Journal of Analytical Methods in Chemistry

Journal of Analytical Methods in Chemistry / 2018 / Article

Research Article | Open Access

Volume 2018 |Article ID 8436948 | 11 pages |

Determination of Fluoroquinolones in Pharmaceutical Formulations by Extractive Spectrophotometric Methods Using Ion-Pair Complex Formation with Bromothymol Blue

Academic Editor: Bengi Uslu
Received11 Mar 2018
Revised16 Jun 2018
Accepted01 Aug 2018
Published04 Oct 2018


In this paper, we reported a new, simple, accurate, and precise extractive spectrophotometric method for the determination of fluoroquinolones (FQs) including ciprofloxacin (CFX), levofloxacin (LFX), and ofloxacin (OFX) in pharmaceutical formulations. The proposed method is based on the ion-pair formation complexes between FQs and an anionic dye, bromothymol blue (BTB), in acidic medium. The yellow-colored complexes which were extracted into chloroform were measured at the wavelengths of 420, 415, and 418 nm for CFX, LFX, and OFX, respectively. Some effective conditions such as pH, dye concentration, shaking time, and organic solvents were also systematically studied. Very good limit of detection (LOD) of 0.084 µg/mL, 0.101 µg/mL, and 0.105 µg/mL were found for CFX, LFX, and OFX, respectively. The stoichiometry of the complexes formed between FQs and BTB determined by Job’s method of continuous variation was 1 : 1. No interference was observed from common excipients occurred in pharmaceutical formulations. The proposed method has been successfully applied to determine the FQs in some pharmaceutical products. A good agreement between extractive spectrophotometric method with high-performance liquid chromatography mass spectrometry (HPLC-MS) for the determination of FQs in some real samples demonstrates that the proposed method is suitable to quantify FQs in pharmaceutical formulations.

1. Introduction

Fluoroquinolones (FQs) are the important antibiotics used for the treatment of Gram-negative bacterial infections in both human and veterinary medicine. They are derivatives of 4-quinolone, which have unsubstituted or substituted piperazine ring attached at the 7-position to the central ring system of quinoline as well as fluorine atom at the 6-position. The FQs are useful to treat a variety of infections, including soft-tissue infections, respiratory infections, urinary tract infections, bone-joint infections, typhoid fever, prostatitis, sexually transmitted diseases, acute bronchitis, community-acquired pneumonia, and sinusitis [13].

Ciprofloxacin (CFX), which is one of the second-generated groups of synthetic FQs, can exhibit greater intrinsic antibacterial activity and make a broader antibacterial spectrum. Ofloxacin (OFX) is a chiral compound that is widely used to treat above infections. Levofloxacin (LFX) is the pure (–)-(S)-enantiomer of the racemic drug substance ofloxacin. Figures 1(a)1(c) show the chemical structures of CFX, LFX, and OFX, respectively.

Several techniques like voltammetry [4], flow injection electrogenerated chemiluminescence [5], spectrofluorometry [6, 7], spectrophotometry [8, 9], high-performance liquid chromatography [10, 11], and liquid chromatography tandem mass spectrometry [12, 13] have been used for the determination of fluoroquinolones in pharmaceutical and biological products. Among them, spectrophotometric method has several advantages such as simplicity, fast, and low cost. Spectrophotometry was successfully used for pharmaceutical analysis, involving quality control of commercialized product and pharmacodynamic studies. Spectrophotometric methods for the determination of fluoroquinolones could be classified according to the different reactions: (i) charge-transfer complexation based on the reaction of FQs as electron donors with p-acceptors such as 2,3-dichloro-5,6-dicyano-q-benzoquinone, 7,7,8,8-tetracyanoquinodimethane, q-chloranil, q-nitrophenol, and tetracyanoethylene [7, 1416]; (ii) oxidative coupling reaction using oxidative coupling with 3-methyl-2-benzothiazolinonehydrazone hydrochloride and cerium (IV) ammonium sulfate, Fe(III)-MBTH, tris(o-phenanthroline) iron(II), and tris (bipyridyl) iron(II) [17, 18]; (iii) ion-pair complex formation with acid-dye reagents such as Sudan III, methyl orange, supracene violet 3B, tropaeolin 000, bromophenol blue, bromothymol blue, bromocresol green, and bromocresol purple [8, 14, 19, 20]. These methods were related with some major drawbacks such as having narrow linearity range, requiring heating and close pH control, long time for the reaction to complete, and low stability of the colored product formed.

Bromothymol blue (BTB) (Figure 1(d)) is an anionic dye and that can be protonated or deprotonated to form yellow or blue, respectively. The BTB was used to make ion-pair complex, which was applied to determine many pharmaceutical compounds by extractive spectrophotometric methods [2130]. However, the ion-pair complex between BTB and FQs has not been studied. The method based on ion-pair complexes between analytes and BTB into a suitable organic solvent is also simple, fast, and cheap.

