Facile and manifest spectrophotometric methods for the determination of six quinolone antibiotics in...

ORI GINAL RESEARCH

Facile and manifest spectrophotometric methodsfor the determination of six quinolone antibioticsin pharmaceutical formulations using iron salts

Farhan Ahmed Siddiqui • M. Saeed Arayne •

Najma Sultana • Agha Zeeshan Mirza •

Faiza Qureshi • M. Hashim Zuberi

Received: 3 May 2009 / Accepted: 15 September 2009 / Published online: 11 November 2009

� Birkhauser Boston 2009

Abstract Simple spectrophotometric methods have been developed for the deter-

mination of six quinolone antibiotics, namely, ciprofloxacin, gatifloxacin, norflox-

acin, levofloxacin, ofloxacin, and pefloxacin, in pharmaceutical formulations using

three different salts of iron. These methods are based on the formation of complexes

with ferric nitrate, ferric chloride, or iron ammonium citrate in which the carboxylic

group of quinolones undergoes complexation with iron. The complexes formed in

these reactions, having a brown color, were measured at their respective kmax values.

The increase in absorbance was directly proportional to the concentration of quin-

olones and obeys Beer’s law in the range of 6–300 lg mL-1 (r C 0.9999). The

proposed methods were optimized and validated per the guidelines of the Interna-

tional Conference on Harmonization. The proposed methods were successfully

employed for determination of these quinolones in pharmaceutical formulations.

Keywords Ciprofloxacin � Gatifloxacin � Norfloxacin � Levofloxacin �Ofloxacin � Pefloxacin

Introduction

Quinolones or fluoroquinolones constitute a large class of synthetic antimicrobial

agents that are highly effective in the treatment of many types of infectious diseases,

F. A. Siddiqui (&) � M. S. Arayne � A. Z. Mirza � F. Qureshi � M. H. Zuberi

Department of Chemistry, University of Karachi, Karachi 75270, Pakistan

e-mail: [email protected]; [email protected]

M. S. Arayne

e-mail: [email protected]

N. Sultana

Research Institute of Pharmaceutical Sciences, Faculty of Pharmacy, University of Karachi, Karachi

75270, Pakistan

Med Chem Res (2010) 19:1259–1272

DOI 10.1007/s00044-009-9268-7

MEDICINALCHEMISTRYRESEARCH

particularly those caused by bacteria. They are widely used to treat human and

veterinary diseases (Currie et al., 1998; Ihrke et al., 1999; Chen et al., 1999). Due to

the fluorine atom at position C-6 and the piperazine or methyl piperazine at position

C-7, these antibiotics exhibit a broad spectrum of activity against Gram-positive and

Gram-negative bacteria. Over time, bacteria become resistant to medicines that are

used to combat them; because of this, the medical world is always in search of new

and improved ways to battle these disease-causing bacteria. New antibiotics are

continually being developed and quinolones are at the forefront of this research

(Wolfson and Hooper, 1989; Carlucci, 1998).

Several analytical methods for quantitative determination of quinolones in

pharmaceutical formulations are described in the literature, including capillary

electrophoresis (Flurer, 1997; Sun and Chen, 1997; Bhowal and Das, 1991) and UV

spectrophotometry (Venugopal and Saha, 2005). Spectrophotometric analysis of

gatifloxacin was done using the latter method, but different buffers were used;

however, in our case no buffer was used, so the method has an advantage over the

previous one. In a method reported by Fratini and Schapoval (1996), the Lambert-

Beer law was obeyed in the concentration range of 20–100 lg mL-1, and also nitric

was used, but in the newly developed method the linearity range is much broader

and, also, the limit of quantification is much less than in this previous work,

titrimetry (British Pharmacopoeia, 1999; Belal et al., 1999), and high-performance

liquid chromatography (HPLC) (Samanidou et al., 2003; Joshi, 2002; Sanzgiri et al.,1994). Some authors prepared derivatives of different quinolones and compared

their properties against those of quinolone (Shaharyar et al., 2007; Gopalakrishnan

et al., 2007; Jayashree et al., 2009); and the in vitro availability of atorvastatin, in

the presence of ciprofloxacin, gatifloxacin, and ofloxacin has been reported (Arayne

et al., 2009).

