1-s2.0-S0731708513003099-main (2).pdf

8/9/2019 1-s2.0-S0731708513003099-main (2).pdf

1/25

Journal of Pharmaceutical and Biomedical Analysis 86 (2013) 11–35

Contents lists available at ScienceDirect

Journal

of

Pharmaceutical

and

Biomedical

Analysis

j o u r n a l h o m e p a g e : w w w . e l s e v i e r . c o m / l o c a t e / j p b a

Review

Forced degradation and impurity profiling: Recent trends in analytical

perspectives

Deepti Jain a , Pawan Kumar Basniwal a , b , *

a School of Pharmaceutical Sciences, Rajiv Gandhi Technological University, Bhopal 462 033, Madhya Pradesh, India b LBS College of Pharmacy, Jaipur 302 004, Rajasthan, India

a

r

t

i

c

l

e

i

n

f

o

Article history:

Received 9 May 2013

Received

in

revised

form

28

June

2013

Accepted 7 July 2013

Available online 31 July 2013

Keywords:

Impurity

Forced degradation profiling

Analytical perspectives

active pharmaceutical ingredient

Drug products

a

b

s

t

r

a

c

t

This

review

describes

an

epigrammatic

impression

of

the

recent

trends

in

analytical

perspectives

of

degra-

dation

and

impurities

profiling

of

pharmaceuticals

including

active

pharmaceutical

ingredient

(API)

as

well

as

drug

products

during

2008–2012.

These

recent

trends

in

forced

degradation

and

impurity

profiling

were

discussed

on

the

head

of

year

of

publication;

columns,

matrix

(API

and

dosage

forms)

and

type

of

elution

in

chromatography

(isocratic

and

gradient);

therapeutic

categories

of

the

drug

which

were

used

for

anal-

ysis.

It

focuses

distinctly

on

comprehensive

update

of

various

analytical

methods

including

hyphenated

techniques

for

the

identification

and

quantification

of

thresholds

of

impurities

and

degradants

in

different

pharmaceutical

matrices.

c 2013

Elsevier

B.V.

All

rights

reserved.

Abbreviations:

13

C

NMR,

13

carbon

nuclear

magnetic

resonance

spectroscopy;

1D

/

2D NMR, one dimensional / two dimensional nuclear magnetic resonance; 1 H NMR,

proton nuclear magnetic resonance spectroscopy; AAMRT, auto-associative multi-

variate regression trees; ACN, acetonitrile; APCI-MS, atmospheric-pressure chemical-

ionization mass spectrometry; API, active pharmaceutical ingredient; BADGE, bisphe-

nol

A

diglycidyl

ether;

BEH,

bridged

ethylene

hybrid;

C 6 H 6 , benzene; CAD, charged

aerosol

detector;

CCD,

central

composite

design;

CCl 4 , tetrachloromethane; CEAD,

coulometric electrode array detection; CH 2

Cl 2

, methylene chloride; CH 3

COONH 4

, am-

monium acetate; CHCl 2

CH 2

Cl, 1,1,2-trichloro ethane; CHCl 3

, chloroform; CID, collision-

induced dissociation; CO 2

, carbon dioxide; COPD, chronic obstructive pulmonary

disease; DAD / MS, diode array detector-mass spectrometry; DEPT, distortionless en-

hancement by polarization transfer; EDTA, ethylene diamine tetra acetic acid; ELSD,

evaporative light scattering detector; EMEA, European agency for the evaluation of

medicinal products; ESI / MS n , electronspray ionization multi-stage or tandem mass

spectrometry; ESI-FTICR-MS, electrospray ionization Fourier transform ion cyclotron

resonance mass spectrometry; USFDA, US Food and Drug Administration; FTICR,

Fourier transform ion cyclotron resonance; FT-IR, Fourier transform infrared; GC-

FID,

gas

chromatography-flame

ionization

detector;

GC–MS,

gas

chromatography–mass

spectrometry;

GFC,

gel

filtration

chromatography;

GTIs,

genotoxic

impurities;

H 2

O, water; H 3

PO 4

, phosphoric acid; HCl, hydrochloric acid; HCOOH, formic acid;

HCOONH 4

, ammonium formate; HEIP, 1,1,1,3,3,3-hexafluoroisopropanol; HILIC, hy-

drophilic interaction chromatography; HPAE-IPAD, high-performance anion-exchange

chromatography-integrated pulsed amperometric detection; HPLC, high performance

liquid chromatography; HPLC / ESI-MS, high-performance liquid chromatography /

electrospray ionization mass spectrometry; HP-SEC, high-performance size-exclusion

chromatography; HPTLC, high performance thin layer chromatography; ICH, Interna-

tional Conference on Harmonization; IFM, impurity fate mapping; IND, investigational

new drugs; IPA, isoproyl alcohol; K 2 HPO 4 , dipotassium hydrogen phosphate; KH 2 PO 4 ,

potassium dihydrogen phosphate; KOH, potassium hydroxide; LC / MS / MS, liquid

chromatography–tandem

mass

spectrometry;

ESI-CID-MS

/

MS,

electrospray

ioniza-

tion,

collision-induced

dissociation

and

tandem

mass

spectrometry;

LC–ESI-MS

n ,

liq-

uid chromatography–electro spray ionization-tandem mass spectrometer; LC–ESI-QT /

1. Introduction

“A clean bill of health of public” is the ultimate motto of pharma-

ceutical industries.” The objective of the pharmaceutical industries is to protect the public health by enabling the patients to get proper

medicine in proper dose and efficacy at an affordable cost. Thus, safety

and efficacy of pharmaceuticals are two fundamental issues of im-

portance in drug therapy. The safety of a drug is determined by its

pharmacological–toxicological profile as well as the adverse effects

caused by the impurities in bulk and dosage forms, i.e., the safety of

MS / MS, liquid chromatography–tandem mass spectrometry using electrospray ion-

ization

source

and

Q-trap

mass

analyzer;

LC–MS,

liquid

chromatography–mass

spec-

trometry; LiCl, lithium chloride; MDMA, 3,4-methylenedioxy-N-methylamphetamine;

MECC, micellar electrokinetic capillary chromatography; MEKC, micellar electrokinetic

chromatography; MeOH, methanol; MPLC, medium pressure liquid chromatography;

MPTP, N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine; CE, capillary electrophoresis;

MS,

mass

spectrometry;

Na

2

HPO

4

,

disodium

phosphate;

Na

3

PO

4

,

sodium

phosphate;

NaCl, sodium chloride; NDA, New Drug Application; NH 3 , ammonia; NH 4 H 2 PO 4 , am-

monium dihydrogen phosphate; NH 4 OH, ammonium hydroxide; NOESY, nuclear over-

hauser effect spectroscopy; NSAIDs, non-steroidal anti-inflammatory drugs; OVIs, or-

ganic volatile impurities; PCA, principal component analysis; PDA, photodiode ar-

ray; PDA-MS, photodiode array detector-mass spectrometry; PFPA, pentafluoropro-

pionic acid anhydride; Q-TOF, quadrupole-time-of-flight; RI, refractive index; RRF, rel-

ative

response

factor;

SDS,

sodium

dodecyl

sulfate;

SDS-PAGE,

sodium

dodecyl

sulfate

polyacrylamide gel electrophoresis; SFC, supercritical fluid chromatography; SPME,

headspace solid phase microextraction; TEA, triethylamine; TFA, trifluoroacetic acid;

Tris, trisaminomethane; UPLC, ultra performance liquid chromatography.

* Corresponding author at: LBS College of Pharmacy, Jaipur 302 004, Rajasthan, India.

Tel.: + 91 9414788171.

E-mail addresses: [email protected] (D. Jain) [email protected]

(P.K. Basniwal).

0731-7085/ $ - see front matter c 2013 Elsevier B.V. All rights reserved.