In the previous study, we used sulphonphthalein acid including bromophenol blue, bromocresol green, and bromothymol blue to determine ciprofloxacin pharmaceutical formulations and achieved good results [31].

In this paper, for the first time, we investigated extractive spectrophotometric method based on the formation of ion-pair complexes between ciprofloxacin, levofloxacin, and ofloxacin with BTB subsequent extraction into chloroform. Some effective conditions on the formation of complexes such as pH, shaking time, organic solvent, and the concentration of dye were systematically studied. The present method was also applied to determine FQs in some pharmaceutical formulations including tablets and infusions.

2. Experimental

2.1. Apparatus

A double beam UV-visible spectrophotometer (SP-60, Biochrom Ltd., UK) with 1.0 cm of path length quartz cells was used to measure all sample absorbances. Inolab pH-meter instrument (Germany) was used to monitor the pH of solutions. Three standard buffers were used to calibrate the electrode before measuring pH of solutions. All measurements were conducted at 25  2°C controlled by air conditional laboratory.

2.2. Materials and Reagents

All chemicals used were of analytical grade and double-distilled water was used to prepare all solutions in the present study.

FQs were purchased from Sigma (Germany, with purity >99.0%), whereas bromothymol blue (BTB) was supplied by Maya-R, China, with purity >99%. The organic solvents including chloroform, dichloromethane, carbon tetrachloride, dichloroethane, benzene, toluene, and other chemicals are analytical reagents (Merck, Germany).

The following dosage forms containing FQs were purchased from local pharmacy market and employed in the study: Hasancip and Kacipro tablets equivalent to 500 mg ciprofloxacin (Hasan-Dermapharm and Dong Nam manufacturing-Trading pharmaceutical Co., Ltd, Vietnam). Ciprofloxacin infusion equivalent to 200 mg ciprofloxacin/100 ml solution for infusion (Hebei Tiancheng Pharmaceutical Co., Ltd and Shandong Hualu Pharmaceutical Co., Ltd, China). Stada and DHG tablets equivalent to 500 mg levofloxacin (Stada-VN J.V.Company and DHG pharmaceutical joint–stock company, Vietnam). Ofloxacin (200 mg/tablet) was provided by the Mekophar Chemical Pharmaceutical Company (Vietnam).

2.3. Solution Preparation

A stock solution of FQs (1 mg/mL) in double-distilled water. The working standard solution of FQs containing 100 µg/mL was prepared by appropriate dilution. The stock solution of BTB (0.025%) was prepared in double-distilled water. All stock solutions were kept in dark bottle, stored in 4°C and could be used within one week.

2.4. Construction of Calibration Curves

A series of 125 mL separating funnel, the volumes of working solutions of the drugs in different concentration ranges (CFX (1–35 µg/mL), LFX (0.5–25 µg/mL), and OFX (0.5–25 µg/mL) were transferred. Then, 4.0 mL of 0.025% BTB solution was added before thoroughly mixing. After that, a 10 mL of chloroform was added to each of the separating funnel. The contents were shaken for 2 min and allowed to separate the two layers. The yellow-colored chloroform layer containing the ion-pair complexes was measured at 420 nm for CFX, 415 nm for LFX, and 418 nm for OFX against the reagent blanks. At each concentration, the experiment was repeated 6 times. The colored chromogen complexes are stable for 24 h.

2.5. Sample Preparation

Weigh and mix the contents of twenty tablets of each drug (CFX, LFX, and OFX), an accurately weighed amount of powder equivalent to 0.1 g of drugs transferred into a 100-mL beaker. A magnetic stirrer was used to completely disintegrate the powder in doubly distilled water. Then, filter through a Whatman paper (No 40) and fill up to 100 mL with doubly distilled water in a volumetric flask. The working solution of the drugs containing 100 µg/mL was prepared by dilution and determined under optimum conditions.

2.6. Validation with High-Performance Liquid Chromatography-Mass Spectrometry (HPLC-MS)

Some real samples of three FQs were determined by HPLC-MS using HPLC 20 AXL (Shimadzu, Japan) coupled with electrospray ionisation tandem mass spectrometric detection, ABI 5500 QQQ (Applied BioSystem). The chromatographic conditions are including column C18 MRC-ODS (150 mm × 2.1 mm × 3.5 µm), mobile phase containing acetonitrile (ACN) with formic acid (0.1%) in water under a flow rate of 0.5 ml/min, and gradient elution. The inject volume is 10 µL.

