Research Article

DETERMINATION OF LOMEFLOXACIN IN PHARMACEUTICALS USING DIFFERENTIAL PULSE

POLAROGRAPHIC ANALYSIS

1ABDUL AZIZ RAMADAN*, 2HASNA MANDIL

Dept. of Chemistry, Faculty of Sciences, Aleppo University, Syria. 1Email: dramadan@scs-net.org

Received: 17 July 2012, Revised and Accepted: 29 Aug 2012

ABSTRACT

The electrochemical behavior of Lomefloxacin (LFLX) at dropping mercury electrode (DME) in 0.05M Na2HPO4 over the pH range 4.0–11 has been

studied using differential pulse polarographic analysis (DPPA). At 4.0≤pH≤8.5 one reduction peak was observed in the potential range of –1.260 to -

1.350V and at 8.7≤ pH≤10.0 two peaks were observed; the first was in the range of -1.376 to -1.500V while the second was in the range of -1.590 to -

1.594 V. Finally at pH >10.0, only one peak was observed in the range of -1.760 to -1.767V. A simple, precise, inexpensive and sensitive DPPA has

been developed for the determination of LFLX. A linear calibration was obtained in the range of 1.0–100 µmol.L-1 at pH 7.0 and in the range of 4.0–

200 µmol.L-1 at pH 9.25. RSD was less than 3.6% (n=5) at all concentration levels. The method was successfully applied for the determination of

LFLX in pharmaceuticals.

Keywords: Lomefloxacin, Pharmaceuticals, Differential Pulse Polarographic Analysis.

INTRODUCTION

Lomefloxacin (LFLX),[1-ethyl-6,8-difluoro-1,4- dihydro-7-(3-methyl-

1-piperazinyl)-4-oxo-3-quinolinecarboxylix acid], with formula

C17H19F2N3O3, (mw:351.348 g/mol), (or, the maternal is also

available commercial us hydrochloride formed of Lomefloxacin

hydrochloride C17H19F2N3O3.HCl) experimental, (Scheme1), is one of

the synthetic antibacterial fluoroquinolone agents of the third

generation, which exhibits high activity against a broad spectrum of

Gram-negative and Gram-positive bacteria. This material is broadly

medicated for treatment of the urinary tract and respiratory

infections1,2. Various analytical techniques have been utilized for the

determination of Fluorquinolone such as high-performance liquid

chromatography (HPLC)3–8,liquid chromatography–tandem mass

spectrometry10, analytical high performance thin layer

chromatography(HPTLC)11, spectrophotometry12-18, fluorometry19-22

and electrochemical methods23-37. The polarographic analysis was

successfully applied for determination some drugs as Gatifloxacin34,

Carbinoxamine Maleate35, Dipyrone36 and Atorvastatin37.

In the present study, differential pulse polarographic behaviour and

determination of Lomefloxacin in phosphate buffer using dropping

mercury electrode (DME) was applied.

Scheme 1: Chemical structure of Lomefloxacin(A), Lomefloxacin

Hydrochloride(B)

MATERIALS AND METHODS

Reagents

Sodium tetraborate decahydrate (Na2B4O7·10H2O), disodium

hydrogenphosphate (Na2HPO412H2O), sodium hydroxide (NaOH)

and phosphoric acids, were purchased from Merck. Lomefloxacin

was obtained from National Institute for The Control of

Pharmaceutical and Biological Products (Beijing, China). Stock

standard 0.001 mol.L−1 of Lomefloxacin hydrochloride (purity

>99.5%) was prepared by dissolving 38.78 mg standards in double

distilled water. This solution was found to be stable for three

weeks, that if stored at −4◦C in dark flask. Standard working

solutions were prepared by diluting the standard stock solution

just before use. Working standards were prepared daily by

diluting different volumes of stock solution (0.025, 0.050, 0.10,

0.20, 0.30, 0.40, 0.60, 0.80, 1.00, 2.00, 3.00, 4.00 and 5.00 mL) with

12.5 mL supporting electrolyte of disodium hydrogen phosphate

or sodium tetraborate decahydrate, adjusting the pH as required

using in the appropriate volume of phosphoric acid 0.10 mol.L−1 or

sodium hydroxide 0.2 mol.L−1 and then diluting to 25 mL with

double-distilled water. Supporting electrolyte of 0.10 mol.L−1 was

prepared by dissolving 35.814g of Na2HPO4.12H2O or 38.1g of

Na2B4O7·10H2O in 1000 mL volumetric flask using double-distilled

water. All solutions and reagents were prepared with double-

distilled deionised water and analytical grade chemicals. Ultrapure

mercury from Metrohm Company was used throughout the

experiments.

