ScienceAsia 32 (2006): 403-409

doi: 10.2306/scienceasia1513-1874.2006.32.403

Spectrophotometric and Titrimetric Determination

of Ciprofloxacin Based on Reaction
with Cerium (IV) Sulphate
Kanakapura Basavaiah 1*, Paregowda Nagegowda 1, Bankavadi Chikkaswamy
Somashekar1and Veeraiah Ramakrishna2
1
Department of Chemistry, University of Mysore, Manasagangothri, Mysore – 570 006, Karnataka, India.
2
Department of Pharmaceutical Chemistry, Govt. College of Pharmacy, Bangalore-560027, Karnataka.
India.

* Corresponding author, E-mail: [email protected]

Received 24 Aug 2005

Accepted 16 Jun 2006

ABSTRACT: One titrimetric and two spectrophotometric methods are described for the determination of
ciprofloxacin in bulk drug and in formulations using cerium (IV) sulphate as the oxidimetric agent and
methyl orange and indigo carmine as chromogenic agents. In titrimetry (method A), ciprofloxacin is treated
with a measured excess of cerium (IV) sulphate in acid medium and the unreacted oxidant is back titrated
with standard ammonium ferrous sulphate using ferroin indicator. In spectrophotometric methods,
ciprofloxacin is treated with a known excess of cerium (IV) sulphate and the residual oxidant is determined
by treating with a fixed amount of either methyl orange, and measuring the absorbance at 520 nm (Method
B) or indigo carmine, and measuring the absorbance at 610 nm (Method C). In all the three methods, the
amount of cerium (IV) sulphate reacted corresponds to the amount of ciprofloxacin. Titrimetry is applicable
over 2-12 mg range and in the spectrophotometric methods, calibration curves are linear over the
concentration ranges of 0.5-3.5 µg ml-1 (method B) and 1.0-7.0 µg ml-1 (method C). The methods were
satisfactorily applied to the determination of ciprofloxacin in tablet and injection formulations and no
interferences from excipients were noticed.

KEYWORDS: Ciprofloxacin; titrimetry; spectrophotometry; cerium(IV) sulphate; two dyes; dosage forms;
redox reaction.

INTRODUCTION Assay of CPF in pharmaceuticals has previously

been achieved by several analytical techniques such as
Ciprofloxacin (CPF) is, chemically, 1-cyclopropyl- HPLC5-10, HPTLC11, capillary electrophoresis12,13, high
6-fluoro-1,4- dihydro-4- oxo- 7 (piperazin-1-yl) performance capillary electrophoresis14, fluorimetry15
quinoline-3-carboxylic acid (Fig.1) and belongs to the spectrofluorimetry16, chemiluminometry17, ISE-based
group of synthetic fluoroquinolone antibiotics with potentiometry18 and voltammetry19,20. However, many
broad antimicrobial activity1, and is structurally related of these require expensive equipment and skilled
to nalidixic acid. It is believed that the mode of action operation. UV-spectrophotometry has also been used
of this family of drugs is through binding DNA-gyrase for the assay of CPF in single dosage forms9, and in two
enzyme2. It is also reported that there is a direct component mixture21,22.
correlation of fluoroquinolone bonding with inhibition
of DNA-gyrase enzyme activity and induction of DNA
breakage. Because of this special mechanism of action,
fluoroquinolones are considered to be the most N
effective gram-positive-gram-negative pathogens to N
combat infections caused by micro organisms that are N
resistant to other microbials, such as tetracycline. The
drug is official in British Pharmacopoeia3 and United F COOH
States Pharmacopoeia 4 which describe a high O
performance liquid chromatographic (HPLC) method
for its assay. Fig 1. Structure of Ciprofloxacin.
404 ScienceAsia 32 (2006)