3. Results and Discussion

3.1. Optimum Reaction Conditions
3.1.1. Effect of Extracting Solvent

Six organic solvents including chloroform, carbon tetrachloride, dichloromethane, dichloroethane, benzene, and toluene were used to study the effect of solvent to ion-pair formation between FQs and BTB. Figure 2 shows that chloroform is the most suitable solvent for the extraction of three FQs with low blank absorbance, highest absorbances, and lowest standard deviations. It implies that chloroform is the best extracting solvent to achieve a good recovery of the complexes with the shortest time to reach the equilibrium processes.

3.1.2. Effect of pH

The pH of solution plays an important role in the complex formations. The effect of pH on the formation of ion pairs was examined by varying the pH from 2.0 to 6.0 by adjusting 1 M HCl and 1 M NaOH. The maximum absorbances were observed at pH 3.3, 3.4, and 3.5 for the complexes of BTB and OFX, CFX, and LFX, respectively (Figure 3). These pH values correspond to the initial pH of the examined drug and the dye. Therefore, it is not necessary to adjust the pH before extraction.

3.1.3. Effect of Dye Concentration

The effect of dye concentrations was studied by adding different volumes of 0.025% BTB from 1.0 to 6.0 mL with a fixed concentration of FQs (10 μg/mL) (Figure 4). Figure 4 shows that the maximum absorbance of the complex was achieved with 4.0 mL of 0.025% of BTB in each case and excess dye did not affect the absorbance of the complex. Therefore, 4.0 mL of 0.025% of BTB is optimum dye volume and it is kept as constant for further studies.

3.1.4. Effect of Shaking Time

The effect of shaking time on the formation and stability of the ion-pair complex was investigated by measuring the absorbance of the extracted ion associates with increasing time from 0 to 4.0 min. Figure 5 shows that the ion-pair complexes were formed instantaneously with 2.0 min shaking time. Thus, 2.0 min is the optimum shaking time and it is fixed for further studies.

3.1.5. Stoichiometry of Ion-Pair Complexes

Job’s method of continuous variation of equimolar solutions was employed to evaluate stoichiometry of the complex. A 3.0 × 10−4 M standard solution of three FQs and 3.0 × 10−4 M solution of BTB were used. A series of the solutions were prepared in which the total volume of drug and reagent was kept in 10 mL, whereas the absorbances were measured at 420, 415, and 418 nm, for CFX, LFX, and OFX, respectively. The absorbances were plotted against the mole fraction of the drugs. The stoichiometry for each drug-dye ion-pair complex was found to be 1 : 1 (Figure 6).

3.1.6. Mechanism of Reaction and Absorption Spectra

Fluoroquinolones can contain a secondary amino group (CFX) and a tertiary amino group (LFX and OFX) that can be easily protonated under acidic conditions. On the one hand, the sulphonic acid group in BTB, that is, the only group undergoing dissociation in the pH range 1–5. The colour of BTB is on the basis of lactoid ring and subsequent formation of quinoid group. It is suggested that the two tautomers are plausible in equilibrium due to strong acidic nature of the sulphonic acid group. Thus, the quinoid body must predominate. Finally, the protonated fluoroquinolones form ion pairs with BTB dye that could be quantitatively extracted into chloroform. The possible reaction mechanisms are proposed and given in a scheme in Figure 7.

The absorption spectra of the ion-pair complexes, which were formed between FQs and BTB, were measured in the wavelength range 350–500 nm against the blank solution and shown in Figure 8.

Figure 8 shows that absorption maxima for CFX-BTB, LFX-BTB, and OFX-BTB in chloroform were observed at 420, 415, and 418 nm, respectively. The reagent blanks under similar conditions have insignificant absorbances. At wavelengths 420, 415, and 418 nm, absorption spectrum of BTB does not affect the absorption spectrum of ion-associate complexes of FQs. Therefore, the selectivity of the proposed method for the determination of FQs is guaranteed.

3.1.7. Association Constants of Ion-Pair Complexes

The equation of association constant of ion-pair complex iswhere and are the observed absorbance and the maximum absorbance value when all the drug present is associated, respectively. is the molar concentration of the drugs at the maximum absorbance and n is the stoichiometry in which BTB ion associates with drugs. The conditional stability constants (Kf) of the ion-pair complexes according to Britton [32] for the cases of FQs were calculated from the continuous variation data using the following equation:The conditional stability constants () of the ion-pair complexes for FQs are indicated in Table 1.

SampleVdrug (mL)VBTB (mL)AnnnKflog KfMean




—, not determined.

Table 1 shows that the log Kf values of ion-pair associates for OFX-BTB, LFX-BTB, and CFX-BTB were 6.08 ± 0.46, 6.04 ± 0.58, and 5.91 ± 0.32, respectively (numbers of replicated experiments, ). The obtained results confirmed that the ion-pair formation complexes are of high stability.

