrate

5-Bromo-N-(4,5-dihydro-1H-imidazol-2-yl)- 6-quinoxalin-6- amine tartrate

USP/EP

Impurity-A

5-bromoquinoxalin-6-amine

In-house

Impurity-B

N-[(2E)-1-acetylimidazolidin-2-ylidene]-5-bromoquinoxalin-6-amine

In-house

Impurity-C

N-(4,5-dihydro-1H-imidazol-2-yl) quinoxalin-6-amine

In-house

Impurity-H

5-Chloro-N-(imidazolidin-2-ylidene) quinoxalin-6-amine tartrate

In-house

Impurity-E

2-(5-bromoquinoxalin-6-yl)guanidine

EP/USP

Impurity-D

2-[(5-bromoquinoxalin-6-yl)amino]imidazolidin-2-ol

In-house

5

RASAGILINE MESYLATE

Rasagiline Racemic

(1R,S)-N-Prop-2-yn-1-ylindan-1-amine methanesulfonic acid salt

In-house

Chloro impurity

Rasagiline Trans Chloro impurity

In-house

6

QUETIAPINE FUMARATE

Quetiapine Fumarate

2-[2-(4-Dibenzo[b,f][1,4]thiazepin-11-yl-1-piperazinyl) ethoxy] ethanol hemifumarate

USP/EP

Impurity-C

Dibenzo[b,f][1,4]thiazepine-11(10H)one

In-house

Impurity-B

11-(piperazin-1-yl) dibenzo [b, f] [1, 4] thiazepine dihydrochloride

USP & EP

Des Ethoxy Impurity

2-[2-(4-Dibenzo[b,f][1,4]thiazepine 11-yl-piperazinyl)] ethanol hydrochloride

USP

7

FEBUXOSTAT

Febuxostat

2-(3-cyano-4-isobutoxyphenyl)-4-methyl-1,3-thiazole- 5-carboxylic acid

NON-PHARMACOPI A

Impurity-A

Ethyl 2-(3-cyano-4-isobutoxyphenyl)-4-methylthiazole-5-carboxylate

In-house

Impurity-B

Ethyl 2-(3-carbamoyl-4-isobutoxyphenyl)-4-methylthiazole-5-carboxylate

In-house

8

DICYCLOMINE HYDROCHLORIDE

Dicyclomine HCl

[Bicyclohexyl]-1-carboxylic acid, 2-(diethylamino)ethyl ester, hydrochloride

EP &USP

Impurity A

Bicyclohexyl-1-carboxylic acid

EP &USP

Impurity B

2-(diethylamino)ethyl-1,1’-bi(cyclohexane)-1’-ene-12-carboxylate

In-house

9

BESIFLOXACIN HYDROCHLORIDE

Impurity A

R-Isomer

In-house

Impurity E

7-[(3R)-azepan-3-ylamino]-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydroquinoline-3-carboxylic acid.

In-house

Impurity F

7-[(3R)-azepan-3-ylamino]-8-chloro-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydroquinoline-3-carboxylic acid.

In-house

Impurity D

Besifloxacin dimer Impurity

In-house

Impurity G

(R)-3-Amino Hexahydro-1H-Azepan

In-house

BFX Racemic

7-[(3RS)-aminoazepan-1-yl]-8-chloro-1-cyclopropyl-6-fluoro-4-oxoquinoline-3-carboxylic acid hydrochloride.

