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Development of Spectrophotometric Methods for the Determination of Cefixime in Capsule and Suspension by Making Complex with Cobalt Chloride and Cobalt Nitrate.

Byline: SYED SAEED-UL-HASSAN, MUHAMMAD TAYYAB ANSARI, SHUMILA SADAF, IMRAN TARIQ AND ZAHID MAHMOOD

Summary: The purpose of the study was to develop a new spectrophotometric method for the determination of cefixime trihydrate using cobalt salts i.e. cobalt chloride and cobalt nitrate. Cefixime exhibited lmax at 256nm in cobalt chloride while cobalt nitrate complexes showed lmax at 211nm, Cefixime obeyed bear's law after complexation with these salts for concentration ranges at 0.1-0.6ug/ml and 0.1-1.5ug/ml respectively. The proposed method was validated using international council of harmonization (ICH) guidelines. Limits of detection (LOD) as well as limit of quantitation (LOQ) for cobalt chloride were 0.03ug/ml and 0.01ug/ml while these values were 0.09ug/ml and 0.05ug/ml for cobalt nitrate respectively. Statistical approaches showed that result of proposed methods are not only significant but also reproducible and more reliable than currently reported methods.

Percentage relative standard deviation (%RSD) values were less than 2% for proposed methods which illustrate the good precision. In addition these methods do not need any prior extraction to estimate drug in raw material, capsule and suspension compared to other reported methods. It was concluded that proposed methods are versatile, cheaper, less time consuming, selective and rapid for the determination of cefixime in these formulations.

Key Words: Cefixime, Spectrophotometry, Cobalt nitrate, Validation.

Introduction

Cefixime is a third-generation b-lactam antibiotic used in treatment of various infections caused by gram negative bacteria and anaerobic bacteria [1]. Cefixime trihydrate has many chemical names i.e. 5-Thia-1-azabicyclo[4.2.0]oct-2-ene-2- carboxylicacid, 7-[[(2-amino-4-thiazolyl) [(carboxymethoxy) imino] acetyl]amino]-3-ethenyl- 8-oxo-trihydrate, [6R-[6a,7b(Z)]]-.(6R,7R)-7-[2-(2- Amino-4-thiazolyl)glyoxylamido]-8-oxo-3-vinyl-5- thia-1 azabicyclo[4.2.0]oct-2-ene-2-carboxylicacid, 72-(Z)-[O (carboxymethyl) oxime] trihydrate [2-4]. (Fig. 1)

Cefixime trihydrate is available in various dosage forms such as capsule, suspension and tablet. Different analytical methods have been reported for the determination of cefixime which include High performance liquid chromatography [5, 6] , conventional spectrophotometric method and High pressure thin layer chromatography [7], rapid and sensitive RP- HPLC method [8] and voltametric determination [9]. Luminol-Cu2+ reaction with cefixime made possible estimation with spectrophotometric method at the level of 0.8ug/ml [10] and fluorimetric determination of cefixime in raw material and dosage forms [11]. Different hydrotropic agents have also been employed for the spectrophotometric determination of cefixime due to its water insolubility [12]. As the complex formation of drug always showed a better biological activity as compared to the drug alone. Literature survey revealed that there is no new spectrophotometric methods of cefixime with it complex with cobalt were available.

S the aim of the present study was to develop new improved spectrophotometric method using salts of cobalt (cobalt chloride and cobalt nitrate) for cefixime raw material as well as in capsules and suspension that contain cefixime trihydrate as an active ingredient. The proposed method was also validated for various parameters i.e. linearity, precision, accuracy, limit of quantitation and limit of detection in raw material, suspension as well as in capsule as per international council harmonization (ICH) guidelines and others [13-16].

Results and Discussion

Linearity

Six concentrations of cefixime trihydrate equivalent to 0.1-0.6 ug/ml were prepared and checked for their absorbance (Table-1). The linearity of detector response was established by plotting a

The proposed method was superior to the previously reported UV-based spectrophotometric methods for the analysis of cefixime with cobalt chloride and cobalt nitrate. So the obtained complexes can be utilized in the development of simple, rapid and accurate spectrophotometric methods for the analysis of cefixime in different pharmaceutical dosage forms. In addition, the proposed methods were applied using a simple spectrophotometer, which is available in all quality control laboratories.

Experimental

Chemicals

Standard and raw cefixime (Intas pharmaceuticals Ltd. India), Methanol (Merck Ltd., Germany), Cobalt chloride (Merck Ltd., Germany), Cobalt nitrate (Merck Ltd., Germany), Deionized water. Different cefixime suspensions and capsule were collected randomly at different pharmacies in Multan and Lahore Punjab, Pakistan.