3.2. Validation of the Present Method

The proposed methods are validated according to ICH recommendations Q2(R1) [33]. The parameters that have been investigated are indicated below.

3.2.1. Linearity, Sensitivity, and Limits of Detection and Quantification

A linear relationship between the measured absorbance and the concentration range studied for each drug as shown in Figure 9 and the correlation coefficient (R) of at least 0.997 were achieved. The limit of detection (LOD) and quantification (LOQ) of the method are determined by and , respectively, where SD is the standard deviation of blank absorbance values and b is the slope of the calibration curve equation.

The LOD and LOQ values, slope, and intercept of linear graphs for all the drugs and analytical parameters are indicated in Table 2. The molar absorptivities and Sandell’s sensitivity of each methods were calculated and these values showed that the molar absorptivity of ion-pair complexes was in the order CFX-BTB > LFX-BTB > OFX-BTB.

ParametersProposed methods

Wavelengths λmax (nm)418415420
Stability (h)242424
Shaking time (min)222
Stoichiometric ratio1 : 11 : 11 : 1
Beer’s law range (µg/mL)1–350.5–250.5–25
Limit of detection, LOD (µg/mL)0.1050.1010.084
Limit of quantitation, LOQ (µg/mL)0.3150.3030.252
Molar absorptivity (L/ × 1042.07 × 1042.09 × 104
Sandell’s sensitivity (µg/cm2)0.0680.0480.046

Regression equation (Y = bx + a), where Y is the absorbance, a is the intercept, b is the slope, and x is the concentration in μg/mL
Slope (b)0.0400.0570.061
Intercept (a)0.01650.0720.089
Correlation coefficient (R)0.9980.9970.998

3.2.2. Accuracy and Precision

The accuracy and precision of the methods were determined by preparing solutions of three different concentrations of drug and analyzing them in six replicates. The precision of the proposed methods was evaluated as percentage relative standard deviation (RSD%) and accuracy as percentage relative error (RE%). The percentage relative error was calculated using the following equation:

The accuracy and precision were summarized in Table 3. The low values of the RSD and RE confirm the high precision and the good accuracy of the present method.

MethodAdditive concentration (μg/mL)Found concentration (μg/mL)Recovery (%)RSD (%)RE (%)




3.2.3. Robustness and Ruggedness

For the evaluation of the method robustness, some parameters were interchanged: pH, dye concentration, wavelength range, and shaking time. The capacity remains unaffected by small deliberate variations. Method ruggedness was expressed as RSD% of the same procedure applied by two analysts and using different instruments on different days. The results showed no statistical differences between different analysts and instruments, suggesting that the developed methods were robust and rugged (Table 4).

MethodDifferent instrumentsDifferent analysts

Ofloxacin-BTB pure ofloxacin (10 µg·mL−1) Mekopharm (200 mg ofloxacin per tablet)

Levofloxacin-BTB pure levofloxacin (10 µg·mL−1) Stada (500 mg levofloxacin per tablet)

Ciprofloxacin-BTB pure ciprofloxacin (10 µg·mL−1) Hasancip (500 mg ciprofloxacin per tablet)9.850.181.8310.120.252.47

3.2.4. Selectivity and Effect of Interferences

The effect of commonly utilized excipients in drug formulation was studied. The investigated FQs were studied with various excipients such as magnesium stearate, glucose, lactose, starch, and sodium chloride which were prepared in the proportion corresponding to their amounts in the real drugs with a final dosage of 10 µg/mL FQ. The effect of excipients on the determination of FQs was evaluated by recovery when determining FQs analyzed with the proposed method in the presence of excipient (Table 5).

Recovery (%) ± SD
ExcipientsAmount of excipient added (μg/mL)OfloxacinLevofloxacinCiprofloxacin

Magnesium stearate500102.04 ± 0.12101.23 ± 0.08998.53 ± 0.91
Glucose250100.17 ± 0.1699.04 ± 0.1499.08 ± 0.062
Lactose50099.92 ± 0.21100.20 ± 0.1299.73 ± 0.21
Starch200100.96 ± 0.2498.89 ± 0.13101.31 ± 0.17
Sodium chloride500100.13 ± 0.24100.15 ± 0.1199.75 ± 0.16

The results in Table 5 show that the recoveries are in the range of 98.53–102.04, demonstrating that there is no interference of excipients when FQs in drugs are quantified by extractive spectrophotometric using ion-pair formation with BTB. In other words, the present method has a high selectivity for determining FQs in its dosage forms.

3.3. Comparison with Other Spectrophotometric Methods

The proposed method compares with other reported methods. It has been observed that the extractive spectrophotometric method with BTB in the present study is of high sensitivity than other ones (Table 6). It also does not need heating, the product is stable for a longer time, and the interferences are minimum.