Instruments and apparatus

A Metrohm 797 VA processor. A Metrohm 797 VA stand with a

multi-mode electrode (MME) comprising a dropping mercury

electrode (DME) as a working electrode, an auxiliary platinum

electrode and a reference electrode (Ag/AgCl) saturated with a 3.0

mol.L−1 KCl solution and the three-electrode cell were used. pH–

meter (Radiometer company model Ion Check) was used. All

measurements were done at room temperature 25±2°C. Highly pure

nitrogen gas (99.999%) was used for de-oxygenation.

Analytical procedure

25 mL of working standard of Lomefloxacin was transferred to the

cell. The solution was well mixed by automatic mixer and

deoxygenated with nitrogen gas for 5 min. Current-voltage curves

were recorded. Limiting currents were measured and calibration

curves in electrolytes were constructed.

Sample preparation

Commercial formulations Lomeflox and Quino: Ctd. tab and

Lomoquin: drop, Dalta-flox- Aleppo- Syria, which contain 400

mg/tab. and 0.3% of Lomefloxacin (or 441 mg/tab. and 0.33%

Lomefloxacin.HCl), were used for the analysis of LFLX by the DPP

method. Eight tablets of pharmaceutical formulations Lemoflox and

Quino were weighed and ground to a fine powder. A quantity

equivalent to one tablet was weighed, dissolved in water,

transferred to a 100 mL volumetric flask and diluted to the mark

with water. An accurately volume 0.100 mL sample solution of tablet

or drop was added to 12.5 mL of supporting electrolyte disodium

hydrogen phosphate, adjust to the desired pH (7.0 or 9.25) using

phosphoric acid 0.10 mol.L−1 or sodium hydroxide solution 0.20

mol.L−1, then transferred into a 25 mL standard flask and diluted to

the mark with double-distilled water.

International Journal of Pharmacy and Pharmaceutical Sciences

ISSN- 0975-1491 Vol 4, Suppl 5, 2012

AAAAAAAAccccccccaaaaaaaaddddddddeeeeeeeemmmmmmmmiiiiiiiicccccccc SSSSSSSScccccccciiiiiiiieeeeeeeennnnnnnncccccccceeeeeeeessssssss

Ramadan et al.

Int J Pharm Pharm Sci, Vol 4, Suppl 5, 255-261

256

RESULTS AND DISCUSSION

Effect of pH

The influence of the phosphate buffer solution (pH 4.0 – 11.0) on the peak current (Ip) and peak potential (Ep) were examined. The polarograms of the differential pulse polarographic (DPP) analysis for 40 µmol.L−1 and 80 µmol.L−1 Lomefloxicin hydrochloride in phosphate buffer (in the presence of 0.05 mol.L−1 Na2HPO4) at different pH values using dropping mercury electrode (DME) shown in Fig.1. At pH values between 4.0–8.5, only one reduction peak in the range of potential at –1.260 to -1.350V (Ep1) was observed. Increase the pH within the range shift the Ep1 value to the negative direction, Fig.2(A), with almost constant Ip1 value to pH 7, then decreases sharply, Fig.2(B). At pH values between 8.7–10.0, two reduction peaks were observed, the first peak (Ep1) is in the range of potential at -1.380 to -1.500 V, while the second peak (Ep2) is in the potential ranges at -1.590 to -1.594 V, Fig.2(A). In this pH range the Ip1 > Ip2 and the value of Ip1 decrease. Ip2 increase until pH 9.25 and then decrease after that, Fig.2(B). Finally at pH >10.0, only one peak in the range of potential (Ep2) at -1.758 to -1.770 V was observed, Fig.2(A), and Ip2 sharply increase, Fig.2(B). The shift of E, with pH indicates that the electron uptake is preceded by a proton transfer as proposed earlier for Nalidixic acid, Gatifloxacin and others23, 29-33.

