Application of Oxidants to the Spectrophotome

tric Determination of Cephalosporins (Cefditoren Pivoxil and Cefdinir) In Formulations

 

Srinivasa Rao Narala¹* and K. Saraswathi²

¹Department of Chemistry, R.V.R. and J.C. College of Engineering, Guntur, A.P., India

²Department of Chemistry, S.V. University, Tirupathi, A.P., India

*Corresponding Author E-mail: srinunarala@gmail.com

ABSTRACT:

Three new spectrophotometric methods (A, B and C) for the determination of Cephalosporins (Cefditoren Pivoxil and Cefdinir) have been proposed. These methods are based on the oxidation of the drug with Fe (III) and the estimation of Fe (II) produced after chelation with either 1,10- Phenanthroline or 2,2’-Bipyridyl or Potassium Ferricyanide at 510, 525, 730 nm (for Cefditoren Pivoxil) and at 512, 510, 700 nm (for Cefdinir). The Beer’s law was obeyed in the concentration range of 4-20, 4-20, 2-10 µg/ml (for Cefditoren Pivoxil) and 2-8, 8-24, 4-12µg/ml (for Cefdinir) for methods A, B and C respectively. Thus results of the proposed methods were validated statistically and applied successfully to the determination of Cefditoren Pivoxil and Cefdinir in bulk and its pharmaceutical formulations without any interference from excipients.

 

 

 

INTRODUCTION:

Cefditoren Pivoxil is chemically (6R)-7-[[(2Z)-2-(2-amino -1,3-thiazool-4-yl)-2-methoxyiminoacetyl]amino]-3-[(Z)-2-(4-methyl-1,3-thiazol-5-yl)ethenyl]-8-oxo-5-thia-1- aza bicyclo [4.2.0] oct-2-ene-2-carboxylic acid. It is a third generation cephalosporin with antibacterial activity against gram-positive and gram-negative pathogens.

 

Cefdinir is chemically (6R,7R)-7-[[(2Z)-2-(2-amino-1,3-thiazol-4-yl)-2-hydroxyiminoacetyl]amino]-3-ethenyl-8-oxo-5 - thia-1-azabicyclo [4.2.0] oct-2-ene-2-carboxylic acid. It is a semi-synthetic, broad-spectrum antibiotic in the third generation of the cephalosporin class, proven effective for common bacterial infections of the ear, sinus, throat and skin. Few analytical methods^1-9 have been reported for the estimation of Cefditoren Pivoxil and Cefdinir. The proposed methods are simple, sensitive and accurate for the determination of Cefditoren Pivoxil and Cefdinir in bulk and pharmaceutical dosage forms.

 

EXPERIMENTAL:

Apparatus:

All spectral and absorbance measurements were made on a Techcomp UV – 2301 UV-Visible spectrophotometer with 1 cm matched quartz cells.

 

Materials and reagents:

All chemicals used were of analytical grade. Cephalosporins (pharmaceutical grade) were obtained from local pharmaceutical laboratories, Hyderabad and commercial formulations were procured from the market. Aqueous solutions of 1, 10- Phenanthroline or 2,2’-bipyridyl (0.01 M), Ferric chloride( 0.003 M) and Ortho phosphoric acid (0.2 M) were prepared for methods A and B. Aqueous solutions of Ferric chloride (0.5% w/v), Potassium ferricyanide (0.2% w/v) and 1N HCl were prepared for method C.

 

Stock solutions (1 mg/ml) of Cefditoren pivoxil and Cefdinir were freshly prepared with pure samples by dissolving 100 mg in 100 ml of solvent (methanol for Cefditoren pivoxil and dimethyl sulfoxide for Cefdinir). From this suitable dilutions were made to obtain working standard concentrations i.e 100 µg/ml, 200 µg/ml, 100 µg/ml (for Cefditoren Pivoxil and Cefdinir) for methods A, B and C, respectively.

 

Procedure for Calibration Curve:

In method A and B different aliquots of working standard solution of Cephalosporins (100 µg/ml and 200 µg/ml) ranging from 0.5 – 5 ml were added to a series of heating tubes. To each tube 1 ml of ferric chloride and 1 ml of 1,10-Phenanthroline or 2,2’ bipyridyl were added and heated for 15 min. at 100°C on a water bath and then cooled to room temperature and 2 ml of ortho phosphoric acid was added. The contents of the tubes were transferred to a series of 25 ml standard flasks, then diluted to the mark with distilled water.  