DrugReagentλmax (nm)Range of determination (μg/mL)Molar absorptivity (L/mol⋅cm)RemarksReference

CiprofloxacinCo (II) tetrathiocyanate62320–2408.38 × 102Less sensitive[34]
Supracene violet 35752.5–308.62 × 103Less sensitive[35]
Eosin Y5472–83.56 × 104Less stable colour[36]
Merbromin5452–151.23 × 104Addition of CNto inhibit Hg+2 ions
Ce(IV)- MBTH63010–50Involves shaking time[17]
Tris(o-phenanthroline) iron(II)5100.04–7.23.4 × 104Involves shaking time and heating[18]
Tris (bipyridyl) iron(II)5220.05–92.95 × 104Involves shaking time and heating
CL52016–96Involves shaking time and heating[16]
TCNE3350.25–15Involves shaking time and heating
Sudan II5500.8–7.15.3 × 104Narrow linear range[8]
Congo red5170.5–6.02.83 × 104
Gentian violet5850.5–102.21 × 104
Brilliant blue G6100.5–6.02.86 × 104Narrow linear range and required pH adjustment[37]
Bromocresol green4121–202.28 × 104Required pH adjustment[14]
BTB4200.5–252.09 × 104Highly sensitive with wide linear dynamic ranges, no heating, and no pH adjustmentThis study

LevofloxacinChloranilic acid52115–2501.2 × 103Less sensitive[14]
Bromocresol green4111–202.16 × 104Required pH adjustment
Eosin Y5472–84.83 × 104Less stable colour[36]
Merbromin5452–151.58 × 104Addition of CNto inhibit Hg+2 ions
Cobalt (II) tetrathiocyanate62320–240Less sensitive[34]
Bromophenol blue4241.85–31.51.98 × 104Required pH adjustment[19]
Bromocresol green4281.85–251.82 × 104
BTB4150.5–252.07 × 104Highly sensitive with wide linear dynamic ranges, no heating, and no pH-adjustmentThis study

OfloxacinSupracene violet 35752.5–251.09 × 104Less sensitive[35]
Tropaeolin 0004852.5–308.23 × 102Less sensitive
Sudan II5600.8–8.42.97 × 104Narrow linear range[8]
Congo red5300.5–5.53.29 × 104
Gentian violet5750.8–112.51 × 104
Bromocresol purple4001.0–16.02. 4 × 104Required pH adjustment[38]
Bromocresol green4101.0–16.01.96 × 104Required pH adjustment
Bromophenol blue4105–251.03 × 104Required close pH control and involved extraction steps[20]
Bromothymol blue4152–152.01 × 104
Bromocresol purple4102–201.64 × 104
Bromothymol blue4151–351.44 × 104Highly sensitive with wide linear dynamic ranges, no heating, and no pH-adjustmentThis study

3.4. Analysis of Pharmaceutical Formulations

The proposed method was applied successfully for the determination of studied drugs in the pharmaceutical formulations (tablets and infusion) and the results are presented in Table 7. Six replicated determinations were measured. Table 7 shows that satisfactory recovery data were obtained and the recovery efficiency varies from 97.41% to 101.20%, indicating high accuracy of the present method in determining real pharmaceutical samples.

Pharmaceutical preparationHasancip tabletKacipro tabletShandong infusionHebei infusionLevofloxacin StadaLevofloxacin DHGOfloxacin mekopharm

Labeled amount (mg/form)500/tablet500/tablet200/100 mL200/100 mL500/tablet500/tablet200/tablet
Recovery (%) ± SD98.89 ± 0.23101.20 ± 0.2097.41 ± 0.4297.69 ± 0.3699.53 ± 0.17101.01 ± 0.3599.58 ± 0.46

3.5. Comparison with HPLC-MS Method

In order to validate the experimental data in determining some real drug samples, HPLC-MS was used with the conditions described on Section 2.6 according to the previously published paper [13]. The comparison between the results determined by the present method with HPLC-MS method was indicated in Table 8.

SampleAmount (mg/tablet)Difference (%)
Proposed methodHPLC -MS

Ciprofloxacin-Hasancip table494.45 ± 11.63446.93 ± 15.8410.63
Ofloxacin mekopharm199.16 ± 0.85202.00 ± 2.72−1.41
Levofloxacin DHG505.05 ± 17.33480.55 ± 54.165.10
Levofloxacin Stada497.65 ± 9.24486.04 ± 9.242.39

Table 8 shows a good agreement between the proposed method and HPLC-MS where the relative differences of two methods were less than 11%. Furthermore, the standard deviation of the proposed method is almost lower than that of HPLC-MS. Our results indicate that the extractive spectrophotometric determination of FQs using BTB dye in chloroform is a very good method to quantify the FQ in pharmaceutical formulations.