http://dx.doi.org/10.1016/j.jpba.2013.07.013

http://dx.doi.org/10.1016/j.jpba.2013.07.013http://dx.doi.org/10.1016/j.jpba.2013.07.013http://dx.doi.org/10.1016/j.jpba.2013.07.013http://dx.doi.org/10.1016/j.jpba.2013.07.013http://dx.doi.org/10.1016/j.jpba.2013.07.013http://dx.doi.org/10.1016/j.jpba.2013.07.013http://dx.doi.org/10.1016/j.jpba.2013.07.013http://dx.doi.org/10.1016/j.jpba.2013.07.013http://dx.doi.org/10.1016/j.jpba.2013.07.013http://dx.doi.org/10.1016/j.jpba.2013.07.013http://dx.doi.org/10.1016/j.jpba.2013.07.013http://dx.doi.org/10.1016/j.jpba.2013.07.013http://dx.doi.org/10.1016/j.jpba.2013.07.013http://dx.doi.org/10.1016/j.jpba.2013.07.013http://dx.doi.org/10.1016/j.jpba.2013.07.013http://dx.doi.org/10.1016/j.jpba.2013.07.013http://dx.doi.org/10.1016/j.jpba.2013.07.013http://www.sciencedirect.com/science/journal/07317085http://www.sciencedirect.com/science/journal/07317085http://www.elsevier.com/locate/jpbahttp://www.elsevier.com/locate/jpbahttp://www.elsevier.com/locate/jpbahttp://www.elsevier.com/locate/jpbahttp://www.elsevier.com/locate/jpbahttp://www.elsevier.com/locate/jpbahttp://www.elsevier.com/locate/jpbahttp://www.elsevier.com/locate/jpbahttp://www.elsevier.com/locate/jpbahttp://www.elsevier.com/locate/jpbahttp://www.elsevier.com/locate/jpbahttp://www.elsevier.com/locate/jpbahttp://www.elsevier.com/locate/jpbahttp://www.elsevier.com/locate/jpbahttp://www.elsevier.com/locate/jpbahttp://www.elsevier.com/locate/jpbahttp://www.elsevier.com/locate/jpbahttp://www.elsevier.com/locate/jpbahttp://www.elsevier.com/locate/jpbahttp://www.elsevier.com/locate/jpbahttp://www.elsevier.com/locate/jpbahttp://www.elsevier.com/locate/jpbahttp://www.elsevier.com/locate/jpbahttp://www.elsevier.com/locate/jpbahttp://www.elsevier.com/locate/jpbahttp://www.elsevier.com/locate/jpbahttp://www.elsevier.com/locate/jpbahttp://www.elsevier.com/locate/jpbahttp://www.elsevier.com/locate/jpbahttp://www.elsevier.com/locate/jpbahttp://www.elsevier.com/locate/jpbahttp://www.elsevier.com/locate/jpbahttp://www.elsevier.com/locate/jpbahttp://www.elsevier.com/locate/jpbahttp://www.elsevier.com/locate/jpbahttp://www.elsevier.com/locate/jpbahttp://www.elsevier.com/locate/jpbahttp://www.elsevier.com/locate/jpbahttp://www.elsevier.com/locate/jpbahttp://www.elsevier.com/locate/jpbahttp://www.elsevier.com/locate/jpbahttp://www.elsevier.com/locate/jpbahttp://www.elsevier.com/locate/jpbahttp://www.elsevier.com/locate/jpbahttp://www.elsevier.com/locate/jpbahttp://www.elsevier.com/locate/jpbahttp://www.elsevier.com/locate/jpbahttp://www.elsevier.com/locate/jpbahttp://www.elsevier.com/locate/jpbahttp://www.elsevier.com/locate/jpbahttp://www.elsevier.com/locate/jpbahttp://www.elsevier.com/locate/jpbahttp://www.elsevier.com/locate/jpbahttp://www.elsevier.com/locate/jpbahttp://www.elsevier.com/locate/jpbahttp://www.elsevier.com/locate/jpbamailto:[email protected]:[email protected]:[email protected]:[email protected]://dx.doi.org/10.1016/j.jpba.2013.07.013http://dx.doi.org/10.1016/j.jpba.2013.07.013mailto:[email protected]:[email protected]://crossmark.dyndns.org/dialog/?doi=10.1016/j.jpba.2013.07.013&domain=pdfhttp://www.elsevier.com/locate/jpbahttp://www.sciencedirect.com/science/journal/07317085http://dx.doi.org/10.1016/j.jpba.2013.07.013

8/9/2019 1-s2.0-S0731708513003099-main (2).pdf

2/25

8/9/2019 1-s2.0-S0731708513003099-main (2).pdf

3/25

D. Jain, P.K. Basniwal / Journal of Pharmaceutical and Biomedical Analysis 86 (2013) 11–35 13

Table 1

Different terminology used for impurities [ 10 ].

Impurity Description

Starting material Materials that are used to begin the synthesis of an API

Intermediates Produced during synthesis of the desired material, especially when they have been isolated and

characterized

Penultimate intermediate Last compound in synthesis chain prior to production of final compound. Also known as final

Intermediate

By-products Unplanned compounds produced in the reaction

Transformation

products

Relatively

nondescript

term

that

relates

to

theorized

and

non-theorized

products

that

may

be

produced in the reaction, which can include synthetic derivatives of by-products

Interaction products It considers interactions that could occur between various involved chemicals intentionally or

unintentionally. Two types of interaction products that can be commonly encountered are drug

substance–excipient interactions and drug substance-container / closure interactions

Related products Similar chemical structures as the API and may exhibit potentially similar biological activity

Degradation products Produced because of decomposition of the material of interest or active ingredient

Foreign substances Introduced by contamination or adulteration, not as a consequence of synthesis or preparation, are

labeled foreign substances, e.g., pesticides in oral analgesics

Toxic impurities Have significant undesirable biological activity, even as minor components; and they require

individual identification and quantification by specific tests

Concomitant components Bulk pharmaceutical chemicals may contain concomitant components, e.g., antibiotics that are

mixtures

and

are

geometric

and

optical

isomers

Signal impurities Impurities include some process-related impurities or degradation products that provide key

information about process

Ordinary impurities Impurities in bulk pharmaceutical chemicals that are innocuous by virtue of having no significant

undesirable biological activity in amounts present are called ordinary impurities

Organic volatile impurities Residual solvents that may be found in drug substance. ICH classification: Class I ( to be avoided ): C 6 H 6 ,

CCl

4

,

1,2-dichloromethane,

1,1-dichloroethane,

and

1,1,1-trichloroethane.

Class

II

(

should

be

limited

):

ACN, CHCl 3 , CH 2 Cl 2 , pyridine CHCl 2 CH 2 Cl, and 1,4-dioxane. Class III: low toxic potential and permitted

daily exposure of 50 mg or more. Class IV : solvents for which adequate toxic data are not available

Organic impurities Starting materials, process-related impurities, intermediates, and degradation products

Inorganic impurities Salts, catalysts, ligands, heavy metals or other residual metals

Other materials Filter aids and charcoal

Residual

solvents

Organic

and

inorganic

liquids

used

during

production

and

/

or

crystallization

Chiral impurities Differ only in the arrangement of their atoms in three-dimensional space. The differences in

pharmacological / toxicological profiles have been observed with chiral impurities in vivo

Fig. 2. Chromatograms recorded from the mixture containing 1 µ g ml −1 of PIB and

its four impurities on coulometric electrodes at increasing potentials: 300, 400, 500,

600, 700, 800, 850, and 900 mV. (Reuse with the permission of Elsevier Limited, The

Boulevard, Langford Lane, Kidlington, Oxford, OX5 1GB, UK.)

[ 48 ]. HPLC method was transferred to develop ultra-performance

liquid chromatography (UPLC) equipped with BEH column for de-

termination of primaquine phosphate along with its related sub-

stance within run time of 5 min [ 50 ]. Two impurities of tazarotene

were characterized by means of NMR analysis as ethyl 6-((4,4-

dimethyl-4 H -thiochromen-6-yl)ethynyl)nicotinate and 1,4-bis(4,4-

dimethylthiochroman-6-yl)buta-1,3-diyne, which are by-product of

synthetic process [ 53 ].

2.1.1.2. Forced degradation profiling HPLC with fluorescence detec-

tor was employed to study stability of betahistine in different forced

degradation conditions (heat, moisture, acid–base, and ultra-violet

light), where two potential degradation products were identified. The

dansylated products of UV-degraded betahistine were well separated

by thin-layer chromatography [ 22 ]. Second order reaction was fol-

lowed by alkaline forced degradation of bicalutamide, where an acid

and an amine were identified as alkaline degradants [ 24 ]. Very in-

teresting,

four

major

degradation

products

of

dexamethasone

in

its

coated drug-eluting stents and drug-loading solution were identified

which was used for local drug delivery to prevent restenosis [ 30 ].

Both + ESI and −ESI modes of LC–MS were used to characterize three

known and two unknown forced degradation products of glimepiride

formed under different stress conditions. Degradants were formed

due to hydrolysis of sulfonylurea and lactam bridge [ 39 ] while l -

thyroxine was determined in presence of eight degradation impurities

and its dosage form excipients [ 40 ]. A degradation product of pridinol

mesylate was identified as the dehydrated and N-oxidation deriva-

tives, which was formed by first-order kinetics of the acid-catalyzed

degradation of pridinol [ 49 ].

2.1.1.3.

Impurity

and

forced

degradation

profiling Mixture of phos-

phate buffer and acetonitrile were used to separate three process-

related impurities and degradation products (different forced

degradation conditions) of almotriptan malate [ 18 ]. In addition

to four known impurities of carvedilol, one unknown degrada-

tion product was identified as N-[(2RS)-3-(9 H -carbazol-4-yloxy)-2-

hydroxypropyl]-N-[2-(2-methoxyphenoxy)ethyl]hydroxylamine in

tablet dosage form which was found as exceeded thresholds of

ICH Q3B guidelines [ 27 ]. Reversible acetylcholinesterase inhibitor,

donepezil hydrochloride was assayed along with four impurities and

an excipient in oral pharmaceutical formulation, where selectivity of

method was assured from forced degradation of the drug [ 32 ]. Degra-

dation pathway for forced degradation behavior of enalapril maleate

was identified in different stress conditions [ 34 ] and two degradation

impurities of epirubicin were found in aqueous formulation [ 35 ].

8/9/2019 1-s2.0-S0731708513003099-main (2).pdf

4/25

14 D. Jain, P.K. Basniwal / Journal of Pharmaceutical and Biomedical Analysis 86 (2013) 11–35

Table 2

Representative

chromatographic

analytical

methods

of

impurity

and

forced

degradation

profiling

during

2008–2012.

S.

no.

Name

of

drug

Matrix;

therapeutic

category

Impurity

/

degradant

Column

/

stationary

phase

Mobile

phase

Detection

Year

[Ref.]

1.

Methamphetamine

hydrochloride

API; psychostimulant 29 impurities Capillary column, 30 m

× 0.32

mm

× 1. 0

mm

Nitrogen gas Mass

selective

detector

2008 [ 17 ]

2.