Literature survey revealed that only two titrimetric stock solution (0.025 M) was used for titrimetric work
methods have been proposed for the assay of CPF in and diluted appropriately with 1M sulphuric acid to
dosage forms. The acid dye biphasic titration proposed yield 250 & 500 µg ml-1 cerium (IV) sulphate solutions
by Zhang et al23 is performed in aqueous-CHCl3 medium for use in spectrophotometric method B and method
whereas the non aqueous titrimetric procedure24 of C, respectively.
Kilic et al is applicable over 15-50 mg range. Numerous Ferrous ammonium sulphate (0.025M): A 0.025
visible spectrophotometric methods based on redox25, M FAS solution was prepared by dissolving 9.80 g of the
oxidative-coupling26, binary complexation27-28, ternary chemical (Qualigens India Ltd., Mumbai, India) in acid
complexation29, charge-transfer complexation30,31 and and diluting to 1 litre with the water and standardized
ion-pair complexation32-33 reactions are found in the with pure potassium dichromate and the stock solution
literature for the assay of CPF in formulations. However, was used for titrimetric work
most of these methods suffer from such disadvantage Methyl Orange (50 µg ml-1): A 500 µg ml-1 solution
as poor sensitivity25-29, heating30 or extraction step32,33 was first prepared by dissolving 59 mg of dye (S. d. Fine
as shown in Table 1. Chem, Mumbai, India; dye content 85 %) in water and
In this communication, we demonstrate the use of diluting to the mark in a 100 ml calibrated flask and
titrimetric and spectrophotometric techniques for the filtered. This was diluted 10-fold to obtain a working
assay of CPF using cerium (IV) sulphate. concentration of 50 µg ml-1.
Indigo carmine (200 µg ml-1): A 1000 µg ml-1
MATERIALS AND METHODS solution was first prepared by dissolving 111 mg of dye
(S. d. Fine Chem., Mumbai, India; dye content 90 %) in
Apparatus water and diluting to the mark in a 100 ml calibrated
All absorbance measurements were made with a flask and filtered. This was appropriately diluted to get
Systronics Model 106 digital spectrophotometer 200 µg ml-1 solution with water.
provided with matched 1-cm quartz cells. Sulphuric acid (5 M): A 272 ml of concentrated
sulphuric acid (S. d. Fine Chem, Mumbai, India; Sp gr
Reagents and Solutions 1.84) was added to 728 ml water with cooling.
All chemicals used were of analytical reagent grade Ferroin indicator: A 0.07 g of iron (II) sulphate
and distilled water was used to prepare all solutions. heptahydrate and 0.15 g of 1,10-phenanthroline
Cerium (IV) Sulphate (0.025M): A 0.025 M hydrate were dissolved in 10 ml of distilled water.
cerium (IV) sulphate solution was prepared by
dissolving about 10 g of the chemical (Loba-Chemie Standard Ciprofloxain Solution
Indoaustranal Co., India) in 1.0 M sulphuric acid and A stock standard solution containing 2 mg ml-1 CPF
diluting to 1 litre with the same acid and standardized was prepared by dissolving 500 mg of pure sample
with a solution of ammonium ferrous sulphate. The (Torrent Pharmaceuticals, Ahmedabad, India) in water

Table 1. Comparision of the existing spectrophotometric methods with the proposed methods.

Sl Reagent/s λmax,nm Linear range ( µg ml-1) Remarks Ref.

No used* ε (l mol-1 cm-1)

1 Cerium (IV) sulphate 345 12-120 (5.1x 103) Involves extraction into CHCl 3 25
2 Iron (III) - MBTH 425 6-12 30 min contact time, less stable colour, 26
expensive reagent
3 Iron (III) chloride 432 50-125 Less sensitive 27
4 Iron (III) 447 50-500 Uses flow injection automated assembly, 28
less sensitive
5 Iron (III) nitrate 375 35-300 Less sensitive 29
6 TCBQ 376 0.9-25 (1.27x104) Involves heating at 35ÚC for 30 min 30
7 p-benzoquinone 495 Involves rigid pH control 31
8 a)Bromocresol Purple 410 1.5-16.5 (1.7x10 4) Involves rigid pH control and 32
b) Bromophenol Blue 410 1.5-12.0 (1.6x104) liquid - liquid extraction
9 Supracene Violet 3B 575 2.5-30 (8.62x10 3) Involves rigid pH control and 33
liquid - liquid extraction
10 a. Ce (IV) sulphate-MO 520 0.5-3.5 (6.1 x 104) Non-stringent working conditions, Present
b. Ce (IV) sulphate - IC 610 1.0 -7.0 (3.0 x 104) no heating or no extraction step, methods
highly sensitive

* MBTH, 3-methyl-2-bezothioazolin-2-one-hydrazone; TCBQ, Tetrachlorobenzoquinone; MO, Methyl orange; IC, Indigo carmine.
ScienceAsia 32 (2006) 405

and diluting to the mark in a 250 ml calibrated flask, Whatman No. 42 filter paper. First 10 ml portion of the
and used in titrimetric work. This solution (2000 µg ml-1 filtrate was discarded and a suitable aliquot was
CPF) was diluted stepwise with water to obtain working subjected to analysis by titrimetry. The tablet extract
concentrations of 10 and 20 µg ml-1 for investigations (2000 µg ml-1) was suitably diluted to get 10 and 20 µg
by spectrophotometric method B and method C, ml-1 CPF and analysed spectrophotometrically by
respectively. taking a convenient aliquot.