4. Conclusions

We have reported a new method when using BTB as an anionic dyes for the extractive spectrophotometric determination of ciprofloxacin (CFX), levofloxacin (LFX), and ofloxacin (OFX) in different pharmaceutical drugs (tablets and infusions). The methods have the advantages of simplicity without heating, pH-adjustment, and high sensitivity. The limit of detection (LOD) values are 0.084 µg/mL for CFX, 0.101 µg/mL for LFX, and 0.105 µg/mL for OFX. No interference from common excipients was confirmed. The stoichiometry complexes of FQs and BTB determined by Job’s method of continuous variation were found to be 1 : 1. The developed and validated methods are indicated as the acceptable precision and accuracy, and recovery of the drugs and suitable for routine analysis of drugs in pharmaceutical formulations. The results of some real samples by the present method that were compared with HPLC-MS method with the relative differences are less than 11%, indicating that the present method is good for determination of FQs in pharmaceutical formulations.

Data Availability

The data used to support the findings of this study are available from the corresponding author upon request.

Conflicts of Interest

The authors declare that they have no conflicts of interest.


This work was supported financially by the project of Le Quy Don Technical University, under 11/HLKT/2017 project. The authors would like to thank the National Institute for Food Control (Vietnam) for providing HPLC-MS system to validate the present method.


