SIMULTANEOUS ESTIMATION OF LINEZOLID AND CEFIXIME IN THEIR COMBINED DOSAGE FORM

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ABOUT AUTHORS:
Joshi HV*¹, Patel JK², Shah UA¹, Patel Kinjal^1
1Department of QA,
²Department of Pharmaceutics,
Nootan Pharmacy College, Visnagar, Gujarat, India
hirakjoshi@gmail.com

ABSTRACT
Simple, accurate, precise, reproducible, requiring no prior separation and economical procedures for simultaneous estimation of Linezolid (LIN) and Cefixime (CEF) in tablet dosage form have been developed. The method is simultaneous equation method; in this method 257.0 nm and 288.0 nm were selected respectively for LIN and CEF to measure the absorbance of both the drugs at mentioned wavelengths. Both the drugs show linearity at 10-50 μg/mL, the range was selected by studying their ratio present in combined formulation. Recovery studies range from >99.35% for CEF and >99.23% for LIN in mentioned analytical method i.e. simultaneous equation method. The proposed methods are recommended for routine analysis since it is rapid, simple, accurate and also sensitive and specific (no heating and no organic solvent extraction is required).

REFERENCE ID: PHARMATUTOR-ART-2309

INTRODUCTION
Cefuroxime is chemically (6R,7R)-3-carbamoyloxymethyl-7-[(Z)-2-(2-furyl)-2-(methoxyimino)acetamido]-ceph-3-em-4-carboxylic acid. Cefuroxime is official in Indian pharmacopoeia. It is the first of the series of alpha methoxyiminoacyl substituted cephalosporins that constitute most of the third generation agents available for clinical use. It is active against some beta lactamase strains that are resistant to cefamandole.

Linezolid (LIN) is a synthetic antibacterial agent of the oxazolidinone class of antibiotics. Linezolid is chemically N-{[(5S)-3-[3-fluoro-4- (morpholin-4-yl) phenyl]-2-oxo-1, 3- oxazolidin-5-yl] methyl} acetamide. Clinically used for the treatment of infections caused by multi-resistant bacteria including streptococcus and methicillin resistant Staphylococcus aureus (MRSA). The drug works by inhibiting the initiation of bacterial protein synthesis.

Both the drugs are marketed as combined dose tablet formulation in the ratio of 200:600 mg CEF: LNZ. Literature survey reveals that Cefixime can be estimated by Spectrophotometrically^(1-4), and by HPLC ^(2,3)  individually or with other drugs in bulk drugs and in human plasma, while Linezolid can be estimated by Spectrophotometrically ^[5,7], HPLC ^[8,9]and determination of Linizolid in plasma^(9,10) in combination with other drugs. However, there is no analytical method reported for the estimation of CEF and LIN in a combined dosage formulation.

MATERIALS AND REAGENTS:
A Shimadzu UV/Visible spectrophotometer (Model: UV1700) was employed with spectral bandwidth of 2nm and wavelength accuracy of ± 0.5 nm with automatic wavelength correction with a pair of 10mm quartz cells. Cefixime (Sun Pharmaceuticals Ltd.)  Linezolid (Torrent Pharmaceuticals) and Methanol – AR grade (Qualigens Fine Chemicals, Mumbai) were used in the study.

EXPERIMENTAL PROCEDURE
Two wavelengths selected for the method are 257.0 nm and 288.0 nm that are Absorption maxima respective for LIN and CEF methanol. The stock solutions of both the drugs were further diluted separately with methanol to get a series of standard solutions of 10-50 µg/mLfor both the drugs concentrations. The absorbances were measured at the selected wavelengths and absorptivities (A1%,1cm) for both the drugs were determined as mean of six independent determinations. Concentrations in the sample were obtained by using following equations.

Cx = (A₂ay₁-A₁ay₂)/(ax₂ay₁-ax₁ay₂)

Cy = (A₁ax₂-A₂ax₁)/(ax₂ay₁-ax₁ay₂)

Where A₁ and A₂ are absorbances of mixture at 257.0 nm and 288.0 nm respectively, ax₁ and ax₂ are absorptivities of CEF at λ₁ and λ₂ respectively and ay₁ and ay₂ are absorptivities of LIN at at λ₁ and λ₂ respectively. Cx and Cy are concentration of CEF and LIN respectively.

Analysis of marketed tablet formulation:
Tablet sample solution was made as per the method described in Method – I and solution was diluted to get a final concentration equivalent to 10 μg/ml of CEF and 30 μg/ml of LIN (n=6) and from the overlain spectra the absorbances were measured at 257.0 nm for LIN and 288.0 nm for CEF in spectrophotometric mode of an instrument. Amount of drug present in the sample solution was obtained from the simultaneous equation.

The results of analysis and statistical validation for the marketed tablet formulation are reported in Table-1 and Table-2 respectively. The results of recovery studies conducted by the addition of different amounts of pure drugs at 80%, 100% and 120% levels to a tablet solution were found to be satisfactory and are given in the Table-3.

RESULT AND DISCCUSION:
The simultaneous equation method, also called as verdict’s method, employs the absorption  at two selected wavelengths and can be employed for the routine analysis of the two drugs in the combined dosage forms using simple instrument which requires more accuracy.  The method is used to eliminate the spectral interference from one of the two drugs as the wavelength for estimation of the other drug. This method requires spectral data processing and hence can be performed only on recording spectrophotometers with such facilities.

The amount found from the proposed methods was in good agreement with the label claim of the formulation. Also the value of standard deviation and coefficient of variation calculated were satisfactorily low, indicating the suitability of the proposed methods for the routine estimation of tablet dosage forms.

CONCLUSION
From above it is concluded that the simple, economical, precise and accurate spectrophotometric simultaneous equation method (Verdicts Method) had been developed for simultaneous determination of Cefixime and Linezolid in bulk and tablet formulation was developed and validated as per ICH guidelines. Thus it can be used as IPQC test and for routine simultaneous determination of Cefixime and Linezolid in tablet dosage form. The method had been validated by different parameters like accuracy, precision; Linearity, LOD and LOQ which was found to be with in mentioned limit as per ICH guidelines.

TABLE

1: ANALYSIS OF TABLET FORMULATION

T1= LCZ-2 (IIFA pharmaceuticals India Ltd)
T2= LINCEF (Alkem Pharmaceuticals)

TABLE 2: STATISTICAL VALIDATION OF TABLET FORMULATION

TABLE 3: STATISTICAL VALIDATION OF RECOVERY STUDIES

CEF is cefuxime and LIN is Linezolid

* Denotes average of six estimation.

Acknowledgements
Author wishes to thanks to Nootan Pharmacy College, Visnagar for providing the Instrumental and Chemicals facility. Authors are also thankful to Sun Pharmaceuticals PVT LTD, Baroda and Torrent Pharmaceuticals LTD, Ahmedabad for providing the gift samples of Cefixime and Linezolid respectively.

REFERENCES:
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