Proposed mechanism for Lomefloxacin reduction at the DME

By comparison with norfloxacin and Gatifloxacin [24, 29-31],

Lomefloxacin (HAN), it is expected to exist in aqueous media with

intermediate pH values (3.0-8.5) as a zwitterion, HAZ, a neutral molecule,

HAN; where, it shows the first peak in accordance to the equation:

HAZ + e → HAZ- (I)

It is expected that, zwitterions, HAZ will be the major existing species

since one of the nitrogen atoms in the piperazine moiety is more

basic than the carboxylate ion, according to the equation (I) (only

first peak appears). In a weak basic medium (8.5≤ pH ≤ 10.0) the

conjugate base HAZ, HAN and A- ; where reduces HAZ according to the

equation (I), first peak, and A-, second peak, accordance to the

following equations:

However, in a strong basic medium (pH > 10) the conjugate base A-

predominates according to the following equation:

In this case only second peak appears according to equation (III). Based on the deferential pulse polarograms in base electrolytes of

wide pH ranges, the appearance or disappearance of peaks

according to pH values of solutions, the above-mentioned proposed

equilibrium, we suggest the reduction of Lomefloxacin at the DME

may take place according to the equations of Scheme 2.

Fig. 1: The effect of pH values on DPP analysis of Lomefloxacin 80µM using DME in phosphate buffer ; polarograms (1 - 14) represent pH

4.0, 5.0, 6.0, 7.0, 7.5, 8.0, 8.5, 9.0, 9.25, 9.50, 9.8, 10.0, 10.5 and 11.0 respectively.

Fig. 2: The effect of pH values on Ep1, Ep2(A) and Ip1, Ip2(B) of Lomefloxacin 80µM using DME in phosphate buffer .

Ramadan et al.

Int J Pharm Pharm Sci, Vol 4, Suppl 5, 255-261

257

Scheme 2: Electrochemical reduction of Lomefloxacin at DME

Effect of pulse amplitude

The effect of pulse amplitude on polarograms of DPP using DME for

the determination of Lomefloxacin in phosphate buffer (pH 7.0 &

9.25) was studied. The peak current Ip increases proportionally with

increasing of pulse amplitude negative polarity (DPPNP) and pulse

amplitude positive polarity (DPPPP) up to the value 100 mV.

Therefore the value of pulse amplitude 90 mV for DPPNP was

chosen as optimum value, see Fig.3.

Effect of electrolyte

The effect of electrolytes (Na2B4O7·10H2O and Na2HPO4.12H2O ) in

the peak current of LFLX was studied . It was found that, the most

suitable electrolyte is Na2HPO4.12H2O . Since the usage of

Na2HPO4.12H2O (0.05M) as an electrolyte gave a higher and sharper

peak than Na2B4O7·10H2O, see Fig.4.

Calibration curves

Calibration curves for the determination of Lomefloxacin by DPP using DME electrodes at pH=7.0 were studied. Only one peak was observed, the peak current (Ip) was proportional to the concentration of Lomefloxacin over the ranges 1.0 – 100 μmol.L−1 (y=-7.464X-13.35, R2=0.9998; y: Ip, nA and X: CLFLX, μmol.L−1). At pH = 9.25, the peak current (Ip1) was proportional to the concentration of Lomefloxacin over the ranges 4.0 – 200 μmol.L−1 (y=-3.390X+12.65, R2=0.9995) and the peak current (Ip2) was proportional to the concentration of Lomefloxacin over the ranges 4.0 – 200 μmol.L−1 (y=-1.621X-7.581, R2=0.9999),see Fig.5 and Tables 1-3. The limit of quantifying LFLX was 1.0 μmol.L−1 for Ip1 at pH 7 and 4.0 μmol.L−1 for Ip1 and Ip2 at pH

9.25 with the relative standard deviation (RSD) of ± 3.6 %,

± 3.8 % and ± 4.2 % respectively.