Almotriptan

malate API;

antimigraine

3

impurity

C18,

250

mm

× 4.6

mm,

5 µ m Sodium

phosphate

buffer (pH 7.6):ACN

(80:20)

227

nm

2008

[

18

]

3. Alprazolam Tablets; anxiolytic 20 degradant C18, 150 mm × 4.6 mm,

5 µ m

ACN:CH 3 COOH (25

mM, pH 4.0);

gradient

234 nm 2008 [ 19 ]

4. Atomoxetine

hydrochloride

API; antidepressants Phenyl

methylamino-propanol

and mandelic acid

C8, 50 mm × 4.6 mm,

3.5 µ m

O -Phosphoric acid

(25 mM, pH 2.5)

and Octane sulfonic

acid (25

mM):n-Propanol

(73:27)

215 nm 2008 [ 20 ]

5. Atorvastatin

calcium

Tablets;

anti-hyperlipidemic

An acid degraded impurity C18 (BEH), 100 mm ×

2.1 mm, 1.7 µ m

ACN:CH 3

COONH 4

buffer (pH 4.7; 0.01

M), gradient

247 nm 2008 [ 21 ]

6. Betahistine API and tablet;

vasodilator

9 degradants C18, 250 mm × 4.6 mm,

5 µ m

ACN: sodium

acetate (0.02 mM,

pH 4.5); gradient

UV – 254 nm;

Fluorescence

336 and 531

nm

2008 [ 22 ]

7. Betamethasone

17-valerate

API; steroid 2 impurities C18, 250 mm × 4.6 mm,

5 µ m

ACN:H 2 O (60:40) PDA-MS

detector

2008 [ 23 ]

8. Bicalutamide API and tablet;

anticancer

2 degradants and 6

process-related

impurities

C18, 250 mm × 4.6 mm,

5

µ m

0.01 M KH 2 PO 4 (pH

3.0):ACN

(50:50)

215 nm 2008 [ 24 ]

9. Bovine obestatin API; antibodies 3 impurities C18, 250 mm × 4.6 mm,

5 µ m

Eluent A: H 2 O (0.1%

formic acid); Eluent

B: ACN (0.1% formic

acid); gradient

196,

230

and

296 nm

2008

[

25

]

10. Budesonide Tablets; steroid 10 impurities C18, 125 mm × 4.6 mm,

5 µ m

ACN:phosphate

buffer (pH 3.2, 28.6

mM) (30:70)

240 nm 2008 [ 26 ]

11. Canine obestatin API; antibodies 9 impurities C18, 250 mm × 4.6 mm,

5 µ m



B: ACN (0.1% formic

acid); gradient

196, 230 and

296 nm

2008 [ 25 ]

12.

Carvedilol

Tablets;

antihypertensive

5

impurities

C18,

100

mm

× 4.6

mm,

5

µ m

ACN:phosphate

buffer

(pH

2.5;

0.01

M) (40:60)

240

nm

2008

[

27

]

13. Clindamycin

palmitate HCl and

clindamycin

API; antibiotic 12 impurities C18, 250 mm × 4.6 mm,

5 µ m

CH 3

COONH 4

buffer:MeOH

(15:85)

226 nm;

LC / MS / MS

2008 [ 28 ]

14. Clopidogrel API; antiplatelet 5-[1-(2-Chlorophenyl)-2-

methoxy-2-oxoethyl]-6,7-

dihydrothieno[3,2-c]

pyridin-5-ium

C8, 250 mm × 4.6 mm, 5

µ m

Eluent A: ACN:

potassium

phosphate buffer

(pH 2.3, 10 mM)

(20:80); Eluent B:

ACN: potassium

phosphate buffer

(pH

2.3;

10

mM)

(80:20); gradient

220 and 300

nm

LC / MS / MS

2008 [ 29 ]

15. Dexamethasone Dexamethasone-coated

eluting stents; steroid

Process impurities and

degradants

C8, 4.6 mm × 250 mm, 5

µ m

HCOONH 4

(20 mM,

pH 3.8):ACN;

gradient

239 nm 2008 [ 30 ]

16.

Dimethyl-4,4

- dimethoxy-

5,6,5 ,6 -

dimethylene

dioxy-biphenyl-

2,2 -dicar-

boxylate

(DDB)

API;

hepatoprotective

5

degradants

C18,

250

mm

× 4.6

mm 5 µ m

ACN:H

2

O

(60:40)

235

nm

2008

[

31

]

17. Donepezil HCl API and tablet;

anti-Alzheimer

4 impurities of side

reaction and degradation

C18, 250 mm × 4.6 mm,

5 µ m

Phosphate buffer (5

mM, pH 3.67):

MeOH; gradient

270 nm 2008 [ 32 ]

18. Econazole nitrate Cream; antifungal 4-Chlorobenzyl alcohol

and

α -(2,4-dichloro-phenyl)

-1 H -imidazole-1-ethanol)

C18, 300 mm × 3.9 mm,

10 µ m

MeOH: H 2 O;

gradient

220 nm 2008 [ 33 ]

8/9/2019 1-s2.0-S0731708513003099-main (2).pdf

5/25


Table 2

Continued

S.

no. Name of drug

Matrix; therapeutic

category Impurity / degradant Column / stationary phase Mobile phase Detection

Year

[Ref.]

19. Enalapril maleate API; antihypertensive 5 degradants C18, 250 mm × 4.6 mm,

5 µ m

ACN: phosphate

buffer (pH 3);

gradient

210 nm 2008 [ 34 ]

20. Epirubicin HCl Injection; antibiotic 3 degradation impurities C18, 250 mm × 4.6 mm,

5 µ m

Eluent A: 0.1% TFA

Eluent B: ACN:

MeOH:TFA

(80:20:0.1);

gradient

254 nm 2008 [ 35 ]

21. Fenofibrate Tablets;

anti-hyperlipidemic;

Acid and alkali degraded

impurity of each

C18 (BEH), 100 mm ×

2.1 mm, 1.7 µ m

ACN:CH 3

COONH 4

buffer (10 mM, pH

4.7); gradient

247 nm 2008 [ 36 ]

22. Fluorapacin API and injection;

anticancer

2 related substances C2, 250 mm × 4.6 mm, 5

µ m

ACN:H 2 O (85:15) 218 nm 2008 [ 37 ]

23. Gatifloxacin API; antibacterial 10 related substances C18, 250 mm × 4.6 mm,

5 µ m; C18, 150 mm × 6

mm, 5 µ m; C18, 250 mm

× 4. 6 mm, 5 µ m

TEA (1%, pH

4.3):ACN (87:13)

200–500 nm 2008 [ 38 ]

24. Glimepiride API; antidiabetic 5 degradants C8, 150 mm × 4.6 mm, 5

µ m

ACN: CH 3 COONH 4 (20

mM,

pH

3)

(20:80)

235 nm 2008 [ 39 ]

25. Human obestatin API; antibodies 4 impurities C18, 250 mm × 4.6 mm,

5 µ m

Eluent A: H 2

O (0.1%


B: ACN (0.1% formic

acid); gradient

196, 230 and

296 nm

2008 [ 25 ]

26. Levothyroxine API; thyroid hormone 8 impurities C2, 250 mm × 4.6 mm, 5

µ m

Eluent A: TFA

(0.1%); Eluent B:

ACN; gradient

223 nm 2008 [ 40 ]

27. Lopinavir API; anti-HIV 8 related impurities C18, 250 mm × 4.6 mm,

5 µ m

KH 2 PO 4 (0.02 M, pH

2.5): ACN; gradient

210 nm 2008 [ 41 ]

28.

Methamphetamine

API; psychostimulant 29 impurities Capillary, 30 m × 0.32

mm

× 1. 0

µ m

Nitrogen gas GC-FID 2008 [ 42 ]

29. Mildronate API; antiischemic 6 related impurities Amino, 100 mm × 3.2

mm, 3 µ m; cyano, 100

mm × 2. 1 mm, 5 µ m;

silica, 100 mm × 2.1

mm, 3 µ m; sulfobetaine,

100

mm

× 2.1

mm,

5

µ m

ACN:HCOONH 4

(5

mM, pH 5) (85:15)

Electrospray

interface

detector

2008 [ 43 ]

30. Montelukast

sodium

API; antiallergic 4 impurities C18, 100 mm × 4.6 mm,

3 µ m

Eluent A: Na 2 HPO 4 buffer (50 mM, pH

3.7): ACN (4:1);

Eluent A: Na 2 HPO 4 buffer (50 mM, pH

3.7):

ACN

(1:4);

gradient

225 nm 2008 [ 44 ]

31. Mouse obestatin API; antibodies 3 impurities C18, 250 mm × 4.6 mm,

5 µ m

Eluent A: H 2

O

(HCOOH 0.1%);

Eluent B: ACN

(HCOOH 0.1%);

gradient

196, 230 and

296 nm

2008 [ 25 ]

32. Moxifloxacin API; antibacterial 4 related substances C18, 250 mm × 4.6 mm,

5 µ m; C18, 150 mm × 6

mm, 5 µ m; C18, 250 mm

× 4. 6 mm, 5 µ m

Eluent A: TEA (1%,

pH 2.5):MeOH

(70:30); Eluent B:

phosphate buffer

(pH 2.5):ACN

(85:15);

gradient

200–500 nm 2008 [ 45 ]

33. Ovine obestatin API; antibodies 5 impurities C18, 250 mm × 4.6 mm,

5 µ m

Eluent A: H 2

O

(HCOOH 0.1%);

Eluent B: ACN

(HCOOH 0.1%);

gradient

196, 230 and

296 nm

2008 [ 25 ]

34. Paclitaxel API; anticancer 10-Deacetylbaccatin III,

baccatin III, 10-deacet-yl-

7-xylosyltaxol C,

photo-degradant, taxol C,

ceph-alomannine,

10-deacetyl-7-epitaxol,

7-Epi-taxol

Phenyl, 150 mm × 4.6

mm, 3 µ m

H 2 O:ACN (52:48) 227 nm 2008 [ 46 ]

8/9/2019 1-s2.0-S0731708513003099-main (2).pdf

6/25


Table 2

Continued

S.

no. Name of drug

Matrix; therapeutic


Year

[Ref.]

35.

Phenylethanolamine

derivatives

API; antiasthamatic 11 impurities ASH, 250 mm × 4.6 mm,

5 µ m

n-

Hexane:gthanol:TEA

(98:2:0.1)

254 nm 2008 [ 47 ]

36.

