New Spectrophotometric Methods for the Estimation of Cefditoren Pivoxil

S Appala Raju*, Arvind B Karadi and Shobha Manjunath

HKE’s College of Pharmacy, Gulbarga-585 105 (KS) India

*Corresponding Author E-mail: arvindabk@rediffmail.com

ABSTRACT

Two simple and sensitive spectrophotometric methods (A and B) for the quantitative estimation of cefditoren pivoxil in bulk drug and pharmaceutical preparations. These methods are based on diazotization of cefditoren with nitrous acid followed by coupling in situ with phloroglucinol (method-A), Resorcinol (method-B) to yield orange yellow colored chromogen and exhibits absorption maximum at 462 and 455 nm respectively. Colored chromogens are stable for 4-6 hrs. and obeyed Beer’s law in the concentration range of 20-80 mg/ml. and 10-50 mg/ml. for (method-A and B) respectively. The results of analysis for the two methods have been validated statistically and by recovery studies. The results are comparing with those obtained using UV spectrophotometric method in 0.1 N HCl at 233 nm.

KEYWORDS: Cefditoren, resocinol, phloroglucinol, spectrophotometry

INTRODUCTION:

Cefditoren pivoxil is a third Generation cephalosporin antibiotic for oral use, indicated for the treatment of mild and moderate infections in adults and adolacents which are caused by susceptible strains of the designated microorganisms used to treat community acquired pneumonia, transilities etc. Cefditoren pivoxil is chemically (-)-(6R,7R)-2,2-dimethylpropionyloxymethyl 7-[(Z)-2-(2-aminothiazol-4-yl)-2 methoxy iminoacetamido]-3-[(Z)-2-(4-methylthiazol-5-yl)ethenyl]-8-oxo-5-thia-1,azabicyclo[4.2.0] oct-2-ene-2-carboxylate. It is not official in any pharmacopiea. Spectrophotometric analytical reports are not found in literature for its quantitative estimation in Bulk drug and pharmaceutical dosage forms. Hence it was thought worthwhile to develop Spectrophotometric method for the same. This paper describes two simple, sensitive and economical visible spectrophotometric methods (A and B) for the quantitative estimation of cefditoren pivoxil.

MATERIAL AND METHODS:

Instrumentation:

All the spectral measurements were made on systronics UV visible spectrophotometer model 119 with 1cm matched quartz cells was used.

Chemical and reagents:

All chemicals used were of analytical grade reagents.

Pholoroglucinol : 1% w/v in double distilled alcohol

Sodium Nitrite : 0.1%, 0.5% w/v in deionised water.

Resocinol : 0.5% w/v in deionised water

Sodium Hydroxide: 2% w/v in deionised water

Hydrochloric acid : 0.1 N in deionised water and Conc. Hydrochloric acid

STANDARD AND SAMPLE SOLUTIONS:

Cefditoren (pure or formulation)-100 mg was accurately weighed and dissolved in 0.1 N HCl (20ml) and transferred to standard 100ml volumetric flask. The volume was made upto the mark with 0.1 N HCL (1mg/ml). Final concentration was brought upto 100 mg/ml with 0.1N HCL, Incase of formulation 20 tablets of cefditoren pivoxil each containing 200mg were accurately weighed and powedered, 100mg of powdered drug equivalent were taken for the study.

ASSAY:

Method-A:

Aliquots of drug ranging from 0.2 to 0.8 ml (1ml=100mg/ml) were transferred in to a series of 10ml volumetric flasks. To each flasks 0.5ml of Conc. HCl, 1ml of sodium nitrite (1% w/v) were added at room temperature thoroughly shaken, after 10 minutes, 1ml of phloroglucinol (1% w/v) was added.

Table-1.Optical Characteristics, precision ad accuracy of the proposed methods for cefditoren pivoxil

	Method-A	Method-B
lmax (nm)	462	455
Beer’s Law (mg/ml)	20-80	10-50
Molar absorptivity (L/mol‑1cm-1)	5.403x103	1.1503x104
Sandell’s sensitivity (mg/ml/cm² 0.001 absorbance unit)	0.059	0.095
% RSD	2.371x104	2.557x103
Regression equation (*)
Slope (b)	0.01015742	0.01138
Intercept (a)	0.063714	0.0638
Correlation coefficient (r)	0.9999	0.999
% RSD	2.371x104	2.55x103
Range of error**
Confidence limits with 0.01 level.	1.30398	1.30298
Confidence limits with 0.05 level.	0.8806	0.8808

*y = bc + a, y is the absorbance unit and c is the concentration in mg/ml, **eight measurements

The volume was made up to the mark with 0.1 N HCL. The absorbance of the orange yellow coloured coromogen was measured at 462 nm against reagent blank. The colour was stable for 4-6 hrs. The amount of cefditoren pivoxil sample present was computed from calibration curve.