Ramadan et al.

Int J Pharm Pharm Sci, Vol 4, Suppl 5, 255-261

258

Fig. 3: The effect of pulse amplitude on DPP analysis of Lomefloxacin 80µM using DME: A) Ip1 at pH 7.0, B) Ip1(1) & Ip2(2) at pH 9.25 ; C)

Ip1 at pH 7.0, D) Ip1(1) & Ip2(2) at pH 9.25 (A & B negative pulse and C & D positive pulse).

Fig. 4: The effect of concentration of electrolyte on Ip of Lomefloxacin 80µM using DME:A) Ip1 at pH 7.0; B) Ip1&Ip2 at pH 9.25

Fig. 5: Calibration curves for the determination of Lomefloxacin by DPP with DME: A) at pH 7.0; B) at pH 9.25 (1-Ip1, 2-Ip2).

Ramadan et al.

Int J Pharm Pharm Sci, Vol 4, Suppl 5, 255-261

259

Table 1: Evaluation of accuracy and precision of the proposed methods for determination of lomefloxacin using DME by DPPNP at pH 7

CLFLX taken., ∝∝∝∝M CLFLX. found,

X , µM

SD, µM

Analytical standard error, n

SD

, µM

Confidence limits

X ± n

SD

t, µM

RSD %

1.00 1.00 0.036 0.016 1.00 ± 0.045

3.6

2.00 1.99 0.068 0.030 1.99 ± 0.084

3.4

4.00 4.05 0.122 0.054 4.05 ± 0.151

3.0

8.00 8.00 0.224 0.100 8.00 ± 0.278

2.8

10.00 9.98 0.269 0.121 9.98 ± 0.335

2.7

12.00 11.98 0.288 0.129 11.98 ± 0.370

2.4

20.00 20.15 0.403 0.180 20.15 ± 0.500

2.0

30.00 30.00 0.510 0.228 30.00 ± 0.633

1.7

40.00 39.96 0.599 0.268 39.96 ± 0.744

1.5

80.00 79.98 0.960 0.429 79.98 ± 1.191

1.2

100.0 100.0 1.00 0.447 100.0 ± 1.242

1.0

Table 2: Evaluation of accuracy and precision of the proposed methods for determination of lomefloxacin using DME by DPPNP (Ep1) at pH

9.25

CLFLX taken., µM CLFLX. found,

X , µM

SD, µM

Analytical standard error, n

SD

, µM

Confidence limits

X ± n

SD

t, µM

RSD %

4.00 4.08 0.155 0.069 4.08 ± 0.192

3.8

8.00 8.12 0.284 0.127 8.12 ± 0.353

3.5

10.00 10.04 0.321 0.144 10.04 ± 0.399

3.2

12.00 12.00 0.360 0.161 12.00 ± 0.447

3.0

20.00 19.93 0.558 0.250 19.93 ± 0.693

2.8

40.00 40.21 1.045 0.468 40.21 ± 1.298

2.6

80.00 80.06 1.841 0.824 80.06 ± 2.286

2.3

120.0 120.5 2.53 1.13 120.5 ± 3.14

2.1

160.0 161.4 2.91 1.30 161.4 ± 3.61

1.8

200.0 201.6 3.23 1.44 201.6 ± 4.00

1.6

Table 3: Evaluation of accuracy and precision of the proposed methods for determination of lomefloxacin using DME by DPPNP (Ep2). at

pH 9.25

CLFLX taken., µM CLFLX. found,

X , µM

SD, µM

Analytical standard error, n

SD

, µM

Confidence limits

X ± n

SD

t, µM

RSD %

4.00 4.10 0.172 0.077 4.10 ± 0.214

4.2

8.00 7.97 0.287 0.128 7.97 ± 0.356

3.6

10.00 10.00 0.320 0.143 10.00 ± 0.379

3.2

12.00 11.92 0.358 0.160 11.92 ± 0.444

3.0

20.00 20.40 0.571 0.255 20.40 ± 0.709

2.8

40.00 40.21 1.045 0.468 40.21 ± 1.298

2.6

80.00 80.92 2.023 0.905 80.92 ± 2.512

2.5

120.0 119.8 2.64 1.18 119.8 ± 3.27

2.2

160.0 159.6 3.19 1.43 159.6 ± 3.96

2.0

200.0 201.0 3.62 1.62 201.0 ± 4.49

1.8

Ramadan et al.