Pipecuronium

bromide

Powder

for

injection;

steroid

4

impurities

Cyano,

250

mm

× 4.6

mm, 5 µ m Tetramethylammonium

hydroxide (4.53 g / L,

pH 6.4):ACN (6:4)

Electrochemi-

cal

detection

2008

[

48

]

37.

Pridinol

mesylate

API;

muscle

relaxant

2

degradant

C18,

250

mm

× 4.6

mm,

5 µ m MeOH:IPA:potassium

phosphate (50 mM,

pH 6.0) (51:9:40)

220

nm

2008

[

49

]

38. Primaquine

phosphate

API; antimalarial 2 impurities C18 (BEH), 50 mm × 2.1

mm, 1.7 µ m

TFA (0.01%):ACN

(75:25)

265 nm 2008 [ 50 ]

39. Primaquine

phosphate

API; antimalarial 2 impurities C18, 250 mm × 4.6 mm,

5 µ m

TFA (0.01%): ACN

(75:25)

265 nm 2008 [ 50 ]

40. Salicylaldehyde

isonicotinoyl

hydrazone

API; chelating agent 2 -Hydroxy-acetophen-

one, Isonicotinoyl

hydrazone, 2 -hydroxy

propiophenone

Isonicotinoylhydrazone

C18, 250 mm × 4.6 mm,

5 µ m

Phosphate buffer

(10 mM + 2 mM

EDTA, pH 6):MeOH

(40:60)

LC–ESI-MS 2008 [ 51 ]

41.

Tamsulosin

Capsule,

tablet

and

API;

antihypertensive 9

process

impurities

C18,

250

mm

× 4.6

mm,

5 µ m CH

3

COONH

4

(10

mM):ACN; gradient 280

nm

2008

[

52

]

42. Tazarotene API; anti-Acne 2 by-product Capillary, 30 m × 0.25

mm, 0.25 µ m

Helium gas MS detection 2008 [ 53 ]

43. Tenatoprazole API; peptic ulcer 6 degradants C18, 250 mm × 4.6 mm,

5 µ m

MeOH:acetate

buffer (10 mM, pH

4.5) (55:45)

306 nm 2009 [ 54 ]

44. Levofloxacin API; antibacterial 3 process related

impurities and 1 oxidative

degradant

C18, 250 mm × 4.6 mm,

5 µ m

Eluent A: NaH 2 PO 4 (25 mM) + 0.5%

TEA (pH 6); EluentB:

MeOH; gradient

294 nm 2009 [ 55 ]

45.

Aalicylic

acid

and

betamethasone

dipropionate

Lotion;

anti-inflammatory

Salicylic

acid

related:

7

betamethasone

dipropio-nate related: 15

potential leachables: 5

C8,

150

mm

× 4.6

mm,

4

µ m

Methanesulfonic

acid:ACN (0.05%);

gradient

240

nm

2009

[

56

]

46. Anastrozole Tablet; anti-cancer 5 impurities C3, 250 mm × 4.6 mm, 5

µ m

H 2

O:ACN; gradient 215 nm 2009 [ 57 ]

47.

Biapenem

API;

antibiotic

4

impurities

C18,

4.6

mm

× 150

mm,

5 µ m CH

3

COONH

4

(1

mM): ACN; gradient 220

nm

2009

[

58

]

48. Chloroquine and

hydroxychloro-

quine

API; antimalarial 4 process related

impurities

C18, 250 mm × 4.6 mm,

5 µ m

TFA

(0.06%):ACN:IPA

(87:12:1)

220 nm 2009 [ 59 ]

49. Citalopram API; antidepressant 1 impurity C18, 100 mm × 30 mm 5

µ m

NH 3 :H 2 O:ACN

(0.1:50:50)

225 nm 2009 [ 60 ]

50. Cyclosporin A Soft gelatin capsules;

Immunomodulator

4 degradants and 2 related

compounds

C18, 250 mm × 4 mm, 5

µ m

THF:phosphoric

acid (0.05M) (44:56)

220 nm 2009 [ 61 ]

51. Diacerein API; antiarrtheritis 2 related impurities C18, 250 mm × 4.6 mm,

5 µ m

Acetic acid

(0.10%):ACN (53:

47)

254 nm 2009 [ 62 ]

52. Eletriptan API; antimigraine 1 degradants (oxidative) C18, 150 mm × 3.9 mm,

5 µ m

MeOH:H 2 O + TEA

(1%) (30:70) (pH

6.52)

225 nm 2009 [ 63 ]

53. Fatty alcohol

ethoxylates

Surfactant 6 impurities C1, 4.6 mm × 150 mm Eluent A:

H 2 O:MeOH (80:20);

Eluent B: MeOH;

gradient

ELSD

detector

2009 [ 64 ]

54. Gentamicin API; antibiotic 33 related impurities Hydro-RP, 250 mm ×

4.6 mm, 5 µ m

Eluent A: MTFA

(50m, pH 2); Eluent

B: MeOH; gradient

ESI / MS n

detection

2009 [ 65 ]

55. Heparin sodium API; anticoagulant 6 impurities AS11-HC, 250 mm × 4

mm, 9 µ m

Eluent A: H 2 O;

Eluent B: NaCl (2.5

M + 20 mM Tris,

pH 3); gradient

215 nm 2009 [ 66 ]

56. Ibuprofen API; analgesic 3-[4-(2-

Methylpropyl)phenyl]propanoic

acid

ZirChrom-CARB, 150 mm

× 4.6 mm, 5 µ m; C18,

150 mm × 4.6 mm, 5

µ m;

Zr-PS,

150

mm

×

4.6

mm,

5

µ m;

C18, 150

mm × 3.0 mm, 7 µ m

ACN:phosphate

buffer (25 mM, pH

2.1) (40:60)

220 and 285

nm

2009 [ 67 ]

8/9/2019 1-s2.0-S0731708513003099-main (2).pdf

7/25


Table 2

Continued

S.

no. Name of drug

Matrix; therapeutic


Year

[Ref.]

57. Icofungipen API; antifungal (1R,2S)-2-(Cinnamyl

amino) -4-methylene

cyclopentane carboxylic

acid

C18, 100–5 AB ACN:H 2 O (25:75) 210 and 254

nm

2009 [ 68 ]

58.

Lamivudine

API;

anti-HIV

5

degradants

C18,

250

mm

× 4.6

mm,

5 µ m Eluent

A:

MeOH;

Eluent B:

CH 3

COONH 4

buffer

(10 mM, pH4);

gradient

277

nm

2009

[

69

]

59. Lansoprazole API; peptic ulcer 5 enantiomers and related

impurities

Chiral, 250 mm × 4.6

mm

Methyl-tert-butyl

ether:ethyl

acetate:ethanol

diethylamine

(60:40:5:0.1)

310 nm 2009 [ 70 ]

60. Metformin Tablet; antidiabetic Related compound:

1-cyanoguanidine

Nova-Pak silica, 150 mm

× 3. 9 mm, 4 µ m

NH 4 H 2 PO 4 buffer:MeOH

(21:79) ̀

232 nm 2009 [ 71 ]

61. Moxifloxacin HCl API; antibacterial 4 synthesis-related

impurities

C18, 50 mm × 4.6 mm, 5

µ m

H 2

O + TEA

(2%):ACN 90:10 (pH

6.0)

290 nm 2009 [ 72 ]

62. Nevirapine

analogue

API; anti-HIV 3 impurities Cyano, 4.6 mm × 150

mm,

5

µ m

Eluent A: H 2 O

(HCOOH

0.1%); Eluent B: ACN

(HCOOH 0.1%);

gradient

ESI / MS n

detection

2009 [ 73 ]

63. Nimodipine Tablet;

antihypertensive

3 impurities C8, 250 mm × 4.6 mm, 5

µ m

ACN:H 2 O

(67.5:32.5)

236 nm 2009 [ 74 ]

64. Norethisterone Tablet; steroid 19-Norandrostenedione C18, 50 mm × 2.1 mm, 5

µ m

MeOH:H 2 O (53:47) ESI / MS n

detection

2009 [ 75 ]

65. Phenazopyridine

HCl

API; analgesic 3-Phenyl-5-phenylazo-

pyridine-2,6-diamine

C3, 250 mm × 4.6 mm, 5

µ m

H 2

O:ACN (25:75) 254 nm 2009 [ 76 ]

66. Pridinol mesylate API, tablet, injection,

Patches;

antihypertensive

3-Piperidino-propiophen-

one, hydrochloride,

1-(3,3-diphenylprop-2-en-

1-yl)piperidine

C18, 250 mm × 4.6 mm,

5 µ m

Potassium

phosphate buffer

(50 mM, pH

6.4):MeOH:2-

propanol

(20:69:11)

245 nm 2009 [ 77 ]

67. Puerarin Injection; vasodilator 9 impurities C18, 250 mm × 4.6 mm,

5 µ m

Formic acid (0.1%):

MeOH; gradient

250 nm 2009 [ 78 ]

68.

Rizatriptan

benzoate

API;

antimigraine

Rizatriptan-1,2-dimer

and

Rizatriptan-2,2-dimer

C8,

250

mm

× 4.6

mm,

5

µ m

Ammonium

dihydrogen

ortho-phosphate

(20 mM) + 2 ml

TEA (pH 2): ACN;

gradient

225

nm

2009

[

79

]

69. Ropinirole HCl API; anti-Parkinsons 4-[2-

(Dipropylamino)ethyl]-

1 H -indol-2,3-dione

X-Bridge TM , 3 mm × 100

mm, 3.5 µ m

ACN:sodium

heptane sulfonate

(5 mM) (21.6:78.4)

(pH 2)

250 nm 2009 [ 80 ]

70. Salidroside API; antidepressant 3 impurities C18, 150 mm × 4.6 mm,

5 µ m

MeOH:H 2 O (13:87) 275 nm 2009 [ 81 ]

71. Sertraline API; antidepressant 9 impurities C18, 250 mm × 4.6 mm,

5

µ m

TFA (0.4%):ACN

(80:20)

225 nm 2009 [ 82 ]

72. Taranabant API; anti-obesity 6 impurities C18, 250 mm × 4.6 mm,

5 µ m

H 3

PO 4

in H 2

O

(0.1%):ACN;

gradient

220 nm 2009 [ 83 ]

73.