The objective of this research was to develop and validate rapid, economical, and

sensitive methods for quantitative determination of six quinolones—ciprofloxacin

(Fig. 1), gatifloxacin (Fig. 2), norfloxacin (Fig. 3), levofloxacin/ofloxacin (Fig. 4),

and pefloxacin (Fig. 5)—in bulk and tablet formulations using different salts of iron.

The major advantage of the proposed methods is that these six flourquinolones can

be determined on a single system with minor modifications in detection wavelength.

The proposed methods were applied successfully to determination of the six

HN

N N

F

O

COOH

Fig. 1 Ciprofloxacin

1260 Med Chem Res (2010) 19:1259–1272

quinolones in both reference material and dosage forms with high values of

accuracy and precision. No interference was observed in the assay from common

excipients at levels found in pharmaceutical formulations. These methods were

validated by the statistical data. In addition, the association constant, stochiometric

ratio of reactants, and standard free energy changes (DG�) were determined.

Fig. 2 Gatifloxacin

NN

HN

O

HOOCF

CH3Fig. 3 Norfloxacin

N

N

F

N

OH3C

O

CH3

COOH

Fig. 4 Levofloxacin/ofloxacin

Med Chem Res (2010) 19:1259–1272 1261

Experimental

Instrumentation

A double-beam UV–vis spectrophotometer (Shimadzu model 1601) equipped with

10-mm quartz cells was used to make absorbance measurements and Shimadzu

UVPC version 3.9 software was used to control the instrument, data acquisition, and

data analysis. Spectra of quinolone–iron complexes were recorded over the

wavelength range 360–800 nm.

Chemicals

All chemicals used were of analytical grade; demineralized double-distilled water

was used throughout the study. Ciprofloxacin, gatifloxacin, norfloxacin, levoflox-

acin, ofloxacin, and pefloxacin were kind gifts from local pharmaceutical

companies. Pharmaceutical formulations were purchased from the market and

ferric chloride, ferric nitrate, and iron ammonium citrate were from Merck,

Germany.

Preparation of standard solutions

Reference stock solutions of ciprofloxacin, gatifloxacin, norfloxacin, levofloxacin,

and pefloxacin were prepared in water at a concentration of 500 lg mL-1, whereas

ofloxacin at the same concentration was prepared in methanol. These stock solutions

were diluted to obtain the desired concentration ranges for different quinolones (5–

200 lg mL-1 for ciprofloxacin, 10–250 lg mL-1 for gatifloxacin, 6–300 lg mL-1

for norfloxacin, 10–200 lg mL-1 for levofloxacin, ofloxacin, and pefloxacin).

Preparation from pharmaceutical formulations

Twenty tablets of each formulation were weighed and powdered. A powdered tablet

equivalent to 50 mg of active substance was transferred to a 100-ml volumetric flask

NN

N

O

COOH

H3C

F

CH3

Fig. 5 Pefloxacin

1262 Med Chem Res (2010) 19:1259–1272

and diluted up to the mark with the same solvent as mentioned for the standard

preparation. These solutions were stirred on a magnetic stirrer for 60 min, filtered,

and further diluted to obtain the desired concentration ranges. All solutions were

stored at 4�C. One percent solutions of ferric chloride, ferric nitrate, and iron

ammonium citrate were prepared in double-distilled water.

Quinolone complexes with ferric chloride

To prepare 10–200 lg mL-1 ciprofloxacin, gatifloxacin, ofloxacin, and pefloxacin,

10–160 lg mL-1 levofloxacin, and 6–300 lg mL-1 norfloxacin, different aliquot

portions of reference standard solutions of each drug were transferred into separate

series of 25-ml volumetric flasks. In each flask, 3 ml of 1% ferric chloride solution

was successively added. The volume was made up to the mark with water and set

aside at room temperature for 10 min. The absorbance of quinolone–iron complexes

was measured against a reagent blank at 375, 473, 442, 375, 375, and 434 nm for

ciprofloxacin, gatifloxacin, norfloxacin, levofloxacin, ofloxacin, and pefloxacin,

respectively. The calibration graph was prepared by plotting absorbance versus

concentration of drugs (Table 1).