Int J Pharm Pharm Sci, Vol 4, Suppl 5, 255-261

260

Table 4: Determination of lomefloxacin in some pharmaceutical formulations using DPPNP methods on DME at pH= 7.0

Commercial

name

Contents,mg

x , mg

RSD% Recovery %

Lomeflox,Ctd.tab.

Balsam.Pharma Co.

(Homs- -Syria)

400mg/tab. 408 2.2 102.0

Quino, Ctd.tab.

Alfares pharmaceuticals Co.

Damascus – Syria

400mg/tab. 404 2.4 101.0

Dalta-flox,Drop

Delta for medicaments

Aleppo – Syria

0.30% 0.31% 2.8 103.3

Lomoquin, Drop

Medico Labs.

(Homs- -Syria)

0.30% 0.32% 2.6 106.6

Table 5: Determination of lomefloxacin in some pharmaceutical formulations using DPPNP methods on DME at pH= 9.25

Commercial

name

Contents,mg

x , mg

RSD% Recovery %

Lomeflox,Ctd.tab.

Balsam.Pharma Co.

(Homs- -Syria)

400mg/tab. 410 2.4 102.5

Quino, Ctd.tab.

Alfares pharmaceuticals Co.

Damascus – Syria

400mg/tab. 406 2.4 101.5

Dalta-flox,Drop

Delta for medicaments

Aleppo – Syria

0.30% 0.30% 3.0 100.0

Lomoquin, Drop

Medico Labs.

(Homs- -Syria)

0.30% 0.32% 2.9 106.6

APPLICATIONS

Many applications for the determination of Lomefloxacin in

pharmaceutical preparations: Lomeflox and Quino :Ctd. tab and

Lomoquin : drop, Dalta-flox- Aleppo- Syria, which contain 400

mg/tab. and 0.3% of Lomefloxacin (or 441 mg/tab. and 0.33%

Lomefloxacin.HCl) using differential pulse polarography in

phosphate buffer at pH 7 and 9.25 on DME were proposed. The

above obtained sample solutions were applied to the differential

pulse polarography determination of Lomefloxacin. The results of

quantitative analysis for Lomfloxacin were calculated by calibration

curves and the standard addition methods, see Tables 4&5.

CONCLUSION

In the proposed method, differential pulse polarographic analysis of

Lomefloxacin in both pure form and pharmaceutical formulations at

pH 7.0 and pH 9.25 over the range of 1.0 – 100 μmol.L−1 at pH 7.0

and in the range of 4.0 – 200 μmol.L−1 at pH 9.25 using DME was

applied. Applying over mentioned methods in this context was

successfully carried out for the first time. The relative standard

deviation (RSD) did not exceed of ± 3.6%, ± 3.8% and ± 4.2 % at

pH 7.0 for Ip1 and pH 9.25 for Ip1and Ip2 respectively. The method

was successfully applied for the determination of LFLX in

pharmaceuticals.

REFERENCES

1. Wang Xu, Zhao Huichun, Nie Lihua, Jin Linpei, Zhang Zhonglun,

Europium sensitized chemiluminescense determination of

rufloxacin. Anal Chimi Acta, 2001; 445: 169–175.

2. Zhanel GG, Noreddin AM., Pharmacokinetics and

pharmacodynamics of the new fluoroquinolones: focus on

respiratory infections. Curr Opin Pharmacol, 2001;1:459-463.

3. Guo-Hui Wan, Hua Cui, Yi-Lan Pan, Ping Zheng, Li-Juan Liu,

Determination of quinolones residues in prawn using high-

performance liquid chromatography with Ce(IV)–Ru(bpy)32+–

HNO3 chemiluminescence detection, J of Chromatography B,

2006; 843:1–9.