Tropicamide

API;

ophthalmology

3

impurities

C18,

150

mm

× 4.6

mm,

5 µ m MeOH:H

2

O

(30:70)

225,

247

and

257 nm 2009

[

84

]

74. Valsartan API; antihypertensive 5 impurities C18, 250 mm × 4.6 mm,

5 µ m

Elunent A:

CH 3 COONH 4 (10

mM, pH 3.0) Eluent

B: H 2 O:ACN (1:4);

gradient

210 nm 2009 [ 85 ]

75.

Zafirlukast

API;

antiasthamatic

5

impurities

C18,

250

mm

× 4.6

mm,

5 µ m

Eluent

A:

phosphate

buffer + 1-decane

sulfonic acid

sodium (pH 4):

MeOH (85:15);

Eluent B:

ACN:MeOH:H 2 O

(85:10:5)

220

nm

2009

[

86

]

76. Zotarolimus Coated stents;

immunomodulator

3 degradant C8, 250 mm × 4.6 mm, 5

µ m

CH 3 COONH 4 (10

mM, pH 3.8): ACN;

gradient

278 nm 2009 [ 87 ]

8/9/2019 1-s2.0-S0731708513003099-main (2).pdf

8/25


Table 2

Continued

S.

no. Name of drug

Matrix; therapeutic


Year

[Ref.]

77. 10- O -(N,N-

dimethyl

aminoethyl)-gink-

golide

B

methane

sulfonate

API; antiplatelet 2 impurities C18, 250 mm × 20 mm,

5 µ m

MeOH:H 2 O (55:45) 210 nm 2010 [ 88 ]

78. Acetazolamide API; diuretics 1 degradant and 4

process-related impurities

C18, 250 mm × 4.6 mm,

5 µ m

Eluent A: NaH 2 PO 4 (0.02M,

pH

3.0):ACN

(950:50);

Eluent B: H 2

O:ACN

(150:850); gradient

254 nm 2010 [ 89 ]

79. Acetylspiramycin API; antibiotics 17 impurities

(process-related,

degradant and starting

materials)

C18, 250 mm × 4.6 mm,

5 µ m

ACN:CH 3

COONH 4

(0.1 M, pH 7.2)

(50:50)

232 nm 2010 [ 90 ]

80. Albuterol sulfate

and ipratropium

bromide

Nasal solution;

anti-asthamatic

Albuterol sulfate related:

8; Ipratropium bromide

related: 5

C8, 250 mm × 4.6 mm, 5

µ m

Eluent A: KH 2 PO 4 +

Heptane-1-sulfonic

acid sodium salt in

H 2 O (pH 4); Eluent

B:

ACN;

gradient

210 nm 2010 [ 91 ]

81.

Alizapride

API;

antiemetic

2

degradants

C18,

150

mm

× 4.6

mm,

5 µ m Eluent

A:

CH 3

COONa buffer

(20 mM, pH 4);

Eluent B: MeOH;

gradient

225

nm

2010

[

92

]

82. Atorvastatin

calcium

API;

anti-hyperlipidemic

4 impurities C18, 150 mm × 4.6 mm,

3.5 µ m

Eluent A: HCOONH 4 (pH 4, 10 mM):ACN

(60:40); Eluent B:

ACN; gradient

246 nm 2010 [ 93 ]

83. Barnidipine API; antihypertensive 4 degradants C18, 250 mm × 4.6 mm,

5 µ m

ACN:phosphate

buffer (pH 7)

(75:25)

250 nm 2010 [ 94 ]

84. Clopidogrel

bisulfate

API and tablet;

antiplatelet

5 impurities Chiral, 250 mm × 4.6

mm, 5 µ m

n-

Hexane:ethanol:diethyl

amine (95:5:0.05)

240 nm 2010 [ 96 ]

85. CU201(antitumor

peptidic dimer)

API; anticancer 11 forced degradants and 3

impurities

C8, 150 mm × 4.6 mm, 3

µ m

Eluent A: H 2

O (0.1%


B:

ACN

(0.1%

Formic

acid), gradient

266 nm 2010 [ 97 ]

86. Desloratadine Tablet; antiallergic 5 impurities and forced

degradants

C18 (BEH), 50 mm × 2.1

mm, 1.7 µ m

Eluent A:

KH 2 PO 4 buffer (10

mM, pH

2.5):MeOH:ACN

(80:15:5);

Eluent

B:

buffer:THF: ACN

(30:5:70)

280 nm 2010 [ 98 ]

87. Duloxetine HCl API; antidepressant 3 related impurities C18, 250 mm × 4.6 mm,

5 µ m

Eluent A: KH 2

PO 4

(10 mM + 0.2%

TEA, pH 2.5); Eluent

B: ACN:MeOH

(20:80); gradient

230 nm 2010 [ 99 ]

88. Enalapril maleate API; antihypertensive Several degradation

impurities

RP-S, 250 mm × 4.6 mm,

5 µ m

Eluent A: phosphate

buffer (20 mM, pH

6.8): ACN (95:5);

Eluent B: phosphate

buffer

(20

mM,

pH

6.8):ACN (34:66);

gradient

215 nm 2010

[ 100 ]

89. Eprosartan API; antihypertensive Impurity: dibenzoic acid C2, 250 mm × 4.6 mm

mm, 5 µ m

Eluent A: TEA buffer

(pH 3); Eluent B:

ACN; gradient

234 nm 2010

[ 101 ]

90. Escitalopram API; antidepressant 3 process-related

impurities

C18, 150 mm × 4.6 mm,

3 µ m

HCOONH 4 (1.5

g / 1000 ml

H 2 O):ACN; gradient

240 nm 2010

[ 102 ]

91. Ezetimibe API;

anti-hyperlipidemic

Process-related impurity C18, 250 mm × 4.6 mm,

5 µ m

H 2 O:ACN; gradient 232 nm 2010

[ 103 ]

92.

Felbamate

API

and

tablets;

antiepileptic

3-Hydroxy-2-phenyl-

propyl

carbamate

and

2-Phenyl-propane-1,3-diol

C18

(BEH),

100

mm

×

2.1

mm,

1.7

µ m

KH 2 PO 4 buffer (pH

3.5):MeOH

(68:32)

210

nm

2010

[

104

]

8/9/2019 1-s2.0-S0731708513003099-main (2).pdf

9/25


Table 2

Continued

S.

no. Name of drug

Matrix; therapeutic


Year

[Ref.]

93. Fentanyl API; analgesic 16 impurities C18, 150 mm × 3.0 mm,

5 µ m

Eluent A: phosphate

buffer (pH 2);

Eluent B: Eluent

A:ACN

(1:1);

gradient

215 nm 2010

[ 105 ]

94. Filgrastim API; hematopoietic

stimulator


µ m

Eluent A: TFA (0.1%)

in ACN:H 2

O;

(10:90); Eluent B:

TFA (0.1%) in

ACN:H 2 O (80:20);

gradient

215 nm 2010

[ 106 ]

95. GW876008

(corticotropin-

release factor 1

antagonist)

API; antidepressant 4 impurities C8, 150 mm × 4.6 mm,

3.5 µ m

Eluent A: H 2 O:TFA

(100:0.05); Eluent

B: MeOH:ACN: TFA

(50:50: 0.05);

gradient

220 nm 2010

[ 107 ]

96. l -Aspartic acid

and l -alanine

API;

food

supplement

Succinic

acid,

citric

acid,

malic acid, maleic acid,

fumaric acid, glycine,

glutamic acid

C3,

150

mm

× 4.6

mm,

5

µ m

MeOH:H 2 O (50:50) CAD

detection

2010

[ 108 ]

97. Omeprazole API and tablets; peptic

ulcer

9 impurities Chiral, 250 mm × 4.6

mm,

10

µ m

Methyl tert-

butylether:ethyl acetate:

ethanol:diethylamine

(60:40:5:0.1)

299 nm 2010

[

109

]

98. Orlistat Capsules; anti-obesity 18 impurities C18, 4.6 mm × 150 mm,

5 µ m

ACN + H 3 PO 4 (0.005%):H 2 O +

H 3 PO 4 (0.005%)

(86:14)

210 nm 2010

[ 110 ]

99. Oxytocin API; uterine stimulant

(hormone)

Acetic acid, carbamido

oxytocin, α -dimer,

acetyl-oxytocin, β-dimer

and five impurities

C18, 250 mm × 4.0 mm,

5 µ m

Eluent A:

ACN:KH 2

PO 4

(pH

4.4):H 2

O

(15:15:70); Eluent

B: ACN:KH 2 PO 4 (pH

4.4):H 2 O (70:

15:15)

220 nm 2010

[ 111 ]

100. Pentoxifylline API; antidiabetic 3 degradants C18, 250 mm × 4.6 mm,

5 µ m

Formic acid

(0.05%):ACN;

gradient

274 nm 2010

[ 112 ]

101.