General Procedures RESULTS AND DISCUSSION

Titrimetry (Method A) A): A 10-ml aliquot of standard
drug solution containing 2-12 mg of CPF was placed in The proposed methods are indirect and are based
a 100-ml titration flask and the solution was acidified on the determination of the residual cerium (IV)
by adding 5 ml of 5 M sulphuric acid. Then, 10 ml of sulphate after the reaction between CPF and the oxidant
0.025 M cerium (IV) sulphate solution was added by is ensured to be complete in acid medium. The amount
means of a pipette, the contents mixed well and the of oxidant reacted corresponds to the amount of drug
flask set aside for 15 min. Finally, the unreacted oxidant in all the methods.
was back titrated with 0.025 M FAS solution using one Titrimetry: Direct titration of CPF with cerium (IV)
drop of ferroin indicator. Simultaneously, a blank sulphate was not successful. Hence, several
titration was performed, and the amount of drug in the experimental variables were optimized for the indirect
measured aliquot was calculated from the amount of determination. Reproducible and stoichiometric results
cerium(IV) reacted. were obtained when 0.2-2.0 M sulphuric acid
Spectrophotometric method B (Methyl orange): concentration was maintained, and hence a 1.0 M acid
Different aliquots (0.5-3.5 ml) of a standard 10 µg ml-1 concentration was used throughout (Fig.2). The
CPF solution were transferred into a series of 10 ml
calibrated flasks by means of a micro burette and the 7.25
total volume was adjusted to 4.0 ml by adding water. To 7.2
each flasks were added 1 ml each of 5 M sulphuric acid 7.15
and 250 µg ml-1 cerium (IV) sulphate solutions, mixed 7.1
well and the flasks were kept aside for 10 min with 7.05
occasional swirling. Then, 1 ml of methyl orange solution
n

7
was added and the volume was diluted to the mark with 6.95
water and mixed. The absorbance of each solution was 6.9
measured at 520 nm against a water blank after 5 min. 6.85
Spectrophotometric method C (Indigo carmine): 6.8
Varying aliquots (0.5-3.5 ml) of a standard 20 µg ml-1 0 0.5 1 1.5 2 2.5
CPF solution were accurately measured into a series of H2SO4 concentration, M.

10 ml calibrated flasks and the volume was adjusted to Fig 2. Effect of H2SO4 concentration.
4.0 ml by adding requisite quantity of water. To each
flask were added 1 ml of 5 M sulphuric acid followed
by 1 ml of 500 µg ml-1 cerium (IV) sulphate solutions. reaction was found to be quantitative with a
The contents were mixed well and the flasks set-aside stoichiometry of 1:7 (CPF: oxidant) for the range
for 10 min. Then, 1 ml of indigo carmine solution was studied (2-12 mg). The reaction was found to be
added, the volume was diluted to the mark with water, complete in 15 minutes yielding a stoichiometry of 1:7.
and mixed well. The absorbance of each solution was Contact times beyond 15 minutes and up to 40 minutes
measured at 610 nm against a water blank after 5 min. consumed a small amount of oxidant, but without
The concentration of the unknown was read from yielding any significant stoichiometry (Fig.3). Hence it
the calibration graph or computed from the respective is necessary that the oxidation reaction be terminated
regression equation. after 15 minutes.
Since seven moles of oxidant are consumed by each
Procedure for Formulations mole of CPF, the reaction path way is unclear. However,
Twenty tablets were weighed and ground into a additional study will be performed to reveal the reaction
fine powder. An amount of powder equivalent to 500 mechanism.
mg of CPF was accurately weighed into a 250 ml Spectrophotometric methods: The ability of
calibrated flask, 60 ml of water added and the mixture cerium (IV) sulphate to cause oxidation of CPF and
shaken for 20 min. Then, the volume was made up to bleach the colour of methyl orange and indigo carmine
the mark with water, mixed well and filtered using a dyes has been used for the indirect spectrophotometric
 406 ScienceAsia 32 (2006)