In-house

10

LACOSAMIDE

S-isomer

2S-(acetylamino)-3-methoxy-N-(phenylmethyl)-propanamide

In-house / EP(A)

Impurity A

(2R)-2-amino-N-benzyl-3-methoxypropanamide

In-house (Imp D EP)

BBC1 R isomer

(2R)-N-benzyl-2-bromo-3-hydroxy propanamide

In-house

BBC S isomer

Tert-butyl [(1S)-2-(benzylamino)-1-(hydroxymethyl-2-oxoethyl] carbamate

In-house

Lacosamide Impurity B/ (O-Acetyl impurity)

(2R)-2-(acetylamino)-3-(benzylamino)-3-oxopropyl acetate

In-house EP

Lacosamide Impurity F

(2R)-2-(acetylamino)-N-benzyl-3-hydroxypropanamide

In-house EP

Lacosamide Impurity G

N-benzylacetamide

In-house EP

Lacosamide Impurity H

(2E)-2-acetamido-N-((2E)-1-(benzylamino)-3-methoxy-1-oxopropan-2-yl)-3-methoxypropanamide

In-house EP

Lacosamide Impurity I

(2E)-N-benzyl-2-[benzylcarbamoyl)amino]-3-methoxypropanamide

In-house EP

Lacosamide Impurity E (BBC2)

(2R)-2-amino-N-benzyl-3-hydroxypropanamide

In-house EP

11

APIXABAN

Methyl Ester Imp (Impurity B)

Methyl-1-(4-methoxy phenyl)-7-oxo-6-(4-(2-oxopiperidine-1-yl)phenyl)-4,5,6,7,-tetrahydro-1H-pyrazolo(3,4,-C)pyridine-3-carboxylate

In-house

Apixaban

1-(4-methoxyphenyl)-7-oxo-6-[4-(2-oxopiperidin-1-yl)phenyl]-4,5-dihydropyrazolo[3,4-c]pyridine-3-carboxamide

In-house

(APX 3)

Impurity A

1-(4-methoxyphenyl)-7-oxo-6-(4-(2-oxopiperidine-1-yl) phenyl)-4,5,6,7-tetrahydro-1H-pyrazolo [3,4-c]pyridine-3-carboxylic acid

In-house

12

CANAGLIFLOZIN

Canagliflozin

(2S,3R,4R,5S,6R)-2-[3-[[5-(4-fluorophenyl)thiophen-2-yl]methyl]-4-methylphenyl]-6-(hydroxymethyl)oxane-3,4,5-triol

In-house

Impurity A (Diastereomer)

(2R, 3R, 4R, 5S, 6R)-2-(3-((5-(4-fluorophenyl) thiophene-2-yl) methyl)-4-methylphenyl)-6-(hydroxymethyl) tetrahydro-2H-pyran-3, 4, 5-triol (CGF Diastereomer)

In-house

CGF

Hydroperoxide Impurity

(2S,3R,4R,5S,6R)-2-(3-((5-(4-fluorophenyl)thiophen-2-yl)(hydroperoxy)methyl)-4-methylphenyl)-6-(hydroxymethyl) tetrahydro-2H-pyran-3,4,5-triol

In-house

13

ALOGLIPTIN BENZOATE

Alogliptin benzoate

2-[[6-[(3R)-3-aminopiperidin-1-yl]-3-methyl-2,4-dioxopyrimidin-1-yl]methyl]benzonitrile;benzoic acid

In-house

Impurity A

(R)-2-((3-methyl-2,4-dioxo-6-(piperidin-3-ylamino)-3,4-dihydropyrimidin-1(2H)-yl)methyl)benzonitrile

In-house

Impurity B

2-(bromomethyl)benzonitrile

In-house

Impurity C

(R)-2-((1-(3-(2-cyanobenzyl)-1-methyl-2,6-dioxo-1,2,3,6-tetrahydropyrimidin-4-yl)piperidine-3-ylamino)methyl)benzonitrile

In-house

Impurity D

(R)-2-((6-(1-(3-(2-cyanobenzyl)-1-methyl-2,6-dioxo-1,2,3,6-tetrahydropyrimidin-4-yl)piperidin-3-ylamino)-3-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)methyl)benzonitrile

In-house

Impurity E

(R)-N-(1-(3-(2-cyanobenzyl)-1-methyl-2,6-dioxo-1,2,3,6-tetrahydropyrimidin-4-yl) piperidin-3-yl) benzamide