  1. V. Kapetanovic, L. Milovanovic, and M. Erceg, “Spectrophotometric and polarographic investigation of the Ofloxacin-Cu(II) complexes,” Talanta, vol. 43, no. 12, pp. 2123–2130, 1996. View at: Publisher Site | Google Scholar
  2. Y. Khaliq and G. G. Zhanel, “Fluoroquinolone-associated tendinopathy: a critical review of the literature,” Clinical Infectious Diseases, vol. 36, no. 11, pp. 1404–1410, 2003. View at: Publisher Site | Google Scholar
  3. G. G. Zhanel, K. Ennis, L. Vercaigne et al., “A critical review of the fluoroquinolones,” Drugs, vol. 62, no. 1, pp. 13–59, 2002. View at: Publisher Site | Google Scholar
  4. Y. Ni, Y. Wang, and S. Kokot, “Simultaneous determination of three fluoroquinolones by linear sweep stripping voltammetry with the aid of chemometrics,” Talanta, vol. 69, no. 1, pp. 216–225, 2006. View at: Publisher Site | Google Scholar
  5. H. Ma, X. Zheng, and Z. Zhang, “Flow-injection electrogenerated chemiluminescence determination of fluoroquinolones based on its sensitizing effect,” Luminescence, vol. 20, no. 4-5, pp. 303–306, 2005. View at: Publisher Site | Google Scholar
  6. S. T. Ulu, “Spectrofluorimetric determination of fluoroquinolones in pharmaceutical preparations,” Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy, vol. 72, no. 1, pp. 138–143, 2009. View at: Publisher Site | Google Scholar
  7. L. M. Du, A. P. Lin, and Y. Q. Yang, “Spectrofluorimetric determination of certain fluoroquinolone through charge transfer complex formation,” Analytical Letters, vol. 37, no. 10, pp. 2175–2188, 2004. View at: Publisher Site | Google Scholar
  8. A. S. Amin, M. E. Moustafa, and R. M. S. El‐Dosoky, “Spectrophotometric determination of some fluoroquinolone derivatives in dosage forms and biological fluids using ion‐pair complex formation,” Analytical Letters, vol. 41, no. 5, pp. 837–852, 2008. View at: Publisher Site | Google Scholar
  9. A. M. A.-E. El-Didamony and O. Mona, “Kinetic spectrophotometric method for the determination of some fourth generation fluoroquinolones in bulk and in pharmaceutical formulations,” Journal of Saudi Chemical Society, vol. 21, pp. S58–S66, 2017. View at: Publisher Site | Google Scholar
  10. M. I. R. M. Santoro, N. M. Kassab, A. K. Singh, and E. R. M. Kedor-Hackmam, “Quantitative determination of gatifloxacin, levofloxacin, lomefloxacin and pefloxacin fluoroquinolonic antibiotics in pharmaceutical preparations by high-performance liquid chromatography,” Journal of Pharmaceutical and Biomedical Analysis, vol. 40, no. 1, pp. 179–184, 2006. View at: Publisher Site | Google Scholar
  11. G. Carlucci, “Analysis of fluoroquinolones in biological fluids by high-performance liquid chromatography,” Journal of Chromatography A, vol. 812, no. 1-2, pp. 343–367, 1998. View at: Publisher Site | Google Scholar
  12. H. Ziarrusta, N. Val, H. Dominguez et al., “Determination of fluoroquinolones in fish tissues, biological fluids, and environmental waters by liquid chromatography tandem mass spectrometry,” Analytical and Bioanalytical Chemistry, vol. 409, no. 27, pp. 6359–6370, 2017. View at: Publisher Site | Google Scholar
  13. L. Johnston, L. Mackay, and M. Croft, “Determination of quinolones and fluoroquinolones in fish tissue and seafood by high-performance liquid chromatography with electrospray ionisation tandem mass spectrometric detection,” Journal of Chromatography A, vol. 982, no. 1, pp. 97–109, 2002. View at: Publisher Site | Google Scholar
  14. A. M. El-Brashy, M. E.-S. Metwally, and F. A. El-Sepai, “Spectrophotometric Determination of Some Fluoroquinolone Antibacterials through Charge-transfer and Ion-pair Complexation Reactions,” Bulletin of the Korean Chemical Society, vol. 25, no. 3, pp. 365–372, 2004. View at: Publisher Site | Google Scholar
  15. L. M. Du, H. Y. Yao, and M. Fu, “Spectrofluorimetric study of the charge-transfer complexation of certain fluoroquinolones with 7,7,8,8-tetracyanoquinodimethane,” Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy, vol. 61, no. 1-2, pp. 281–286, 2005. View at: Publisher Site | Google Scholar
  16. S. Mostafa, M. El-Sadek, and E. A. Alla, “Spectrophotometric determination of ciprofloxacin, enrofloxacin and pefloxacin through charge transfer complex formation,” Journal of Pharmaceutical and Biomedical Analysis, vol. 27, no. 1-2, pp. 133–142, 2002. View at: Publisher Site | Google Scholar
  17. M. Rizk, F. B., F. Ibrahim, S. M. Ahmed, and N. M. El-Enany, “A simple kinetic spectrophotometric method for the determination of certain 4-quinolones in drug formulations,” Scientia Pharmaceutica, vol. 68, no. 2, pp. 173–188, 2000. View at: Google Scholar
  18. B. S. Nagaralli, J. Seetharamappa, and M. B. Melwanki, “Sensitive spectrophotometric methods for the determination of amoxycillin, ciprofloxacin and piroxicam in pure and pharmaceutical formulations,” Journal of Pharmaceutical and Biomedical Analysis, vol. 29, no. 5, pp. 859–864, 2002. View at: Publisher Site | Google Scholar
  19. S. Ashour and R. Al-Khalil, “Simple extractive colorimetric determination of levofloxacin by acid-dye complexation methods in pharmaceutical preparations,” Farmaco, vol. 60, no. 9, pp. 771–775, 2005. View at: Publisher Site | Google Scholar
  20. Y. M. Issa, F. M. Abdel-Gawad, M. A. Abou Table, and H. M. Hussein, “Spectrophotometric determination of ofloxacin and lomefloxacin hydrochloride with some sulphonphthalein dyes,” Analytical Letters, vol. 30, no. 11, pp. 2071–2084, 1997. View at: Publisher Site | Google Scholar