7.25
Preliminary experiments were performed to fix the
7.2
maximum concentrations of the dyes that could be
7.15
7.1
determined spectrophotometrically, and these were
7.05 found to be 5 and 20 µg ml-1 for methyl orange and
n

7 indigo carmine, respectively. A cerium (IV) sulphate

6.95 concentration of 25.0 µg ml-1 was found to destroy the
6.9 red colour due to 5 µg ml-1 methyl orange whereas in
6.85
the case of 20 µg ml-1 indigo carmine, 50.0 µg ml-1
0 10 20 30 40 50
Reaction time, min.
cerium (IV) sulphate was sufficient to bleach the blue
Fig 3. Effect of reaction time. colour in acid conditions. Hence, different amounts of
CPF were reacted with 1.0 ml of 250 µg ml-1 oxidant in
assay of CPF. In both methods, the drug was reacted method B and 1.0 ml of 500 µg ml-1 oxidant in method
with a measured excess of cerium (IV) sulphate in acid C before determining the residual cerium (IV) sulphate
medium and the unreacted oxidant was determined by as described under the respective procedures.
reacting with either methyl orange or indigo carmine The reaction was carried out in sulphuric acid
followed by absorbance measurement at 520 or 610 medium. One ml of 5 M acid was used in the assay
nm. In either method, the absorbance increased linearly procedures. For quantitative reaction between CPF
with increasing concentration. and cerium (IV) sulphate a contact time of 10 min was
CPF, when added in increasing amounts to a fixed found sufficient in both methods and constant
amount of cerium (IV) sulphate, consumed the latter absorbance readings were obtained when contact times
and there occurred a concomitant fall in its were extended upto 30 min. The standing time of 5 min
concentration. When fixed amount of either dye was was necessary for the bleaching of dye colour by the
added to decreasing amounts of oxidant, a concomitant residual oxidant. The measured colour was stable for
increase in the concentration of dye resulted. This was hours in the presence of reaction product.
observed as a proportional increase in absorbance at
the respective λmax with increasing concentration of Analytical Parameters of the Spectrophotometric
CPF (Fig. 4 and 5). Methods
A linear relation was found between absorbance at
0.7
λmax and concentration of CPF in the ranges shown in
0.6 Table 2. The calibration graphs are described by the
0.5 equation:
Absorbance

0.4
Y=a+bX
(where Y = absorbance, a = intercept, b = slope and
0.3
X = concentration in µg ml-1) obtained by the method
0.2 of least squares. The apparent molar absorptivity and
0.1 Sandell sensitivity values together with the limits of
0
detection and quantification compiled in Table 2 are
indicative of the high sensitivity of the proposed
0 1 2 3 4 5
methods.
Concentration of drug,µg ml-1
Fig 4. Beer’s law curve for method B.
Table 2. Analytical parameters for spectrophotometric
0.7 methods.
0.6
Parameter Method B Method C
0.5
Absorbance

λmax, nm 520 610

0.4 Beer’s law limits, µg ml-1 0.5-3.5 1.0-7.0
0.3 Molar absorptivity, l mol-1 cm-1 6.1 × 104 3.0 × 104
Sandell sensitivity, µg cm-2 0.005 0.011
0.2 Limit of detection, µg ml-1 0.05 0.09
Limit of quantification, µg ml-1 0.16 0.31
0.1 Regression equation, Y*
0 Intercept (a) 8.6 × 10-3 1.8 × 10 -3
Slope (b) 0.18 0.09
0 1 2 3 4 5 Correlation coefficient (r) 0.9971 0.9897
Concentration of drug, µg ml-1
Fig 5. Beer’s law curve for method C. *Y= a + b X where Y is the absorbance, a intercept, b slope and X concentration in µg ml-1.
ScienceAsia 32 (2006) 407

Table 3. Evaluation of accuracy and precision.