In-house

Impurity F

(R)-3-((6-(3-aminopiperidin-1-yl)-3,4-dihydro-3-methyl-2,4-

dioxopyrimidin-1(2H)-yl)methyl)benzonitrile hydrochloride

In-house

Impurity G

(R)-4-((6-(3-aminopiperidin-1-yl)-3,4-dihydro-3-methyl-2,4-

dioxopyrimidin-1(2H)-yl)methyl)benzonitrile hydrochloride

In-house

S-isomer

(S)-2-((6-(3-aminopiperidin-1-yl)-3-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)methyl) benzonitrile benzoate.

In-house

AGP Racemic

2-(6-(3-aminopiperidine-1-yl)-3-methyl-2-4-dioxo-3,4-dihydropyridin-1-(2H)-yl)methyl benzonitrile benzoate

In-house

14

MIRABEGRON

Mirabegron

2-(2-amino-1,3-thiazol-4-yl)-N-[4-[2-[[(2R)-2-hydroxy-2-phenylethyl]amino]ethyl]phenyl]acetamide

In-house

Dehydroxy Impurity(Imp A)

2-(2-aminothiazol-4-yl)-N-(4-(2-(phenethylamino)ethyl)phenyl)acetamide

In-house

Imp D

(R)N-(4-(2-aminothiazol-4-yl) acetamido)phenethyl-(2-hydroxy-2-phenylethyl acetamide

In-house

15

NEOSTIGMINE METHYL SULPHATE

Neostigmine

Neostigmine Methyl Sulphate

In-house

Impurity A

3-Hydroxy-N,N,N-trimethylanilinium methyl sulfate 3-hydroxy-N,N,N-trimethylanilinium

In-house

Impurity B

3-(dimethylamino) phenol

In-house

Impurity C

3-(dimethylamino) phenyl dimethylcarbamate

In-house

16

METOPROLOL SUCCINATE

MTS1

2-((4-(2-methoxyethyl)phenoxy)methyl)oxirane

In-house

Metoprolol Succinate

±1-(isopropyl amino)-3-(4-(2-methoxyethyl) phenoxy) propan-2-ol Succinate

In-house

MTS impurity A

(±)1-(ethylamino)-3-[4-(2-methoxyethyl)phenoxy]-propan-2-ol

USP

MTS impurity B (MTS1A)

(±)1-Chloro-2-hydroxy-3-[4-(2-methoxyethyl)phenoxy]-propane

USP

MTS impurity C

(±)4-[2-Hydroxy-3-(1-methylethyl) aminopropoxy] benzaldehyde

USP

MTS impurity D

(±)N,N-bis-[2-hydroxy-3-[4-(2-methoxyethyl)phenoxy] propyl](1-methylethyl)amine

USP

MTS impurity D Diol Impurity

3-(4,2 Methoxy ethyl )phenoxy propane 1,2 Diaol

EP

MTS Bis Ether Impurity

1,3-bis(4-(2-methoxyethyl)phenoxy)propan-2-ol

In-house

17

BREXPIPRAZOLE

Brexpiprazole

7-(4-(4-(benzo[b]thiophen-4-yl) piperazin-1-yl)butoxy)quinolin-2(1H)-on

In-house

Dimer Impurity

7,7-(butane-l,4-diylbis(oxy»bis(quinolin-2(1H)one

In-house

Bromo impurity BRX4

2-Bromo-7-(4-chloro butoxy)quinoline

In-house

Impurity D

1-(benzo[b]thiophen-4-yl)-4-(4-((2-oxo-1,2-dihydroquinolin-7-yl)oxy)butyl)piperazine-1,4-dioxide