Piracetam

API;

neurovascular

enhancer

4

impurities

C18,

250

mm

× 4.6

mm,

10

µ m

TEA:ACN

(85:15)

(pH

6.5)

205

nm

2010

[

113

]

102. Pregabalin API and tablet;

antipsychotic


µ m

MeOH:acetate

buffer (10 mM, pH

5.0) (15:85)

345 and 450

nm

2010

[ 114 ]

103. Rabeprazole

sodium

API; peptic ulcer Methylthio impurity of

rabeprazole

C8, 150 mm × 4.6 mm, 5

µ m

Eluent A: phosphate

buffer (pH 7.6):ACN

(98:2) Eluent B:

ACN; gradient

284 nm 2010

[ 115 ]

104. Raltegravir API; anti-HIV 5 impurities C18, 250 mm × 4.6 mm,

5 µ m

H 2 O:ACN:TFA

(0.02%); gradient

240 and 304

nm

2010

[ 116 ]

105. RG7128 (HCV

polymerase

inhibitor)

API; anti-HIV 9 impurities C18, 100 mm × 19 mm,

5 µ m

Formate buffer (10

mM, pH 3.5):ACN;

gradient

276 nm 2010

[ 117 ]

106. Rifaximin API; antibiotic 1 impurity C18, 150 mm × 19 mm,

5 µ m

ACN:MeOH:H 2

O

(36:32:32)

276 nm 2010

[ 118 ]

107. Ritonavir API; anti-HIV 21 degradants C18, 250 mm × 4.6 mm,

5

µ m

H 2

O:MeOH:ACN

(40:20:40)

210 nm 2010

[

119

]

108. Sertraline API; antidepressant 3 non-chiral related

impurities

C18, 150 mm × 4.6 mm,

5 µ m

Phosphate buffer

(10 mM, pH

2.8):MeOH (63:37)

220 nm 2010

[ 120 ]

109. Valsartan API; antihypertensive 7 degradants C18 (BEH), 100 mm ×

2.1 mm, 1.7 µ m

Eluent A: acetic acid

buffer (1%): ACN

(90:10); Eluent B:

acetic

acid

buffer

(1%): ACN (10:90);

gradient

225 nm 2010

[ 121 ]

110. Vestipitant API; antiemetic 3 biphenyl impurities C18, 150 mm × 4.6 mm,

5 µ m

TFA (0.1%) in D 2

O:

TFA (0.1%) in ACN,

gradient

254 nm 2010

[ 122 ]

111. Abacavir API; anti-HIV 8 degradants C18, 250 mm × 4.6 mm,

5 µ m

H 2 O:ACN (90:10) 220 nm 2011

[ 123 ]

112. ALB 109564 API; anticancer 4 impurities C18, 250 mm × 10 mm,

5 µ m


TFA) Eluent B: ACN

(0.1%

TFA)

215 nm 2011

[ 124 ]

8/9/2019 1-s2.0-S0731708513003099-main (2).pdf

10/25


Table 2

Continued

S.

no. Name of drug

Matrix; therapeutic


Year

[Ref.]

113. Anastrozole API; anticancer 3 degradant C3, 100 mm × 4.6 mm, 3

µ m

HCOONH 4 (10

mM):ACN (60:40)

215 nm 2011

[ 125 ]

114.

Artemisinin

API;

antimalarial

Artemisitene,

9-epi-artimisinin

C18,

150

mm

× 2.1

mm,

5 µ m

ACN:H 2 O (60:40) +

0.1% formic acid

DAD

/

MS

2011

[ 126 ]

115. Atazanavir sulfate API; anti-HIV 13 process impurities and

degradants

C8, 150 mm × 4.6 mm, 3

µ m

Eluent A: H 2 O:0.025

M CH 3 COONH 4 ;

Eluent

B:

ACN;

gradient

250 nm 2011

[ 127 ]

116. Auraptene API; immunomodulator 5 impurities C18, 150 mm × 4.6 mm,

5 µ m

H 2

O:ACN; gradient 324 nm 2011

[ 128 ]

117. Boron

phenylalanine

API; anticancer 4 impurities C18, 150 mm × 4.6 mm,

5 µ m

Eluent A:TFA:H 2 O:

MeOH (0.1:85:15);

Eluent B: MeOH;

gradient

230, 256 and

270 nm

2011

[ 129 ]

118. Candesartan

cilexetil

API; antibiotics Process related impurity Cyano, 250 mm × 4.6

mm, 5 µ m

TFA (pH 3):ACN;

gradient

210 nm 2011

[ 130 ]

119. Carbamazepine API; antiepileptic 7 impurities Cyano, 250 mm × 4.6

mm, 5 µ m

THF:CH 3 OH:H 2 O

(3:12:85)

230 nm 2011

[ 131 ]

120.

Casopitant

mesylate

API;

antidepressant

and

antiemetic

De-fluorinated

casopitant

mesylate

analogue

C18,

150

mm

× 4.6

mm,

3.5

µ m

Eluent

A:

H 2 O +

0.2%

NH

4

OH;

Eluent

B: ACN + 0.2%

NH 4

OH; gradient

LC

/

MS

/

MS

2011

[

132

]

121. Ciclesonide API and metered dose

inhalers;

antiasthamatic


10 µ m

Ethanol:H 2

O

(70:30)

242 nm 2011

[ 133 ]

122. Colistin

(Polymyxin E)

API; antibiotic 35 impurities C18, 250 mm × × 4.6

mm, 5 µ m

ACN:sodium sulfate

(4.46 mM, pH 2.3)

(20:80) + 10%

phosphoric acid;

gradient

215 nm 2011

[ 134 ]

123.

Entacapone

API;

anti-Parkinsons

4

forced

degradants

C18,

250

mm

× 4.6

mm,

5 µ m; C3, 250 mm × 4.6

mm, 5 µ m

Potassium

phosphate buffer

(30 mM, pH

2.75):MeOH (50:50)

310

nm

2011

[ 135 ]

124. Etimicin sulfate API; antibiotic 6 impurities C18, 150 mm × 4.6 mm,

5 µ m

Eluent A: H 2

O:NH 3

(25%):CH 3 COOH

(96:3.6:0.4);

Eluent

B: MeOH; gradient

ELSD 2011

[ 136 ]

125. Ezetimibe API;

anti-hyperlipidemic

5 degradation and

process-related impurities

C18, 150 mm × 4.6 mm,

5 µ m

Eluent A: TFA

(0.05%):MeOH

(49:51); Eluent B:

ACN:Eluent A (3:1);

gradeint

210 and 235

nm

2011

[ 137 ]

126. Febuxostat API; anti-gout 4 impurities C18, 150 mm × 4.6 mm,

5 µ m

Eluent A:

CH 3

COONH 4

(10 m

M, pH 3.5); Eluent

B: ACN; gradient

315 nm 2011

[ 138 ]

127. Fesoterodine API; antispasmodic 5 degradants C18, 100 mm × 4.6 mm,

5 µ m ACN:MeOH:CH 3 COONH 4 (30 mM, pH 3.8)

(30:15:55)

208 nm 2011

[ 139 ]

128. G004

(hypo-glycaemic

agent)

API; antidiabetic 4 related impurities C18, 250 mm × 4.6 mm,

5 µ m

Acetic acid (0.1%) +

TEA (0.1%):MeOH

(20:80)

233 nm 2011

[ 140 ]

129.

Gentamicin

API;

antibiotic

5

impurities

C18,

50

mm

× 4.6

mm,

1.8 µ m

Eluent

A:

TFA

(0.1%

pH 2.5); Eluent B:

TFA (0.1% pH 2.5 +

TEA Eluent C: ACN;

gradient

ESI

/

MS

n

detection

2011

[ 141 ]

130. Lactic acid Sugarcane juice;

humectants


5 µ m

NH 4 H 2 PO 4 (20 mM,

pH 2.2)

210 nm 2011

[ 142 ]

131. Larotaxel API; anticancer 5 Related impurities C18, 250 mm × 4.6 mm,

5 µ m


[ 143 ]

132. Lincomycin and

spectinomycin

API; antibiotic Lincomycin related

impurities: 4 and

spectino-mycin

related

impurities:

5

C18, 50 mm × 4.6 mm,

1.8 µ m

TFA (0.05%, pH

3.0):ACN (90:10)

ESI / MS n

detection

2011

[ 141 ]

8/9/2019 1-s2.0-S0731708513003099-main (2).pdf

11/25


Table 2

Continued

S.

no. Name of drug

Matrix; therapeutic


Year

[Ref.]

133. Lornoxicam API; analgesic Degradants C18, 250 mm × 4.6 mm,

5

µ m

KH 2

PO 4

buffer (10

mM,

pH

3.3):MeOH;

gradient

MS detector 2011

[

144

]

134. Memantine Tablets; anticancer Maillard reaction

impurities

Hydro RP, 100 mm × 3

mm, 2.5 µ m

Heptafluoro buturic

acid (0.6%):ACN:

isopropyl

alcohol:H 2 O;

gradient

CAD

detection

2011

[ 145 ]

135. Meprobamate API; antipsychotic Carbamic acid-2-

carbamoyloxymethyl-2-

methyl-pent-3-enyl

ester

C18, 250 mm × 4.6 mm,

5 µ m

H 2 O:ACN (8:2) 200 nm 2011

[ 146 ]

136. Mometasone

furoate

API; steroid 8 impurities C18, 250 mm × 4.6 mm

mm, 5 µ m


[ 147 ]

137. Mometasone

furoate


5 µ m; 2-ethyl-pyridine:

250 mm × 4. 6 mm, 5

µ m;Cyano: 250 mm ×

4.6 mm, 5 µ m

Carbon dioxide (SFC

grade)

245 nm 2011

[ 147 ]

138. Naproxen API; analgesic 2-(6-Methoxynaphtha-

len-2-yl)acrylic

acid

C18, 100 mm × 4.6 mm,

5 µ m

CH 3 COONa (40 mM,

pH 4.7):MeOH

(60:40)

254 nm 2011

[ 148 ]

139. Olanzapine API and drug product;

antipsychotics


µ m

EDTA disodium salt

dihydrate

(50

mM,

pH

3):ACN

(6:4)

220 nm 2011

[

149

]

140. Olanzapine API and tablet;

antipsychotics

8 degradants C18 (BEH), 100 mm ×

2.1 mm, 1.7 µ m

Eluent A: NaH 2

PO 4

(20 mM) buffer (pH

6.8): ACN: MeOH

(5:2:3) Eluent B:

H 2 O: ACN (1:9)

250 nm 2011

[ 150 ]

141. Olaquindox API; anti-amoebic 12 degradants C18, 150 mm × 2 mm, 5

µ m

HCOOH (0.1%):

ACN; gradient

200–400 nm 2011

[ 151 ]

142. Palonosetron HCl API; antiemetic 9 degradants π Nap, 250 mm × 4. 6

mm, 5 µ m

Eluent A: Phosphate

buffer (20 mM + 2

ml TEA, pH 2.5);

Eluent

B:

phosphate

buffer:

ACN

(50:50);

gradient

210 nm 2011

[ 152 ]

143. Perindopril

tert-butylamine

API; antihypertensive 4 impurities C4, 4.6 mm × 250 mm, 5

µ m

Butyl acetate

(0.24%) + ethyl

acetate (0.30%) +

SDS (2%) +

n-butanol (7.75%)

+ dihydrogen

phosphate (20 mM,

pH 3.7)

215 nm 2011

[ 153 ]

144. Phosphorothioate

oligonucleotides

API; diagnostic agent 5 synthesis impurities C18 (BEH), 1 mm × 150

mm,

3.5

µ m

Eluent A: TEA (16

mM)

+

HFIP

(400

mM,

pH

7.0)

in

H 2 O;

Eluent B: TEA (16

mM) + HFIP (400

mM) in MeOH;

gradient

LC–MS / MS 2011

[

154

]

145.