Method* CPF Taken

Taken CPF Found Range Relative er
errror
or,, % SD RSD, %

Titrimetry (method A) 4 4.09 0.36 2.25 0.03 0.77

8 7.90 0.30 1.13 0.08 1.02
12 11.8 0.34 1.67 0.20 1.74
Spectrophotometric method B 1.0 0.98 0.17 2.00 0.02 2.33
2.0 2.04 0.16 2.00 0.01 0.57
3.0 2.98 0.19 0.66 0.04 1.46
Spectrophotometric method C 2.0 2.03 0.25 1.50 0.02 0.86
5.0 4.96 0.29 0.80 0.10 2.12
7.0 6.92 0.30 1.14 0.09 1.38

* In method A, CPF taken/found, range and SD are in mg while in methods B and C, the same are in µg ml-1.
SD, standard deviation; RSD, relative standard deviation.

Method V alidation
Validation 98.68-103.72 (Table 4) revealing good accuracies and
Accuracy and Precision non-interference from excipients and diluents such as
The accuracy and precision of the methods were talc, starch, gelatin, gum acacia, calcium carbonate, calcium
evaluated by performing seven replicate analyses on gluconate, calcium dihydrogen orthophosphate, sodium
pure drug solutions at three different amount/ alginate and magnesium stearate. This was further
concentration levels (within the working ranges). The confirmed by the fact that no more than the
relative error (%), an indicator of accuracy was within stoichiometric amount of cerium (IV) was consumed
2.5% and intra day precision which is also called the when the tablet extract/injection solution was treated
repeatability expressed in relative standard deviation with cerium (IV) under the described experimental
(RSD) (%) was also less than 2.5%, indicating the high conditions.
accuracy and precision of the methods. The results of
this study are compiled in Table 3. The reproducibility Application
of the methods, also called the day-to-day precision, Commercial tablets and injections containing CPF
was assessed by performing replicate analyses on pure were successfully analysed by the proposed methods.
drug solutions at three levels over a period of five days Co-formulated substances did not interfere. For the
preparing all solutions afresh each day. The day-to-day purpose of comparison, the same batch tablets and
RSD values were less than 4% reflecting the usefulness injections were analysed by an established method9.
of the methods in routine use. The results of the assay are presented in Table 5. As
The accuracy and precision of the methods were shown in Table 4, the results of analysis obtained by the
further assessed by performing recovery experiments. proposed methods are in conformity with those
To a fixed amount of drug in the dosage form (pre- obtained by the reference method9. The performance
analyzed) pure drug was added at three different levels of the methods was further ascertained by applying
and the total was found by the proposed methods. Student’s t-test for accuracy and F-test for precision. At
Each test was performed in triplicate. The percent the 95% confidence level, the calculated t- and F-values
recoveries of the added pure CPF were in the range of did not exceed the tabulated values (t = 2.77 and F =

Table 4. Results of analysis of dosage forms containing CPF.

Brand nameψ Label claim, % found* ± SD

and dosage form mg/tablet or mg/ml Reference method Method A Method B Method C

Ciproleta tablets 100 99.36 ± 0.74 100.36 ± 0.86, 99.84 ± 1.26, 101.72 ±1.55,
t = 1.77, F = 2.35 t = 1.09,F = 2.90 t = 2.27,F = 4.38
Quintor b tablets 250 101.72 ±1.26 100.3 ± 1.82, 99.3 ± 1.28, 99.61 ± 1.13,
t = 1.52,F = 2.08 t = 2.18,F = 1.03 t = 2.10,F = 0.80
Quintor b injections 2 100.28 ±0.91 98.67 ± 1.16, 99.97 ± 1.64, 101.34± 1.45,
t = 0.79,F =1.62 t =0.78, F = 3.25 t = 1.50,F = 2.53

* Mean value of five determinations.

ψ
Marketed by: a. Dr. Reddy’s Laboratories.
b. Torrent pharmaceuticals.
Tabulated t-value at 95% confidence level is 2.77.
Tabulated F-value at 95% confidence level is 6.39.
408 ScienceAsia 32 (2006)

Table 5. Results of recovery study by standard-addition method.