Table 1 Linear regression functions and their statistical parameters

Drug k Regression equation r SE LOD

(lg mL-1)

LOQ

(lg mL-1)

With FeCl3

Ciprofloxacin 375 A = 0.0107 Cx ? 0.0667 0.9951 0.1599 0.022 0.066

Gatifloxacin 473 A = 0.0021 Cx – 0.0079 0.9952 0.6632 0.445 1.347

Norfloxacin 442 A = 0.0066 Cx – 0.0041 0.9999 0.1549 0.106 0.321

Levofloxacin 375 A = 0.0139 Cx ? 0.0459 0.9980 0.5142 0.050 0.153

Ofloxacin 375 A = 0.0123 Cx ? 0.091 0.9950 0.5098 0.171 0.517

Pefloxacin 434 A = 0.0050 Cx – 0.0487 0.9998 0.2233 4.574 13.86

With C6H8O7FeNH3


Gatifloxacin 360 A = 0.0109 Cx – 0.0052 0.9996 0.1515 0.043 0.129

Norfloxacin 432 A = 0.0072 Cx – 0.0257 0.9952 0.2154 0.745 2.258

Levofloxacin 375 A = 0.0072 Cx – 0.0174 0.9958 0.6566 1.329 4.026

Ofloxacin 360 A = 0.0135 Cx ? 0.0364 0.9971 0.3684 0.311 0.942

Pefloxacin 426 A = 0.0031Cx ? 0.0085 0.9963 0.5846 0.527 1.596

With FeNO3


Gatifloxacin 447 A = 0.0041 Cx ? 0.5307 0.9951 0.2707 0.250 0.757

Norfloxacin 445 A = 0.0061 Cx ? 0.0007 0.9995 0.2333 0.497 1.507

Levofloxacin 375 A = 0.0137 Cx ? 0.051 0.9985 0.3269 0.698 2.116

Ofloxacin 370 A = 0.0135 Cx ? 0.0273 0.9975 0.2987 0.319 0.952

Pefloxacin 434 A = 0.0049 Cx ? 0.0056 0.9998 0.2846 0.143 0.432

SE standard error

Med Chem Res (2010) 19:1259–1272 1263

Quinolone complexes with ferric nitrate and iron ammonium citrate

Assays were completed for the formation of complexes of quinolones with ferric

nitrate (using 3 ml of a 1% solution) and iron ammonium citrate (using 1 ml of a

1% solution) as mentioned for ferric chloride.

Results and discussion

Iron(III) salts have been shown to be ideal for the derivatization of carboxylic

groups (Franch et al., 2004; Arayne et al., 2008), which makes them a suitable

reagent for detection and quantification of quinolones via their carboxylic group.

Fe3? holds three molecules of quinolone, resulting in the complex having a brown

color which absorbs radiation in the visible range. In this article, the development

and validation of sensitive and precise spectrophotometric methods for determina-

tion of six quinolones, using this derivatization technique, have been described.

Optimization of derivatization conditions

The optimum reaction conditions for quantitative determination of all quinolones

were established via a number of preliminary experiments. The concentration of

iron(III) was optimized by using 1–5 ml of a 1% iron solution. Steady and

maximum color development of the complex was achieved with a volume of 3 ml

of ferric chloride and ferric nitrate, but in the case of iron ammonium citrate the best

results were observed when 1 ml of salt solution was used. Hence 3 ml of 1% ferric

chloride and ferric nitrate solutions and 1 ml of 1% iron ammonium citrate solution

were used as the optimal concentrations for validation of the method.

Calibration curves

Calibration curves were prepared by linear least squares regression analysis plotting

of the absorbance of quinolone–iron complexes versus the concentration of

quinolone (6–300 lg mL-1) (Table 1).

Reaction of quinolone with ferric chloride

An intense brown color developed in the visible region, showing minor bands at 360

and 440 nm for all quinolones except gatifloxacin, which exhibited absorption at

445 nm (Fig. 6) when the solutions of quinolones were mixed with ferric chloride

solution individually. These bands were attributed to the formation of a quinolone–

iron complex, in which three quinolone rings bind to iron(III).