In-house

19

AMIODARONE HCL

Amiodarone HCl

Amiodarone Hydrochloride

USP

Impurity H

2-chloro-N,N-diethylethanamine

USP

Impurity E

(2-butylbenzofuran-3-yl)(4-hydroxyphenyl)methanone

USP

Impurity F

(2-butylbenzofuran-3-yl)(4-hydroxy-3-odophenyl)methanone

In-house

20

ARIPIPRAZOLE

Aripiprazole

7-[4-[4-(2,3-dichlorophenyl)piperazin-1-yl]butoxy]-3,4-dihydro-1H-quinolin-2-one

USP

Impurity F

(4-(2,3-dichlorophenyl)-1- [4-(2-oxo-1,2,3,4tetrahydroquinolin-7-yloxy)butyl]piperazin 1-xide)

USP

Impurity G

(7-{4-[4-(2,3-dichlorophenyl)piperazin-1-yl]butoxy}quinolin-2(1H)-one)

USP

21

DOMPERIDONE

Domperidone

5-chloro-1-[1-[3-(2-oxo-2,3-dihydro-1H-benzimidazol-1-yl) propyl]piperidin-4-yl]-1,3-dihydro-2H-benzimidazol-2-one

EP

Domperidone Maleate

5-chloro-1-[1-[3-(2,3-dihydro-2-oxo-1H-benzimidazol-1-yl)propyl]-4-piperidinyl]-1,3-dihydro-2H-benzimidazol]-2-one maleate

IP/ EP

Impurity A

5-Chloro-1-(piperidin-4-yl)-1,3-dihydro-2H-benzimidazol-2-one

EP

Impurity B

4-(5-chloro-2-oxo-2,3-dihydro-1H-benzimidazol-1-yl)-formylpiperidine

EP

Impurity C

cis-4-(5-chloro-2-oxo-2,3-dihydro-1H-benzimidazol-1-yl)-1-[3-(2-oxo-2,3-dihydro-1H-benzimidzol-1yl)propyl]piperidine-1-oxide

EP

Impurity F

1-3-bis[3-[4-(5-chloro-2-oxo-2,3-dihydro-1H-benzimidazol-1-yl)piperidine-1-yl]propyl]-1,3dihydro-2H-benzimidazol-2-one

EP

22

NITRO IMPURITIES

BIM Nitroso Impurity

(4-Bromophenyl)(4-nitrosoindolin-7-yl)methanone

In-house

DNPI

N-Nitroso piperazine dimer (1,4-dinitroso piperazine)

In-house

NDBA

N-Nitrosodibutylamine

In-house

NDBzA

N-Nitroso dibenzyl amine

In-house

NDEA

N-Ethyl-N-nitrosoethanamine

In-house

NDIBA

N-Nitrosodibutylamine

In-house

NDMA

N-Nitrosodimethylamine

In-house

NDPA

N-Nitrosodipropyl amine

In-house

NEIPA

N-Nitrosoethylisoprpylamine

In-house

NELMA

N-Nitrosomethyl ethanolamine

In-house

NMBA

4-Methyl(nitroso)aminobutanoic acid

In-house

NMOR

N-Nitrosomorpholine

In-house

NPIP

N-Nitrosopiperidine

In-house

NMPHA

N-Methyl-N-nitrosoaniline

In-house

NPYR

N-Nitrosopyrrolidine

In-house

MNPI

N-Nitroso piperazine

In-house

varenicline nitroso impurity

VC09

8-Nitroso-7 ,8,9,10-tetrahydro-6H -6,10-methanoazepino [4,5-9]quinoxaline (VC09)

In-house

23

IRGANOX IMPURITIES

IRG1010

Irganox 1010

In-house

IRG1076

Irganox 1076

In-house

24

CETIRIZINE

Impurity A/ CBHP

1-[(4-Cbloropbenyl)pbenylmetbyl] piperazine

EP/ USP

Impurity B/ Cetirizine

AceticAcid

2-(4-[(4-cbloropbenyl)pbenylmetbyl] piperazin-l-yl)acetic acid

EP/ USP

Impurity C/2-chlorocetirizine

2-(2-{4-[(2-Chlorophenyl)phenylmethyl]piperazine-l-yl}ethoxy)acetic acid

EP/ USP

Impurity D (Dimer)