Formulation Titrimetry (method A) Spectrophotometry (Method B) Spectrophotometry (Method C)

studied Amount of Amount Total % Amount of Amount Total, % Amount of Amount Total %
CPF in of pure found, recovery CPF in of pure found recovery CPF in of pure found, recovery
formulation, CPF mg of pure formulation, CPF µ g of pure formulation, CPF µ g of pure
mg added, mg CPF * µg added, µg CPF * µg added, µg CPF *

Ciprolet 4.02 2.0 6.05 101.3 10.03 5.0 14.96 98.50 20.3 10 30.45 101.5
tablet 4.02 4.0 7.97 98.68 10.03 10.0 19.79 97.60 20.3 20 40.07 98.84
(100 mg) 4.02 6.0 9.97 99.14 10.03 20.0 30.51 102.40 20.3 40 60.42 100.3

Quintor 3.95 2.0 5.91 98.15 9.87 5.0 15.02 103.1 20.27 10 30.74 104.72
Injections 3.95 4.0 8.01 101.4 9.87 10.0 19.92 100.5 20.27 20 40.20 99.66
(2 mg ml-1) 3.95 6.0 9.94 99.78 9.87 20.0 29.49 98.10 20.27 40 60.95 101.70

*Mean value of three determinations.

6.39) suggesting that the proposed methods are as REFERENCES

accurate and precise as the established/reference
method. 1. Goodman LS and Gillman AG (1996) The Pharmacological
Basis of Therapeutics, 9 th ed (McGraw-Hill, NewYork) pp
1065.
CONCLUSIONS 2. Wise R, Andrews JM and Edwards LJ (1983) Antimicrob
Agents Chemother 23, 559.
Three new methods using cerium (IV) sulphate as 3. The British Pharmacopoeia (1999) Vol 2 (Her Majesty’s
the oxidimetric reagent have been developed for the Stationery Office, London) pp 1714.
4. The United States Pharmacopoeia 24 (1999) (United States
determination of ciprofloxacin based on oxidation. Pharmacopoeial Convention, 12601, Twinbrook Parkway,
The titrimetric method, although has a narrow dynamic Rockville, MD 20852) pp 420.
range of applicability, offers a better sensitivity 5. Zatou A and Miltiadou N (2002) Sensitive LC-determination
compared to the methods reported previously. The of ciprofloxacin in pharmaceutical preparations and
present spectrophotometric methods using cerium (IV) biological fluids with fluorescence detection, J Pharm Biomed
Anal 28, 559-68.
sulphate have long dynamic linear ranges of response 6. Vega E. Dabbane V, Nassetta M and Sola N (1999) Validation
and better sensitivity in terms of molar absorptivities of reversed phase LC method for quantitative analysis of
and limits of detection and are free from boiling step intravenous admixtures of ciprofloxacin and metronidazole,
compared to many of the previously reported J Pharm Biomed Anal 21, 1003-9.
procedures. The methods involve the measurement of 7. Lacriox PM, Curran NM and Sears RW (1996) High pressure
liquid chromatographic methods for ciprofloxacin
stable coloured species, have shorter contact times hydrochloride and related compounds in raw materials, J
and are free from extraction step. The other advantages Pharam Biomed Anal 14, 641-54.
include the use of cerium (IV) which is highly stable in 8. Husain S, Khalid S, Nagaraju V and Nageshwara Rao R (1995)
solution. These advantages coupled with fairly high High performance liquid chromatographic separation and
accuracy and precision of the methods render them determination of small amounts of process impurities of
ciprofloxacin in bulk drugs and formulations, J Chromatogr
suitable for routine use. However, the reaction time in A 705
705, 380-4.
titrimetry is some what critical and should be strictly 9. Liu RL, Xu JR, Liu YG and Yao Z (1994) Studies on methods
adhered to. for determination of ciprofloxacin hydrochloride, Yaowu
Fenxi Zazhi 14, 45-6.
ACKNOWLEDGEMENTS 10. Morley JA and Elrod L (1993) Determination of
fluoroquinolone antibacterials as N-acyl derivatives,
Chromatographia 37, 295-9.
The authors gratefully acknowledge the receipt of 11. Novakovic J, Nesmerak K, Nova H and Filka K (2001) An
pure ciprofloxacin as gift from Torrent Pharmaceuticals HPTLC method for the determination and the purity control
Ltd, Ahmedbad, India. The authors (PN, BCS&VRK) of ciprofloxacin HCl in coated tablets, J Pharm Biomed Anal
thank the authorities of the University of Mysore, 25, 957-64.
12. Wang PL, Feng YL and Chen LA (1997) Validation of capillary
Mysore, for research facilities. One of the author (VRK)
electrophoresis method for the determination of quinolone
is thankful to the Principle Secretary, Dept of Health antibiotic and its related impurities, Microchem J 56, 229-
and Family Welfare, Govt of Karnataka, Bangalore, for 35.
permission. 13. Altria KD and Chanter YC (1993) Validation of a capillary
ScienceAsia 32 (2006) 409