Reaction of quinolone with ferric nitrate and iron ammonium citrate

An intense brown color developed in the visible region at 360 and 440 nm (Figs. 7

and 8) when solutions of different quinolones were mixed with ferric nitrate and

1264 Med Chem Res (2010) 19:1259–1272

iron ammonium citrate. These bands have been attributed to the formation of a

quinolone–iron complex, which is formed by three quinolone rings and iron.

These visible spectrophotometric methods, using aqueous solutions of iron(III)

ions as reagents, have an elegant simplicity; a brownish-green complex was formed

in the proportion 3:1 [quinolone:iron(III)]. The optimized methods were validated

for quinolone–iron complexes in pharmaceutical formulations. Results were of

adequate precision and accuracy. The absorption spectra obtained revealed that all

the quinolones showed almost the same behavior, except for gatifloxacin. In

reaction with ferric chloride, all quinolones show the same curve except for

gatifloxacin (Fig. 6); two bands were found in all quinolones except gatifloxacin,

one at 360 nm, whereas gatifloxacin showed maxiumum absorbance at 440 nm. A

similar trend was observed in the case of iron ammonium citrate and ferric nitrate

(Figs. 7 and 8).

Fig. 6 UV spectra of quinolone/FeCl3 complexes: (a) ciprofloxacin; (b) gatifloxacin; (c) levofloxacin;(d) norfloxacin; (e) ofloxacin; (f) pefloxacin

Fig. 7 UV spectra of quinolone/ferric ammonium citrate complexes: (a) ciprofloxacin; (b) gatifloxacin;(c) levofloxacin; (d) norfloxacin; (e) ofloxacin; (f) pefloxacin

Med Chem Res (2010) 19:1259–1272 1265

Association constants and standard free energy changes

The absorbance of the complex was used to calculate the association constant using

the Benesi–Hildebrand (Benesi and Hildebrand, 1949) equation:

Ca=A ¼ 1=eð Þ þ 1=Kc�eð Þ � 1=Cbð Þ

where Ca and Cb are the concentrations of the acceptor and donor, respectively, A is

the absorbance of the complex, e is the molar absorptivity of the complex, and Kc is

the association constant of the complex. The calculated association constants are

reported in Table 2. The low values of Kc are common in these complexes due to

dissociation of the complex to the radical anion.

The standard free energy changes of complexation (DG�) were calculated from

the Kc values by the following equation (Martin et al., 1969):

DG� ¼ �2:303RT logKc

where DG� is the free energy change of the complex (kJ mol-1), R the gas constant

(1.987 cal mol-1 deg-1), T the temperature in Kelvin (273 ? �C), and Kc the

association constant of quinolone–iron complexes (l mol-1).

Validation of methods

Linearity, limits of detection and quantification, and stability

Linearity of the assay was demonstrated by at least six concentrations over the range

6–300 lg mL-1 for six quinolones. Absorbances were plotted against concentra-

tions and analyzed using least squares linear regression (Table 1). According to ICH

recommendation the detection and quantification limits of the methods were

calculated using the standard deviation of the response and the slope of calibration

curve as reported in Table 1.

Fig. 8 UV spectra of quinolone/FeNO3 complexes: (a) ciprofloxacin; (b) gatifloxacin; (c) levofloxacin;(d) norfloxacin; (e) ofloxacin; (f) pefloxacin

1266 Med Chem Res (2010) 19:1259–1272

Precision and accuracy were assessed in conjunction with the linearity

studies using three spiked samples of three concentrations of each quinolone.

Measured concentrations were determined by application of the appropriate

standard curve obtained on each occasion. Precision was assessed in terms of

percentage RSD values. Percentage recovery values were used to express

accuracy (Table 3).

Sensitivity and interference study

The percentage recovery values of quinolones confirm the high sensitivity of the

proposed methods. The excellent recoveries indicate the absence of interference

from frequently encountered excipients. Percentage RSD values were B3.89

(Table 3). Under the same experimental conditions different excipients at different

concentrations were added and analyzed. Potential interference problems from the

commonly used excipients and other additives such as microcrystalline cellulose,

lactose, povidone, starch, and magnesium stearate were examined, and it was

confirmed that the excipients did not interfere with the assay. Low percentage RSD

values signify good precision of the method.