1,4-bis[(4-chlorophenyl)phenylmethyl]piperazine

EP/ USP

Impurity E

(RS)-2-[2-[2-[4-[(4-chlorophenyl)phenylmethyl] piperazin-l-yl]ethoxy] ethoxy]acetic acid

EP

Impuritv F / Deschloro

2-[2-(4-Diphenylmethyl)piperazine-l-yl]ethoxy acetic acid

EP/ USP

CBHP-Nitroso Impurity

1-((4-cbloropbenyl)(pbenyl)metbyl)-4-nitrosopiperazine

In-house

CPB

(Chloromethvlene ) dibenzene

In-house

25

RIVAROXABAN

Impurity B

(S)-N-((2-oxo-3-(4-(3-oxomorpholino)phenyl)oxolidin-5-yl)methyl acetamide (Imp-B)

EP/ USP

Impurity D

N,N-Bis[[(5S)-2-oxo-3-[4-(3-oxo-4-morpholinyl)phenyl]-5-oxazolidinyl]methyl]urea (Imp-D)

EP/ USP

Impurity E

N-[[(5S)-2-Oxo-3-[4-(3-oxomorpholin-4-yl)phenyl]-1,3-oxazolidin-5-yl]methyl]thiophene-2- carboxamide(Imp E)

EP/ USP

Impurity H

(S)-4,5-Dichloro-N-((2-oxo-3-(4-(3-oxomorpholino)phenyl)oxazolidin-5-yl)methyl)thiophene-2-carboxamide (Imp H)

EP/ USP

Impurity I

(S)-2-(2-(2-Chloro-N-(4-(5-((2-chlorothiophene-5-carboxamido)methyl)-2-oxooxazolidin-3-yl)phenyl)thiophene-5-carboxamido)ethoxy)acetic acid

EP/ USP

RVX Racemic

(RS)-5-Chloro-N-{[2-oxo-3[4-(3-oxomorpholin-4-yl phenyl]oxolidin-5-yl]methyl}thiophene-2-carboxamide ( RVX Racemic)

EP/ USP

26

DOXYLAMINE SUCCINATE

ImpurityA / (DPPA)

N,N-DIMETHYL-2-(1-PHENYL-1-(PYRIDIN-4-YL)ethoxy)ethan-1-

amine (DPPA)

In-house

Impurity B

1-phenyl-1-(pyridin-2-yl)ethan-1-ol . Hydrochloride

In-house

Impurity C

N,N-DIMETHYL-2-(PHENYL(PYRIDIN-2-YL)methoxy)ethan-1-

amine

In-house

Impurity D

phenyl(pyridin-2-yl)methanone

In-house

27

SITAGLIPTINE HCL

(BTBA Racemic)

(R,S)-3-((tert-butoxycarbonyl)amino)-4-(2,4,5-trifluorophenyl) butanoic acid

In-house

(SGP1-RAC)

tert-Butyl (4-oxo-4-(3-(trifluoromethyl)-5,6-dihydro-[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl)-1-(2,4,5-trifluorophenyl)butan-

2-yl)carbamate

In-house

(SGP1)

tert-Butyl-(R)-(4-oxo-4-(3-(trifluoromethyl)-5,6-dihydro-[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl)-1-(2,4,5-trifluorophenyl)butan-

2-yl)carbamate

In-house

(BTBA DIMER)

(R)-3-(R)-3-((tert butoxycarbonyl)amino)-4(2,4,5-triflurophenyl)butanoic acid

In-house

(De-Boc acid Impurity)

(R)-3-amino-4-(2,4,5-trifluorophenyl)butanoic acid

In-house