electrophoresis method for the determination of a quinolone 32. Tosunoglu S and Savci N (1993) Two spectrophotometric
antibiotic and its related impurities, J Chromatogr A 652, methods for the determination of ciprofloxacin in
459-63. pharmaceuticals with use of bromocresol purple and
14. Yin C and Wu YT (1997) Determination of four quinolones bromophenol blue, Acta Pharm Turc 35, 1-5.
by high performance capillary electrophoresis, Yaowu Fenxi 33. Sastry CSP, Rama Rao K and Prasad DS (2003) Extractive
Zazhi 17, 371-3. spectrophotometric determination of some fluoroquinoline
15. Zhou CJ, Liu N and Guo YE (1998) Fluorimetric derivatives in pure and dosage forms, Talanta 42, 311-6.
determination of the content of ciprofloxacin hydrochloride
ointments, Yaowu Fenxi Zazhi 18, 200-1.
16. Drakopoulos AI and Ionnou PC (1997) Spectrofluorimetric
study of acid-base equilibria and complexation behaviour
of the fluroquinone antibiotic ofloxacin, norfloxacin,
ciprofloxacin and pefloxacin in aqueous solutions, Anal Chim
Acta 354, 197-204.
17. Liang YD, Li JZ and Zhang Z J (1997) Flow injection
chemiluminescence determination of ciprofloxacin
hydrochloride, Fenxi Huaxe 25, 1307-10.
18. Avsec H and Gomiscek S (1992) Study of the prospects for
a ciprofloxacin PVC-coated wire ion-selective electrode on
quinolin-4-ones, Anal Chim Acta 268, 307-9.
19. Di JW and Jin M (1995) Study on the determination and
electrode mechanism of ciprofloxacin by LSP, Fenxi Shiyanshi
14, 33-6.
20. Chen Y, Han FM and Yuan ZB (1995) Single sweep
polarographic analysis of ciprofloxacin, Fenxi Kexue Xuebao
11, 55-7.
21. Zhang LT, Yuan ZF, Chen RH, Zhou ZX, Zhou YM, Zhang
AH, Liu WN and Whang ZH (1997) Determination of
ciprofloxacin hydrochloride in tablets by differential
spectrophotometry, Yaowu Fenxi Zazhi 17, 33-4.
22. Bungalowala A, Jain DK and Trivedi P (1998) Simultaneous
determination of ciprofloxacin and tinidazole in tablet dosage
forms, Indian Drugs 35, 348-51.
23. Zhang SF, Sun ZX and Sun XL (1996) Determination of
ciprofloxacin lactate in injections by acid dye biphasic
titration, Yaowu Fenxi Zazhi 16, 402.
24. Kilic E, Koseoglu F and Akay M (1994) A Non-aqueous
titrimetric assay of selected antibiotics using
tetrabutylammonium hydroxide as titrant, J Pharm Biomed
Anal 12, 347-52.
25. Bharat PV, Rajani G and Vanita S (1997) An oxidative
spectrophotometric method for the determination of
ciprofloxacin in pharmaceutical preparations, Indian Drugs
34, 497-500.
26. Ramana Rao G, Avadhanulu AB and Vasta DK (1990)
Spectrophotometric determination of ciprofloxacin in its
dosage forms, Indian Drugs 27, 532-5.
27. Bhowal SK and Das TK (1990) Spectrophotometric
determination of some recently introduced antibacterial
drugs using ferric chloride, Anal Lett 24, 25-37.
28. Sultan SM and Suliman F O (1992) Flow-injection
spectrophotometric determination of the antibiotic
ciprofloxacin in drug formulations, Analyst (London) 117,
1523-6.
29. Chowdary KPR and Rama Prasad YV (1994)
Spectrophotometric estimation of ciprofloxacin
hydrochloride in dosage forms and in dissolution rate
studies, Indian Drugs 43, 277-9.
30. Xuan CS, Ren SC, Song JL and Wang ZY (1996)
Spectrophotometric determination of ciprofloxacin using
tetrachlorobenzoquinone, Yaowu Fenxi Zazhi 16, 164-6.
31. Shanbag SG, Thampi PP and Thampi CS (1990) Simple
spectrophotometric method for the estimation of
ciprofloxacin hydrochloride and its dosage forms, Indian
Drugs 28, 279-80.