Table 2 Association constants

and standard free energy

changes

Drug DG Kc log Kc

Ferric chloride

Ciprofloxacin –0.349 1.80 0.256

Norfloxacin –0.348 1.79 0.255

Pefloxacin –0.349 1.80 0.256

Levofloxacin –0.350 1.81 0.259

Ofloxacin –0.350 1.81 0.259

Gatifloxacin –0.346 1.79 0.254

Ferric nitrate


Norfloxacin –0.584 2.68 0.428

Pefloxacin –0.586 2.69 0.429


Ofloxacin –0.590 2.70 0.430


Iron ammonium citrate


Norfloxacin –0.776 3.71 0.570

Pefloxacin –0.777 3.71 0.570


Ofloxacin –0.781 3.74 0.573


Med Chem Res (2010) 19:1259–1272 1267

Ta

ble

3A

ccu

racy

and

pre

cisi

on

of

pro

pose

dm

eth

od

FeC

l 3C

6H

8O

7F

eNH

3F

eNO

3

Ad

ded

(lg

mL

-1)

Rec

over

ed(%

)%

RS

DA

dd

ed(l

gm

L-

1)

Rec

ov

ered

(%)

%R

SD

Ad

ded

(lg

mL

-1)

Rec

over

ed(%

)%

RS

D

Cip

rofl

ox

acin

51

00

.10

.10

10

10

5.2

3.6

11

01

00

.70

.49

10

10

0.0

0.0

02

01

03

.02

.07

20

98

.51

.10

20

10

4.0

2.7

54

01

02

.21

.53

40

10

3.8

2.6

6

60

99

.70

.18

80

99

.40

.41

60

10

0.2

0.1

1

10

09

9.9

0.0

91

20

99

.80

.16

10

01

00

.60

.45

14

01

00

.70

.50

16

09

9.9

0.0

81

40

99

.20

.55

17

01

00

.20

.16

20

01

00

.60

.40

18

09

9.5

0.3

5

20

01

00

.30

.20

Mea

n0

.51

.18

0.8

2

Gat

iflo

xac

in4

09

9.5

0.3

31

09

9.8

0.1

41

09

9.9

0.0

8

60

10

1.7

1.1

62

01

01

.51

.04

40

10

2.5

1.7

7

80

10

3.8

2.6

64

01

00

.40

.29

60

10

0.1

0.0

9

10

01

00

.00

.00

80

99

.90

.07

10

09

8.4

1.1

3

12

09

9.0

0.6

91

20

97

.02

.17

14

01

00

.00

.01

20

09

7.9

1.5

11

60

97

.61

.74

18

01

00

.10

.05

20

01

04

.73

.27

Mea

n1

.06

1.2

50

.52

No

rflo

xac

in6

10

0.8

0.5

51

09

5.6

3.2

11

09

8.0

1.4

3

20

99

.90

.11

20

99

.40

.45

20

98

.60

.99

40

10

1.3

0.8

84

09

7.8

1.6

14

01

01

.00

.73

60

10

0.6

0.3

98

01

03

.32

.31

80

97

.31

.95

80

10

0.5

0.3

51

20

99

.10

.61

12

01

00

.00

.04

10

01

00

.00

.01

16

09

9.2

0.5

51

60

98

.70

.93

1268 Med Chem Res (2010) 19:1259–1272

Ta

ble

3co

nti

nu

ed FeC

l 3C

6H

8O

7F

eNH

3F

eNO

3

Ad

ded

(lg

mL

-1)

Rec

over

ed(%

)%

RS

DA

dd

ed(l

gm

L-

1)

Rec

ov

ered

(%)

%R

SD

Ad

ded

(lg

mL

-1)