  21. H. A. Omara and A. S. Amin, “Extractive-spectrophotometric methods for determination of anti-Parkinsonian drug in pharmaceutical formulations and in biological samples using sulphonphthalein acid dyes,” Journal of Saudi Chemical Society, vol. 16, no. 1, pp. 75–81, 2012. View at: Publisher Site | Google Scholar
  22. A. A. Gouda, A. S. Amin, R. El-Sheikh, and A. G. Yousef, “Spectrophotometric determination of gemifloxacin mesylate, moxifloxacin hydrochloride, and enrofloxacin in pharmaceutical formulations using acid dyes,” Journal of Analytical Methods in Chemistry, vol. 2014, Article ID 286379, 16 pages, 2014. View at: Publisher Site | Google Scholar
  23. S. G. Nair, J. V. Shah, P. A. Shah, M. Sanyal, and P. S. Shrivastav, “Extractive spectrophotometric determination of five selected drugs by ion-pair complex formation with bromothymol blue in pure form and pharmaceutical preparations,” Cogent Chemistry, vol. 1, no. 1, Article ID 1075852, 2015. View at: Publisher Site | Google Scholar
  24. N. Rahman and S. N. Hejaz-Azmi, “Extractive spectrophotometric methods for determination of diltiazem HCl in pharmaceutical formulations using bromothymol blue, bromophenol blue and bromocresol green,” Journal of Pharmaceutical and Biomedical Analysis, vol. 24, no. 1, pp. 33–41, 2000. View at: Publisher Site | Google Scholar
  25. H. E. Abdellatef, “Extractive-spectrophotometric determination of disopyramide and irbesartan in their pharmaceutical formulation,” Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy, vol. 66, no. 4, pp. 1248–1254, 2007. View at: Publisher Site | Google Scholar
  26. N. Rahman, S. K. Manirul Haque, S. N. H. Azmi, and H. Rahman, “Optimized and validated spectrophotometric methods for the determination of amiodarone hydrochloride in commercial dosage forms using N-bromosuccinimide and bromothymol blue,” Journal of Saudi Chemical Society, vol. 21, no. 1, pp. 25–34, 2017. View at: Publisher Site | Google Scholar
  27. D. Taşkın, G. Erensoy, and S. Sungur, “Optimized and validated spectrophotometric determination of butamirate citrate in bulk and dosage forms using ion-pair formation with methyl orange and bromothymol blue,” Farmacia, vol. 65, pp. 761–765, 2017. View at: Google Scholar
  28. P. Govardhan Reddy, V. Kiran Kumar, V. Appala Raju, J. Raghu Ram, and N. Appala Rraju, “Novel spectrophotometric method development for the estimation of boceprevir in bulk and in pharmaceutical formulations,” Research Journal of Pharmacy and Technology, vol. 10, p. 4313, 2017. View at: Publisher Site | Google Scholar
  29. A. Sakur and S. Affas, “Direct spectrophotometric determination of sildenafil citrate in pharmaceutical preparations via complex formation with two sulphonphthalein acid dyes,” Research Journal of Pharmacy and Technology, vol. 10, p. 1191, 2017. View at: Publisher Site | Google Scholar
  30. K. N. Prashanth, K. Basavaiah, and K. B. Vinay, “Sensitive and selective spectrophotometric assay of rizatriptan benzoate in pharmaceuticals using three sulphonphthalein dyes,” Arabian Journal of Chemistry, vol. 9, pp. S971–S980, 2016. View at: Publisher Site | Google Scholar
  31. T. D. Nguyen, L. Bau, L. Q. Thao, and N. Dang Dat, “Extractive spectrophotometric methods for determination of ciprofloxacin in pharmaceutical formulations using sulfonephthalein acid dyes,” Vietnam journal of chemistry, vol. 55, no. 6, pp. 767–774, 2017. View at: Publisher Site | Google Scholar
  32. H. T. S. Britton, Hydrogen Ions, Chapman & Hall, 4th edition, 1952.
  33. I. T. Q. (R1), Validation of Analytical Procedures: Text and Methodology, ICH Secretariat, Geneva, Switzerland, 2010, (CPMP/ICH/281/95).
  34. A. M. El-Brashy, M. E.-S. Metwally, and F. A. El-Sepai, “Spectrophotometric determination of some fluoroquinolone antibacterials by ion-pair complex formation with cobalt (II) tetrathiocyanate,” Journal of the Chinese Chemical Society, vol. 52, no. 1, pp. 77–84, 2005. View at: Publisher Site | Google Scholar
  35. C. S. P. Sastry, K. R. Rao, and D. S. Prasad, “Extractive spectrophotometric determination of some fluoroquinolone derivatives in pure and dosage forms,” Talanta, vol. 42, no. 3, pp. 311–316, 1995. View at: Publisher Site | Google Scholar
  36. A. M. El-Brashy, M. El-Sayed Metwally, and F. A. El-Sepai, “Spectrophotometric determination of some fluoroquinolone antibacterials by binary complex formation with xanthene dyes,” Farmaco, vol. 59, no. 10, pp. 809–817, 2004. View at: Publisher Site | Google Scholar
  37. B. G. Gowda and J. Seetharamappa, “Extractive spectrophotometric determination of fluoroquinolones and antiallergic drugs in pure and pharmaceutical formulations,” Analytical Sciences, vol. 19, no. 3, pp. 461–464, 2003. View at: Publisher Site | Google Scholar
  38. K. N. Prashanth, K. Basavaiah, and M. S. Raghu, “Simple and selective spectrophotometric determination of ofloxacin in pharmaceutical formulations using two sulphonphthalein acid dyes,” ISRN Spectroscopy, vol. 2013, Article ID 357598, p. 9, 2013. View at: Publisher Site | Google Scholar

Copyright © 2018 Trung Dung Nguyen et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

More related articles

1205 Views | 404 Downloads | 1 Citation
 PDF  Download Citation  Citation
 Download other formatsMore
 Order printed copiesOrder

Related articles

We are committed to sharing findings related to COVID-19 as quickly and safely as possible. Any author submitting a COVID-19 paper should notify us at to ensure their research is fast-tracked and made available on a preprint server as soon as possible. We will be providing unlimited waivers of publication charges for accepted articles related to COVID-19. Sign up here as a reviewer to help fast-track new submissions.