Method-B:

Aliquots of drug raging from 0.1 to 0.5 ml (1ml = 100 mg/ml) were transferred into a series of 10 ml volumetric flasks. To each flasks 0.5 ml of Conc. HCl, 1 ml of solution of sodium nitrite (0.5 % w/v) were added, shaken gently for 10 min. at room temperature 1ml of 2% NaOH and 0.1 ml of resocinol (0.5% w/v) and were added and the volume was made upto mark with 0.1N HCl. The absorbance of the coloured (orange) chromogen was measured at 455 nm against reagent blank. The colour was stable for 4-5 hr. The amount of drug present in the sample was computed from calibration curve.

The results of the above method were compared with the results obtained with UV method. In UV method the drug solution of cefditoren pivoxil in 0.1 N HCl either in pure or formulation 100 mg/ml was prepared. Aliquots ranging from 0.01 to 0.05 ml (1ml=100 mg/ml) were transferred in to a series of 10 ml volumetric flasks the volume was made upto mark with 0.1 N HCl, absorbance was measured at 233 nm.

RESULTS AND DISCUSSION:

The presence of amine group in cefditoren pivoxil enabled the use of diazotization of the drug with nitrous acid and coupling the resulting diazomium salt with phloroglucinol and resorcinol. So to form orange yellow and orange chromogen respectively exhibiting lmax 462 and 455 nm. The Beer’s law obeyed by these methods in the concentration range 20-80 and 10-50 mg/ml respectively.

The vary fact that neither the drug nor the reagents used displayed any peaks at 462 and 455 nm respectively proves beyond doubt that the drug has undergone reactions quantitatively with the above reagents.

Optical characteristics such as Beer’s Law limits, absorption maxima, molar absorptivity, sandell’s sensitivity, percent relative standard deviation (%RSD) and percent range of error (0.01 and 0.05 level) were calculated for the above methods and summarized in Table-1, optimum conditions for colour development in each method were established by varying the parameters one at a time and keeping the other parameter fixed, while observing effects on the absorbance of the coloured species.

Figure-1: Absorption maxima of cefditoren pivoxil with pholoroglucinol

The optimum Concentration for the estimation of drug was established by varying the drug concentration, keeping reagent concentration fixed. After establishing the optimum concentration for drug, the reagent concentration was chosen for he studies. The colored species formed gave better absorbance and obeyed Beer’s Law statically. The values obtained for the determination of cefditoren pivoxil in tablet sample by the proposed and UV method are compared in Table-2.To evaluate the validity and reproducibility of the method, known amount of the pure drug were added to the previously analysed pharmaceutical preparation. The % recovery is shown in Table-2.

Table-2 Estimation of cefditoren pivoxil in pharmaceutical preparations

Sample tablets	Labeled amount (mg)	Amount obtained (mg)			% Recovery*
		Proposed method			Proposed method
		A	B	UV Method**	A	B	UV method
T1	200 mg	199.58	199.80	199.60	99.91	99.85	99.60

** UV method developed in our laboratory, * Recovery amount was the average of five determinations

Figure-2: Calibration curve of cefditoren pivoxil with phloroglucinol

Figure-3: Absorption maxima of cefditoren pivoxil with resocinol

The methods reported here found to be simple, sensitive, accurate, and precise. The reaction occurs at room temperature. These methods involves simple instrument which is cost effective compared with other instrumental techniques. The present work involved the formation of highly stable color species (4-6 hrs) which make it easier for the determination of cefditoren pivoxil from pharmaceutical formulation in a routine manner. These methods reveals that, the common Excipients usually present in the tablet dosage from did not interfere at their regularly added levels.

Figure-4: Calibration curve of cefditoren pivoxil with resorcinol

ACKNOWLEDGEMENTS:

The authors are thankful to Ranbaxy Laboratories Solan for providing gift sample of drug for research and management, The principal HKES College of Pharmacy Gulbarga for providing necessary laboratory facilities.

REFERENCES:

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Received on 29.04.2009 Modified on 18.06.2009

Asian J. Research Chem. 2(3): July-Sept. 2009 page 270-272