Rec

over

ed(%

)%

RS

D

20

01

00

.70

.52

20

09

8.8

0.8

8

30

01

03

.32

.27

Mea

n1

.26

1.2

50

.99

Lev

ofl

ox

acin

10

10

0.2

0.1

51

01

00

.00

.00

10

10

2.6

1.8

0

40

98

.61

.00

20

99

.60

.29

20

99

.80

.14

60

99

.90

.08

40

10

0.1

0.0

94

01

02

.51

.75

10

01

00

.10

.04

80

10

0.0

0.0

08

09

7.2

1.9

8

14

09

9.6

0.2

81

20

98

.51

.06

12

09

9.9

0.0

5

16

01

00

.60

.44

16

09

9.3

0.4

81

60

10

0.0

0.0

0

20

01

00

.10

.04

Mea

n0

.33

0.2

80

.95

Ofl

oxac

in1

09

9.5

0.3

81

01

01

.30

.90

10

10

0.0

0.0

0

20

10

1.6

1.1

52

01

00

.40

.26

20

98

.31

.21

40

99

.60

.25

40

10

1.2

0.8

74

01

00

.00

.02

60

10

0.1

0.0

48

09

9.2

0.6

18

01

01

.51

.02

12

09

9.4

0.4

41

20

97

.81

.60

12

01

00

.00

.00

16

01

00

.00

.04

16

01

04

.83

.34

16

01

00

.00

.00

20

01

00

.00

.02

20

09

7.2

2.0

1

Mea

n0

.38

1.0

80

.60

Pefl

ox

acin

40

94

.73

.89

10

10

2.4

1.6

71

09

9.4

0.4

1

60

10

1.3

0.8

92

01

00

.00

.00

20

10

0.0

0.0

0

10

01

04

.02

.80

40

10

1.8

1.2

34

01

02

.41

.66

14

01

01

.00

.69

60

99

.30

.52

80

96

.12

.79

Med Chem Res (2010) 19:1259–1272 1269

Ta

ble

3co

nti

nu

ed FeC

l 3C

6H

8O

7F

eNH

3F

eNO

3

Ad

ded

(lg

mL

-1)

Rec

over

ed(%

)%

RS

DA

dd

ed(l

gm

L-

1)

Rec

ov

ered

(%)

%R

SD

Ad

ded

(lg

mL

-1)

Rec

over

ed(%

)%

RS

D

16

09

9.8

0.1

71

00

10

0.0

0.0

01

20

10

1.8

1.2

9

20

09

9.0

0.6

91

40

99

.90

.08

16

01

00

.00

.03

18

01

00

.00

.00

20

01

01

.91

.33

Mea

n1

.52

0.5

01

.07

1270 Med Chem Res (2010) 19:1259–1272

Application in pharmaceutical formulations

The proposed methods were successfully applied to the analysis of quinolones in

commercial formulations. The results were in good agreement with the declared

contents, and no interference was observed in the assay of all quinolones from

common excipients at levels found in pharmaceutical formulations. These methods

rely on the use of simple and inexpensive chemicals and techniques but have a

sensitivity analogous to that obtained by sophisticated and expensive techniques

such as HPLC and are validated by statistical data. The reaction conditions and

application of the methods for determination of quinolones in pharmaceutical

formulations have been established.

Conclusion

It is rare that ferric salts are used as chromogenic reagents for spectrophotometric

determination of these quinolones. The proposed methods, which are simple and

rapid, offer the advantages of sensitivity over a wide range of concentrations

without the need for extraction or heating. The methods do not entail any stringent

reaction conditions and have been successfully applied to the determination of

quinolones in pharmaceutical formulations.

References

Arayne MS, Sultana N, Siddiqui FA, Mirza AZ, Zuberi MH (2008) Spectrophotometric techniques to

determine tranexamic acid; kinetic studies using ninhydrin and direct measuring using ferric

chloride. J Mol Struct. doi:10.1016/j.molstruc.2008.04.026

Arayne MS, Sultana N, Rizvi SBS, Haroon U (2009) In vitro drug interaction studies of atorvastatin with

ciprofloxacin, gatifloxacin, and ofloxacin. Med Chem Res. doi:10.1007/s00044-009-9225-5

Belal F, Al-Majed AA, Al-Obaid AM (1999) Methods analysis 4-quinolone antibacterials. Talanta

50:765–786

Benesi HA, Hildebrand JH (1949) A spectrophotometric investigation of the interaction of iodine with

aromatic hydrocarbons. J Am Chem Soc 71(8):2703–2707

Bhowal SK, Das TK (1991) Spectrophotometric determination of same recently introduced antibacterial

drugs using ferric chloride. Anal Lett 24:25–37

British Pharmacopoeia (1999) British Pharmacopoeia, vol 1. Her Majesty’s Stationary Office, London, pp