Table-1. Optical characteristics of the proposed methods for Cefditoren Pivoxil and  Cefdinir

Parameter	Cefditoren Pivoxil			Cefdinir
	Method A	Method B	Method C	Method A	Method B	Method C
λ max	510	525	730	512	510	700
Beer’law limits(µg/ml)	4-20	4-20	2-10	2-8	8-24	4-12
Molar absorptivity ( l mol-1 cm-1)	0.3333X104	1.9459X103	5.3009X103	0.2991X104	0.7176X103	1.423X103
Sandell’sensitivity ( µg cm-2)	0.1862	0.3189	0.1171	0.1322	0.5509	0.2777
Regression equation ( Y= mX+b )
Slope ( m )	0.0739	0.0465	0.0983	0.1496	0.0316	0.0322
Intercept ( b )	0.109	0.0715	0.1224	0.3185	0.1108	- 0.0048
Correlation coefficient	0.9997	0.9999	0.9983	0.9989	0.9999	0.9998
R.S.D.(%)*	0.6082	0.7813	0.7844	1.1291	0.4436	0.4701
% Range of error (confidence limits)
0.05 level	± 0.7551	± 0.9699	± 0.9746	± 1.4046	± 0.5507	± 0.5848
0.01 level	± 1.2523	± 1.6087	± 1.6164	± 2.3295	± 0.9134	± 0.9699

* Mean of five determinations

 

Table-2.   Mean ± S.D amount of Cefditoren Pivoxil and Cefdinir found in formulations by proposed methods

Drug	Fomulation type	Labeled amount mg/tablet or capsule	Amount found by proposed methods*
			Method A	Method B	Method C
Cefditoren   Pivoxil	Tablet-1	200	199.87±0.063	199.90±0.089	199.95±0.083
	Tablet-2	200	199.92±0.072	199.95±0.084	199.94±0.082
Cefdinir	Capsule-1	300	299.85±0.070	299.88±0.056	299.96±0.082
	Capsule-2	300	299.94±0.095	299.91±0.086	299.90±0.121

* Mean of five determinations

 

The absorbance of each solution was measured at 510 nm (for method A) or 525 nm (for method B) in case of Cefditoren Pivoxil and at 512 nm (for method A) or 510 nm (for method B) in case of Cefdinir against the reagent blank. The calibration graph was constructed by plotting the absorbance versus concentration of the drug. The concentration of unknown was read from the calibration graph.

 

In method C different aliquots of working standard solution of Cephalosporins (100 µg/ml) ranging from 0.5 – 5 ml were transferred to a series of 25 ml standard flasks. To each flask 1 ml of ferric chloride and 2 ml of Potassium ferri cyanide were added and kept for 10 min. To this 1 ml of 1 N HCl is added and the volume is made up to the mark with distilled water. The absorbance of each solution was measured at 730 nm (for Cefditoren Pivoxil) or at 700 nm (for Cefdinir) against the reagent blank and the calibration graph was constructed. The concentration of unknown was read from the calibration graph.

 

Procedure for analysis of formulations:

Twenty tablets or capsules were weighed accurately and ground into a fine powder. An amount of powder equivalent to 100 mg of Cefditoren Pivoxil or Cefdinir was transferred in to a 100 ml volumetric flask, 50 ml of the solvent was added and sonicated for 10 min. then the volume was made up to the mark with the solvent, mixed well and filtered using a Whatmann filter paper. The assay of the tablets or capsules was carried out according to the general procedure by referring to calibration plots constructed above.

 

RESULTS AND DISCUSSION :

The proposed methods are based on the oxidation of Cefditoren Pivoxil or Cefdinir by ferric salt and the reduced state of iron was utilized for the formation of colored complex on treatment with 1,10 -Phenanthroline or 2,2’– bipyridyl or Potassium ferri cyanide. Optical characteristics such as molar absorptivity, sandell’s sensitivity, precision and accuracy are summarized in Table-1. The measured relative standard deviation and confidence limits were considered satisfactorily for all these methods. The average drug content found by proposed methods is given in Table- 2.

 

CONCLUSION :

The proposed methods are simple, accurate, sensitive and are suitable for the determination of Cefditoren Pivoxil and Cefdinir in pharmaceutical formulations without interference from the excipients and also for quality control in the pharmaceutical laboratories.

 

ACKNOWLEDGEMENTS:

The authors are thankful to the management R.V.R. and J.C. College of engineering, Guntur for supporting to carrying out these investigations.

 

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Received on 07.10.2010        Modified on 27.10.2010

Accepted on 04.11.2010        © AJRC All right reserved