4. Shervington LA, Abba M, Hussain B, Donnelly J, The

simultaneous separation and determination of five quinolone

antibotics using isocratic reversed-phase HPLC: Application to

stability studies on an ofloxacin tablet formulation, J of

Pharmaceutical and Biomedical Analysis, 2005; 39: 769–775. 5. Shoulian Wei, Jiesheng Lin, Haifang Li, Jin-Ming Lin, Separation

of seven fluoroquinolones by microemulsion electrokinetic

chromatography and application to ciprofloxacin, lomefloxacin

determination in urine, J of Chromatography A, 2007;

1163:333–336.

6. Santoro MIRM, Kassab NM, Singh AK, Kedor-Hackmam ERM,

Quantitative determination of Gatifloxacin, levofloxacin,

lomefloxacin and pefloxacin fluoroquinolonic antibiotics in

pharmaceutical preparations by high-performance liquid

chromatography, J Pharm Biomed Anal, 2006; 40:179–184.

7. Han-wen Sun, Pan He, Yun-kai Lv, Shu-xuan Liang, Effective

separation and simultaneous determination of seven

fluoroquinolones by capillary electrophoresis with diode-array

detector, J Chromatography B, 2007;852:145–151 .

8. Amin AS, Dessouki HA, Agwa IA, Ion-pairing and reversed

phase liquid chromatography for the determination of three

different quinolones: Enrofloxacin, lomefloxacin and ofloxacin,

Arabian J Chem, 2011; 4:249-257.

9. Mitani K, Kataoka H, Determination of fluoroquinolones in

environmental waters by in-tube solid-phase microextraction

coupled with liquid Chromatography–tandem mass

spectrometry. Anal Chimi Acta, 2006; 562:16-22.

10. Patil M, Tambe V, Vichare V, Kolte R, Validated simultaneous

UV spectrophotometric methods for estimation of ciprofloxacin

and tinidazole in tablet dosage form. Int J of Pharmacy and

Pharm Sci, 2012; 4:182-185.

11. Shah SA, Rathod IS, Savale SS, Patel DB, Determination of

bioequivalence of lomefloxacin tablets using urinary excretion

data, J Pharm Biomed Anal, 2002; 30:1319-1329.

12. Hanwen Sun, Peiyun Chen, Fei Wang, Haifang Wen,

Investigation on enhanced chemiluminescence reaction

systems with bis(hydrogenperiodato) argentate(III) complex

Ramadan et al.

Int J Pharm Pharm Sci, Vol 4, Suppl 5, 255-261

261

anion for fluoroquinolones synthetic antibiotics, Talanta,

2009;79: 134-140.

13. Li Ming Du, Ya Qin Yang, Qing Mei Wang, Spectrofluorometric

determination of certain quinolone through charge transfer

complex formation. Anal Chimi Acta,2004;516:237-243.

14. Liming D, Qingqin X, Jianmei Y, Fluorescence spectroscopy

determination of fluoroquinolones by charge-transfer reaction.

J Pharm Biomed Anal, 2003; 33:693-698.

15. El-Kommos ME, Saleh GA, El-Gizawi SM, Abou-Elwaf MA,

Spectrofluorometric determination of certain quinolone

antibacterials using metal chelation. Talanta, 2003; 60:1033-

1050.

16. Wei W, Wang H, Jiang C, Spectrofluorimetric determination of

trace heparin using lomefloxacin-terbium probe.

Spectrochimica Acta Part A, 2006; 63:241-246.

17. Zhou Y, Lu Q, Liu C, She S, Wang L, Spectrofluorimetric study on

the inclusion interaction between lomefloxacin and p-

sulfonated calix[4]arene and its analytical application.

Spectrochimica Acta Part A, 2006; 64:748–756.

18. Abd El-Halim HF, Mohamed GG, El-Dessoukya MMI, Mahmoud

WH, Ligational behaviour of lomefloxacin drug towards Cr(III),

Mn(II), Fe(III), Co(II),Ni(II), Cu(II), Zn(II), Th(IV) and UO2(VI)

ions: Synthesis, structural characterization and biological

activity studies. Spectrochimica Acta Part A, 2011; 82: 8– 19.

19. Tong CL, Xiang GH, Sensitive determination of norfloxacin by

the fluorescence probe of terbium (III)-sodium dodecylbenzene

sulfonate and its luminescence mechanism. J Fluoresc,

2006;16:831-837.