69–370, 1034–1035

Carlucci G (1998) Analysis of fluoroquinolones in biological fluids by high-performance liquid

chromatography. J Chromatogr A 812:343–367

Chen DK, McGeer A, Azavedo JCD, Low DE (1999) Decreased susceptibility of Streptococcus

pneumoniae to fluoroquinolones in Canada. N Engl J Med 341:233–239

Currie D, Lynas L, Kennedy DG, McCaughey WJ (1998) Evaluation of modified EC four-plate method to

detect antimicrobial drugs. Food Addit Contam 15:651–660

Flurer CL (1997) Analysis of antibiotics by capillary electrophoresis. Electrophoresis 18:2427–2437

Franch MI, Ayllon JA, Peral J, Domenech X (2004) Fe(III)-photocatalysed degradation of low chain

carboxylic acids. Implication of the iron salt. Appl Catal B Environ 50:89–99

Fratini L, Schapoval EES (1996) Ciprofloxacin determination by visible light spectrophotometry using

iron(III) nitrate. Int J Pharm 127:279–282

Med Chem Res (2010) 19:1259–1272 1271

http://dx.doi.org/10.1016/j.molstruc.2008.04.026

http://dx.doi.org/10.1007/s00044-009-9225-5

Gopalakrishnan M, Thanusu J, Kanagarajan V (2007) Synthesis and biological evaluation of 5,7-diaryl-

4,4-dimethyl-4,5,6,7-tetrahydropyridino[3,4-d]-1,2,3-thiadiazoles. Med Chem Res 16:392–401

Ihrke PJ, Papich MG, Demanuelle TC (1999) The use of fluoroquinolones in veterinary dermatology. Vet

Dermatol 10:193–204

Jayashree BS, Thomas S, Nayak Y (2009) Design and synthesis of 2-quinolones as antioxidants and

antimicrobials: a rational approach. Med Chem Res. doi:10.1007/s00044-009-9184-x

Joshi S (2002) HPLC separation of antibiotics present in formulated and unformulated samples. J Pharm

Biomed Anal 28:795–809

Martin AN, Swarbrick J, Cammarata A (1969) Physical pharmacy, 3rd edn. Lee & Febiger, Philadelphia,

p 344

Samanidou VF, Demetriou CE, Papadoyannis IN (2003) Direct determination of four fluoroquinolones,

enoxacin, norfloxacin, ofloxacin, and ciprofloxacin, in pharmaceuticals and blood serum by HPLC.

Anal Bioanal Chem 375:623–629

Sanzgiri D, Knaub SR, Riley CM (1994) Quantitative determination of gatifloxacin, levofloxacin,

lomefloxacin and pefloxacin fluoroquinolonic antibiotics in pharmaceutical preparations by high-

performance liquid chromatography. Anal Profiles Drug Subst Excipients 23:325–369

Shaharyar M, Ali MA, Abdullah MM (2007) Synthesis and antiproliferative activity of 1-[(sub)]-6-fluoro-

3-[(sub)]-1,3,4-oxadiazol-2-yl-7-piperazino-1,4-dihydro-4-quinolinone derivatives. Med Chem Res

16:292–299

Sun SW, Chen LY (1997) Optimization of capillary electrophoretic separation of quinolone antibacterials

using the overlapping resolution mapping scheme. J Chromatogr A 766:215–224

Venugopal K, Saha RN (2005) New, simple, and validated UV-spectrophotometric methods for the

estimation of gatifloxacin in bulk and formulations. Il Farmaco 60:906–912

Wolfson JS, Hooper DC (1989) Introduction. In: Wolfson JS, Hooper DC (eds) Quinolone antimicrobial

agents. American Society for Microbiology, Washington, DC, pp 1–4

1272 Med Chem Res (2010) 19:1259–1272

http://dx.doi.org/10.1007/s00044-009-9184-x

Facile and manifest spectrophotometric methods for the determination of six quinolone antibiotics in...

Documents

Transcript of Facile and manifest spectrophotometric methods for the determination of six quinolone antibiotics in...