Instruments

Spectrophotometer UV-Vis double beam UVD3500, Japan. pH meter (pH2100 OAWD35621), Germany, Analytical balance (ESJ200 Shenyang Longgten Electronic Co. Ltd), USA. Whatman filter paper No. 41, Germany.

Preparation of Cefixime Complexes with Cobalt Chloride (Method-A)

Cefixime stock solution (10ug/ml) was prepared by dissolving 10mg of Cefixime in 1000ml of methanol. Aliquot volumes of cefixime stock solution (10ug/ml) were transferred to calibrated flasks to prepare 0.1-0.6ug/ml analyte solution and 4 ml of 5% cobalt chloride solution was added to each flask and allowed to react at room temperature (25+-3degC) for 10 minutes, the contents of each flask were diluted to volume with methanol. The solution was scanned between 200nm - 400nm wave length to found l max, which was 256nm. Absorbance versus different cefixime concentrations was plotted at 256 nm. Methanol treated with cobalt chloride was considered as blank.

Preparation of Cefixime Complexes with Cobalt Nitrate (Method-B)

Various cefixime concentrations (0.1-1.5ug/ml) were prepared from stock solution (10ug/ml) by transferring stock solution to volumetric flasks. 4ml of 5% cobalt nitrate solution was added to each flask. After 10 minutes of reaction at room temperature, the contents of each flask were diluted with methanol. The solution was scanned between 200nm - 400nm wave length to found l max, which was 211 nm. Graph was plotted between cefixime concentrations and absorbance at 211nm. Cobalt nitrate added to methanol was taken as blank.

Procedure for Cefixime Capsules Analysis

Twenty capsules were selected randomly and their contents were taken in pestle and mortar, mixed thoroughly by soft mixing. To prepare stock solution (10ug/ml cefixime), accurately 1 mg powder of cefixime was transferred to 100 ml volumetric flask. 20 ml of methanol was added to the flask and sonicated for 20 min. The solution was filtered through whatman filter paper No. 41 and the volume was completed with methanol. From stock solution,0.4 ug/ml of cefixime was prepared by treating it with cobalt chloride and absorbance was measured at 256 nm. Similarly cobalt nitrate was treated with cefixime solution (0.4ug/ml) according to cobalt nitrate method and absorbance was measured at 211 nm. The concentration of cefixime in capsules was determined from their standard calibration graphs.

Procedure for Cefixime Suspension Analysis

A stock solution of 10ug/ml was prepared from a commercially available cefixime suspension (100mg/5ml). From stock solution, 0.4ug/ml solution was prepared by treating it with cobalt chloride and cobalt nitrate separately as mentioned above. The absorbance of the sample solution was recorded at256 nm and 211 nm respectively. The concentration of cefixime in solution was determined from their standard calibration graphs.

Validation of the Method

The methods were validated according to the international council of harmonization (ICH) guidance in terms of linearity, accuracy, precision, limits of quantization and selectivity.

Linearity

Linearity of the proposed methods was determined by analyzing the solutions of Cefixime with cobalt chloride and cobalt nitrate in the range of 0.1-0.6 ug/ml and 0.1-1.5 ug/ml respectively. The limit of detection (LOD) and limit of quantification (LOQ) was then established by evaluating the minimum level at which drug solution can be readily quantified with accuracy. LOD and LOQ were calculated according to the 3.3d/s and 10 d/s criteria, respectively, where d is the standard deviation of the response and s is the slope of the corresponding calibration curve.

Accuracy

Accuracy of the method was determined by performing recovery studies by standard addition method in which pre analyzed samples were taken and standard drug was spiked at three different levels i.e., 80%, 100% and 120%.

Precision

System precision was estimated from repeatability and reproducibility. The Intraday and interday precision of the method were confirmed by measuring absorbance of six replicate samples of cefixime salts three times in a day and also on two different days. Percentage relative standard deviation (% RSD) values should less than 2%.

Conclusion

Cefixime exhibited substantial amount of absorption in the UV region after formation of complexes with cobalt chloride/cobalt nitrate which can be used quantitatively for the estimation of cefixime in pharmaceutical raw material as well as in various dosage forms. All the statistical parameters along with recovery data confirm the reproducibility and accuracy of methods. During analysis no interference with the formulation excipients confirms the selectivity as well as specificity of proposed methods. The methods were validated for various other parameters as per ICH guidelines in which they were found to be within the acceptance criteria whereas the comparison of proposed methods with the existing procedures for all parameter showed it to be more sensitive. Hence the methods can be satisfactorily applied in quality control analysis of cefixime in pure as well as dosage forms.

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Author:Saeed-Ul-Hassan, Syed; Ansari, Muhammad Tayyab; Sadad, Shumila; Tariq, Imran; Mahmood, Zahid
Publication:Journal of the Chemical Society of Pakistan
Article Type:Report
Geographic Code:9PAKI
Date:Jun 30, 2013
Words:1819
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