20. Tong CL, Xiang GH, Sensitive determination of enoxacin by its

enhancement effect on the fluorescence of terbium(III)–sodium

dodecylbenzene sulfonate and its luminescence mechanism. J

Lumin, 2007; 126:575-580.

21. Ocana JA, Barragan FJ, Callejn M, Fluorescence and terbium-

sensitised luminescence determination of garenoxacin in

human urine and serum. Talanta, 2004; 63:691-697.

22. Ocana JA, Callejon M, Barragan FJ, Determination of

trovafloxacin in human serum by time resolved terbium-

sensitised luminescence. Eur J Pharm Sci, 2001;13:297-301.

23. Vilchez JL, Araujo L, Prieto A, Navalon A, Differential-pulse

adsorptive stripping voltammetric determination of the

antibacterial lomefloxacin, J Pharm Biomed Anal, 2001; 26:23-

29. 24. Abdel Ghani NT, EL-Ries MA, EL-Shall MA, Validated

Polarographic Methods for the Determination of Certain

Antibacterial Drugs. Anal Sci, 2007; 23:1053-1058.

25. Zhang N, Zhang X, Zhao Y, Voltammetric study of the

interaction of lomefloxacin (LMF)–Mg(II) complex with DNA

and its analytical application. Microchemical J, 2003; 75:249-

254. 26. López C, Núñez-Vergara LJ, Squella JA, Alvarez-Lueje A,

Voltammetric behavior and analytical applications of

lomefloxacin, an antibacterial fluorquinolone. J AOAC Int, 2001;

84:649-658.

27. El-Ries MA, Wassei AA, Abdel Ghani NT, El-Shall MA,

Electrochemical adsorptive behavior of some fluoroquinolones

at carbon paste electrode. Anal Sci, 21 (2005) 1249.

28. Shi Qiao-cui1,Wang Su-fen, Electrochemical studies of

lomefloxacin and its interaction with DNA. J Lanzhou University

(Medical Sciences), 2007; 33:46-50.

29. Ibrahim MS., Shehatta IS., Sultan MR., Cathodic adsorptive

stripping voltammetric determination of Nalidixic acid in

pharmaceuticals, human urine and serum, Talanta, 2002;

56:471-479.

30. Corti P, Corbini G, Gratteri P, Furlanetto S, Pinzauti S,

Determination of some Quinolones in tablets, human plasma

and urine by differential-pulse polarography. Int J Pharm,

1994;111:83-87.

31. Jaber AMY, Lounici A, Polarographic behaviour and

determination of Norfloxacin in tablets, Anal Chimi Acta, 1994;

291:53-64.

32. Pandey R et al., Electrochemical behaviour of fourth-generation

fluoroquinolone antibacterial drug moxifloxacin by DC

polarography and cyclic voltammetry. Int J of Pharmacy and

Pharm Sci, 2012; 4:349-355.

33. Abhishek KJ, Chandra PJ, Effect of superdisintegrating agent

and osmogens on ciprofloxacin loaded naturally occurring

biodegradable coated tablets for colon targeting. Int J of

Pharmacy and Pharm Sci, 2010;2:160-165.

34. Ramadan AA, Mandil H,, Determination of gatifloxacin in pure

form and pharmaceutical formulations by differential pulse

polarographic analysis, Analytical Biochemistry, 2010; 404: 1-7.

35. Ramadan AA, Mandil H, Genco T, Determination of

carbinoxamine maleate in pharmaceuticals by direct and

differential pulse polarography, Asian J Chem, 2009;

21(9):7387-7397.

36. Ramadan AA, Mandil H,, Hafez B, Determination of dipyrone in

pure form and pharmaceutical formulations by differential

pulse polarographic analysis, Asian J Chem, 2011; 21(1):403-

406.

37. Ramadan AA, Mandil H, Hafez B, Novel differential pulse

polarographic method For determination of atorvastatin in

pharmaceutical dosage forms using dropping mercury

electrode in borax buffer at pH7.50, Asian J Chem, 2013; 25, In

press.