Polymyxin

B

API;

antibiotic

38

impurities

C18,

250

mm

× 4.6

mm, 5 µ m

ACN:sodium

sulfate (4.46 g / l, pH 2.3)

(20:80) + 10%

phosphoric acid

215

nm

2011 [ 134 ]

146. Streptomycin

sulfate

API; antibiotic 21 impurities YMCPack Pro, 250 mm ×

4.6 mm; 3 µ m

PFPA (20 mM):

acetone (99:1)

CAD / MS

Detection

2011

[ 155 ]

147.

Sulindac

API;

analgesic

E-sulindac,

sulfide

and

sulfone form

C18,

53

mm

× 7

mm,

1.5

µ m

ACN:

phosphate

buffer (pH 2, 10

mM); gradient

340

nm

2011

[ 156 ]

148. Ursodeoxycholic

acid

API; billiary cirrhosis 5 related impurities C18, 150 mm × 4.6 mm,

5 µ m

Acetic acid: MeOH

(0.1%) (30:70)

RI detection 2011

[ 157 ]

149. Valsartan API; antihypertensive 2 photodegradant Cyano, 250 mm × 4.6

mm, 5 µ m

ACN: KH 2 PO 4 (20

mM, pH 3) (40:60)

226 nm 2011

[ 158 ]

8/9/2019 1-s2.0-S0731708513003099-main (2).pdf

12/25


Table 2

Continued

S.

no. Name of drug

Matrix;

therapeutic


Year

[Ref.]

150.

Zafirlukast

API;

antiasthamatic

8

impurities

C18,

250

mm

× 4.6

mm,

5 µ m

Eluent

A:

phosphate

buffer + 1-decane

sulfonic

acid

sodium (pH 4):

MeOH (85:15);

Eluent B:

ACN:MeOH:H 2 O

(85:10:5); gradient

220

nm

2011

[ 159 ]

151. Rapamycin API; immunomodulator 9 degradant Diol-120-NP, 250 mm ×

4.6 mm, 5 µ m

Hexanes:2-

propanol;

gradient

278, 248, 230

and 210 nm

2012

[ 160 ]

152. 4-Methyl

thioamphetamine


mm,

0.25

µ m

Helium Mass

selective

detector

2012

[

161

]

153. Halobetasol

propionate

API; steroids Acetamide and

arylsulfonate

C18, 100 mm × 2.10

mm, 2.6 µ m

ACN:H 2

O; gradient 230, 220 and

205 nm

2012

[ 162 ]

154. Artemisinin Artemisia annua

extracts; antimalarial

Extract residue impurities C18, 250 mm × 4.6 mm,

5 µ m

ACN:H 2

O:MeOH

(50:30:20)

192, 200,

205, 210 and

215 nm

2012

[ 163 ]

155. Atorvastatin

calcium

API;

anti-hyperlipidemic


3.5 µ m

Eluent A: phosphate

buffer (pH 5.4);

Eluent B: ACN:THF

(90:10); gradient

220 nm 2012

[ 164 ]

156. Azelnidipine Solution;

anti-hypertensive


3

µ m

Eluent A: KH 2 PO 4 (15

mM):ACN:MeOH

(8:1:1) Eluent B:

ACN; gradient

220 nm 2012

[

165

]

157. Benzopyrido-

oxathiazepine

API; anticancer 10 degradants C18, 150 mm × 2.1 mm,

3 µ m

ACN:H 2

O (60:40) +

0.1% formic acid

318 nm 2012

[ 166 ]

158. Bupropion

hydrochloride

API and tablets;

Anti-depressant

Alkaline degradates,

3-chlorobenzoic acid

C18, 4.6 mm × 150 mm,

5 µ m

NH 4 H 2 PO 4 (1.2%,

pH 4.5):ACN (80:20)

210 nm 2012

[ 167 ]

159. Caffeine API; stimulant 4 impurities C18, 150 mm × 4.6 mm,

5 µ m, 29 columns;

Others, 150 mm × 4. 6

mm mm, 5 µ m, 6

columns

THF:ACN:CH 3 COONH 4 (pH 4.5) (40:50:10)

275 nm 2012

[ 168 ]

160.

Cefditoren

pivoxil

API

and

tablet;

Antibiotic 1

degradants

C18,

250

mm

× 4.6

mm;

5 µ m ACN:H

2

O

(50:50)

218

nm

2012

[ 169 ]

161. Clocortolone

pivalate


5 µ m

ACN:H 2

O (70:30) 254 nm 2012

[ 170 ]

162. Cloperastine

fendizoate

API; cough relaxant Methyl p-toluene

sulfonate and 2-chloro

ethyl p-toluene sulfonate

C8, 250 mm × 4.6 mm, 5

µ m

Phosphate buffer

(10 mM, pH

3.0):MeOH with

10% ACN (45:55)

227 nm 2012

[ 171 ]

163. Deferasirox API; Antidote of Iron 2-[3,5-Bis(2-hydroxy-

phenyl)-[1,2,4]-triazol-1-

yl]-benzoic

acid

C8, 250 mm × 4.6 mm, 5

µ m

Eluent A:H 2 O:TFA

(100:0.05); Eluent

A: ACN:MeOH:TFA

(50:50:0.05)

gradient

LC–ESI-QT /

MS / MS

2012

[ 172 ]

164. Desvenlafaxine API and tablet;

Antidepressant

1 degradants (acid) C18, 250 mm × 4.6 mm,

5 µ m

TEA (0.2%)

+ CH 3

COONH 4

(50

mM, pH 6.5):MeOH

(40:60)

228 nm 2012

[ 173 ]

165.

Diltiazem

HCl

API

and

tablet; Anti-hypertensive

6

related

substances

C18,

150

mm

× 4.6

mm, 5.0 µ m

TEA

(0.2%):ACN; gradient

240

nm

2012 [ 174 ]

166. Dipyridamole API; antiplatelet 2 impurities C2, 150 mm × 4.6 mm, 5

µ m

Eluent A: KH 2 PO 4 buffer (10 mM, pH

7.0):MeOH (50:50);

Eluent B:

MeOH:KH 2 PO 4 (10

mM) buffer; (95:5);

gradeint

295 nm 2012

[ 175 ]

167. Eslicarbazepine

acetate

API; antiepileptic 15 impurities C8, 250 mm × 4.6 mm, 5

µ m

Eluent A: KH 2

PO 4

(10 mM, pH 5): ACN

(95:5); Eluent B:

ACN:H 2 O (80:20);

gradient

215 nm 2012

[ 176 ]

8/9/2019 1-s2.0-S0731708513003099-main (2).pdf

13/25


Table 2

Continued

S.

no. Name of drug

Matrix; therapeutic


Year

[Ref.]

168. Esomeprazole

magnesium

Tablets, pepetic ulcer 7 impurities C18 (BEH), 50 mm × 2.1

mm, 1.7 µ m

Eluent A: glycine

buffer (40 mM, pH

9);

Eluent

B:

ACN:H 2 O (90:10);

gradient

305 nm 2012

[ 177 ]

169. Etimicin sulfate API; antibiotic 26 impurities C18, 250 mm × 4.6 mm,

5

µ m

Eluent A: H 2 O:NH 3 (25%):CH

3 COOH

(96:3.6:0.2); Eluent

B: MeOH; gradient

ESI / MS n

detection

2012

[

178

]

170. Fampridine API; agent multiple

sclerosis

Isoniacin, niacin,

Isonico-tinamide,

3-aminopyridine, 2-amino

pyridine,

famp-ridine-N-oxide,

3-hydr-oxy-4-amino

pyridine

C18, 250 mm × 4.6 mm,

5 µ m

Eluent A: 1-octane

sulfonic acid

sodium (10 mM) +

CH 3 COONH 4 (10

mM) + 0.1% TEA

(pH 4):MeOH

(95:5); Eluent B:

MeOH; gradient

240 and 282

nm

2012

[ 179 ]

171. Glucocorticoids API; steroid 4-Dimethyl aminopyridine C18, 50 mm × 2 mm, 3

µ m


formic

acid);

Eluent

B:

ACN

(0.1%

formic

acid); gradient

190–400 nm 2012

[

180

]

172. Guaifenesin,

terbutaline sulfate

and ambroxol HCl

Cough syrup; cough

relaxant

13 related substances C18, 250 mm × 4.6 mm,

5 µ m

Eluent A: NH 4

H 2

PO 4

(20 mM) +

1-heptane sulfonic

acid sodium salt

buffer (1%) (pH

2.6):ACN:MeOH

(95:4:1); Eluent

B:ACN NH 4 H 2 PO 4 (20 mM) +

1-heptane

sulfonic

acid sodium salt

buffer (1.0%) (pH

9.5) (6:4); gradient

222 nm 2012

[ 181 ]

173. Imatinib mesylate Capsules; anticancer 8 impurities C18 (BEH), 50 mm × 2. 1

mm, 1.7 µ m

Eluent A:

CH 3 COONH 4 (50

mM,

pH

9.5);

Eluent

B: ACN:MeOH

(40:60); gradient

237 nm 2012

[ 182 ]

174. l -Alanyl- l -

glutamine

API; food supplement 5 impurities C18, 150 mm × 3 mm, 3

µ m



B: ACN (0.1% formic

acid);

gradient

ESI / MS n

detection

2012

[ 183 ]

175. l -Alanyl- l -

glutamine

Infusion solution; food

supplement

9 impurities Polysulfoethyl A, 150

mm × 4. 6 mm, 5 µ m

Eluent A: NH 4

OH

(100 mM): H 2

O

(1:9); Eluent B:

NH 4

OH (100 mM):

ACN (1:9); gradient

ESI / MS n

detection

2012

[ 183 ]

176. l -Alanyl- l -

glutamine


supplement

7 impurities QN-AX, 150 mm × 4

mm, 5 µ m

CH 3 COONH 4 (20

mM, pH 4.5):ACN

(60:40)

ESI / MS n

detection

2012

[ 183 ]

177. l -Alanyl- l -

glutamine


supplement

7 impurities QN-AX, 150 mm × 4

mm 5 µ m

Eluent A: formic

acid buffer (100

mM, pH 3.5):H 2 O

(1:9);

Eluent

B:

formic acid buffer

(100 mM, pH

3.5):ACN (1:9);

gradient

ESI / MS n

detection

2012

[ 183 ]

178. Linezolid API; antibiotic 6 impurities Chiral, 250 mm × 4.6

mm, 5 µ m

ACN:ethanol:n-

butyl amine:TFA

(96:4:0.10:0.16)

254 nm 2012

[ 184 ]

179. Luliconazole API and cream;

antifungal


5 µ m

MeOH:H 2 O (80:20) 296 nm 2012

[ 185 ]

180.

Methamphetamine


mm

× 1. 0

µ m

Helium gas Mass

selective

detector

2012

[

186

]

8/9/2019 1-s2.0-S0731708513003099-main (2).pdf

14/25


Table 2

Continued

S.

no. Name of drug

Matrix; therapeutic


Year

[Ref.]

181. Moxonidine Tablet; antihpertensive 5 impurities C18, 250 mm × 4.6 mm,

5 µ m

MeOH:potassium

phosphate buffer

(50 mM), (15:85)

(pH 3.5)

255 nm 2012

[ 187 ]

182. Nevirapine API; anti-HIV 2 impurities ABZ, 150 mm × 4.6 mm,

5

µ m

Ammonium

phosphate

buffer

(50 mM, pH

4.5):ACN (7:3)

220 nm 2012

[

188

]

183. Niacinamide API; vitamin Niacin, isonicotinamide,

picolinamide,

3-cyano-pyridine,

niacinamide N-oxide

C18, 250 mm × 4.6 mm,

5 µ m

CH 3

COONH 4

(20

mM, pH 5):ACN

(97:3)

254 nm 2012

[ 189 ]

184. Nonpeptide

(angiotensin AT1

receptor

antagonist)

API; antihypertensive 4 impurities C18, 250 mm × 4.6 mm,

5 µ m

Phosphoric acid (pH

3.5):ACN (51:49)

210 nm 2012

[ 190 ]

185. Pantoprazole API; peptic ulcer 2-Chloromethyl-3,4-

dimethoxy

pyridine

HCl

C18, 50 mm × 4.6 mm, 3

µ m

CH 3 COONH 4 (10

mM):ACN

(79:21)

210 nm 2012

[

191

]

186. Plazomicin API; antibiotic 3 impurities C18, 4.6 mm × 150 mm,

3.5 µ m

NH 4

OH (25

mM):ACN; gradient

210 nm 2012

[ 192 ]

187. Praziquantel API andTablet;

Anthelmintic

2 impurities Silica, 4.0 mm × 125

mm, 100 / 5 µ m

ACN:CH 3

COONH 4

(25 mM) (40:60)

210 nm 2012

[ 193 ]

188.

Rivastigmine

tartrate API;

anti-Alzheimer

11

impurities

C18,

250

mm

× 4.6

mm,

5 µ m Eluent

A:

KH

2

PO

4

(10 mM, pH

7.6):ACN (90:10);

Eluent B:

ACN:MeOH (60:40);

gradient

210

nm

2012

[ 194 ]

189.

Ropinirole

API;

anti-Parkinsons

5

degradants

Silica

gel

60F-254

Toluene:ethyl

acetate:NH 3 (6 M)

(5:6:0.5)

250

and

254

nm

2012

[ 195 ]

190. SCD: chalcone

derivative

Nanoemulsion;

antiprotozoal

2 degradants C18, 150 mm × 4 mm, 5

µ m

MeOH:H 2

O (70:30)

(pH 5,TFA)

330 nm 2012

[ 196 ]

191. Sodium

tanshinone IIA

sulfonate

API; antioxidant 8 impurities C18, 250 mm × 4.6 mm,

5 µ m

CH 3 COONH 4 (0.2%):MeOH

(35:65)

271 nm 2012

[ 197 ]

192. Telmisartan API; antihypertensive Methyl

4 ,4 -dibromometh-yl

biphenyl-2-carboxylate

C18, 125 mm × 4.6 mm,

5 µ m

KH 2 PO 4 +

sodium-1-pentane

sulfonate (pH 3)

230 nm 2012

[ 198 ]

193.

Thiocolchicoside

API;

muscle

relaxant

6

degradants

C18,

250

mm

× 4.6

mm,

5

µ m

Ammonium

formate

buffer

(10

mM; pH 3):ACN;

gradient

MS

/

MS

Detection

2012

[

199

]

194. Trandolapril API; antihypertensive 16 degradants C18 (BEH), 138 mm ×

2.1 mm, 1.7 µ m

Ammonium

hydrogen carbonate

(10 mM, pH

8.14):ACN (68:32)

190 and 500

nm

2012

[ 200 ]

195. Wogonin API; anxiolytic 2 degradants C18, 250 mm × 4.6 mm,

5 µ m

MeOH:CH 3 COONH 4 buffer (5 mM)

(75:25)

275 nm 2012

[ 201 ]

196. Zolmitriptan API; antimigraine 6 impurities Phenyl, 100 mm × 3

mm,

2.7

µ m

KH 2 PO 4 (20 mM) +

sodium

1-hexan

sulfonate

(5

mM,

pH

2):ACN; gradient

220 nm 2012

[

202

]

197. Bortezomib API; anticancer 3 impurities C18, 250 mm × 4.6 mm,

5 µ m

Eluent A:

HCOOH:ACN:H 2

O

(1:300:700); Eluent

B: HCOOH:ACN:H 2 O

(800:200:1);

gradient

270 nm 2012

[ 203 ]

2.1.2. 2009

2.1.2.1.

Impurity

profiling Both techniques of LC–MS, ion trap mass

spectrometry and time of flight mass spectrometry were used

for characterization of impurities in chloroquine and hydroxy-

chloroquine bulk drug samples [ 59 ]. 1-(1,1-Bis(4-fluorophenyl)-

1,3-dihydroisobenzofuran-5-yl)-4-(dimethylamino) butan-1-one hy-

drobromide as an impurity of citalopram was isolated by semi-

preparative HPLC and structure was established by using Q-TOF

mass analyzer, NMR and IR spectroscopy. Overlaid FT-IR spectra

has shown ( Fig. 3 ) that structure of impurity and drug related

to each other with difference of peak at 1681 cm −1 and 2229

cm −1 from C O and C N, respectively [ 60 ]. Principally, cy-

closporin A is used as immunosuppressive agent for prophylaxis

against allograft rejection after organ transplantation. Impurities of

this agent in Neoral ®

capsules and its generic versions were deter-

mined [ 61 ]. Two monoacylated diacerein impurities of diacerein with

same molecular weight ( M W = 326) but different position of acetyl

8/9/2019 1-s2.0-S0731708513003099-main (2).pdf

15/25


Fig. 3. Overlaid FT-IR spectra of (a) citalopram and (b) citalopram impurity-II. (Reuse

with

the

permission

of

Elsevier

Limited,

The

Boulevard,

Langford

Lane,

Kidlington,

Oxford OX5 1GB, UK.)

group was confirmed by NMR spectroscopy, which were character-

ized as 5-acetoxy-4-hydroxy-9,10-dioxo-9,10-dihydroanthracene-2-

carboxylic acid (1.14%) and 4-acetoxy-5-hydroxy-9,10-dioxo-9,10-

dihydroanthracene-2-carboxylic acid (1.24%) [ 62 ]. Polyethylene gly-

col (PEG) present as impurity in fatty alcohol ethoxylates (FAEs) which

are used as surfactants. Gradient elution favor the separation of PEG and FAEs as these have dramatic difference in hydrophobicity of

PEG and FAEs, while evaporative light scattering detection (ELSD)

is not compactable with gradient elution, so both isocratic and gra-

dient elution were used to study the same [ 64 ]. Atmospheric pres-

sure chemical ionization (APCI) of mass spectroscopy was applied for

identification of gentamicin impurities, where no suppression in ion-

ization was observed at high TFA concentration [ 65 ]. Over sulfated

chondroitin sulfate (OSCS) and dermatan sulfate were estimated in

heparin API by using a polymer-based strong anion exchange (SAX)

column with gradient elution form, which were present due to over

sulfati

Documents

1-s2.0-S0731708513003099-main (2).pdf