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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 Kinjal1
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

PharmaTutor (ISSN: 2347 - 7881)

Volume 3, Issue 2

Received On: 21/11/2014; Accepted On: 02/12/2014; Published On: 01/02/2015

How to cite this article: HV Joshi, JK Patel, UA Shah, K Patel; Simultaneous Estimation of Linezolid and Cefixime in their Combined Dosage Form; PharmaTutor; 2015; 3(2); 48-52

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

Label claim  (mg/tab)

Amount Found* 

(mg/tab)

Label claim

(%)

T1

T2

T1

T2

T1

T2

CEF

LIN

CEF

LIN

CEF

LIN

CEF

LIN

CEF

LIN

CEF

LIN

200

600

200

600

197

592

203

911

98.51

98.66

101.49

101.83

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

TABLE 2: STATISTICAL VALIDATION OF TABLET FORMULATION

Standard Deviation

% coefficient of variation

Standard error

T1

T2

T1

T2

T1

T2

CEF

LIN

CEF

LIN

CEF

LIN

CEF

LIN

CEF

LIN

CEF

LIN

0.115

0.1236

0.1241

0.0562

0.414

0.36

0.145

0.86

0.021

0.023

0.036

0.014

TABLE 3: STATISTICAL VALIDATION OF RECOVERY STUDIES

Type of Recovery in %

Mean

±S D*

Coefficient of variation*

Standard Error*

T1

T2

T1

T2


T1

T2

CEF

LIN

CEF

LIN

CEF

LIN

CEF

BEN

CEF

LIN

CEF

LIN

80

98.23

±0.09

99.54

±0.13

100.38

±0.83

98.50

±0.43

99.26
±0.21

99.54

±0.25

101.83
±0.52

99.50

±0.43

99.13
±0.62

99.86

±0.43

99.36

±0.14

101.25

±0.41

100

99.87

±0.21

99.80

±0.15

98.46

±0.77

101.03

±0.37

99.82
±0.19

100.52

±0.25

99.76
±0.31

100.97

±0.37

99.26
±0.21

98.65

±0.37

99.86

±0.17

98.17

±0.17

120

99.10

±0.21

100.07

±0.21

99.61

±1.15

100.09
±0.43

100.21
±0.21

101.06

±0.19

99.16

±0.27

100.10

±0.12

99.36
±0.27

100.10

±0.2179

100.08

±0.21

101.09

±0.11

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:
1. Vishal S, Hasumati R., Development and validation of derivative spectroscopic method for simultaneous estimation of Cefixime-trihydrate and Azithromyc-indihydrate in combined dosage form. International Journal of Pharmaceutical Sciences And Research, 2012, 3(6), 1753-1760.
2. Rolando GH, Lauro NP, Laritza SM, Miguel LL. Reversed phase high performance liquid chromatographic determination of Cefixime in bulk drugs. Journal of Liquid Chromatography & Related Technologies, 2001, 24(15), 2315-2324.
3. Pawar S. J, Kale A.P, Amrutkar M.P, Jagade J.J, Pore N.S and Bhosale A.V., HPTLC Estimation of Cefixime and Cloxacillin in Tablet Dosage Form. Asian J. Research Chem, 2010, 3(2), 299-301.
4. Patel R.K., Parmar R.R., Patel V.M, Shah D.A., Method devlopment and validation of Cefixime and Moxifloxacin in pharmaceutical dosage form by UV spectrophotometric method. International journal of pharmaceuticai research, 2012,1(2), 81-93.
5. Patel S.A., Determination of Linezolid in pharmaceutical dosage forms by liquid chromatography and ultraviolet spectroscopy, 2007, Vol 5, 1272-1277.
6. Ritchie E.M. HPLC-UV Method for the Determination of Linezolid Using a Core Enhanced Technology. Accucore Column, 2011, 245-249.
7. Raju T.  S, Kutty O.V, Ganesh V, Swamy P. Y. A validated stability-indicating LC method for the separation of enantiomer and potential impurities of Linezolid using polar organic mode. Journal of Pharmaceutical Analysis, 2012, 2(4), 272-278
8. Toutain J , Boselli E, Djabarouti S, Allaouchiche B, Xuereb F, Bernadou J , Ba B, Saux M.C , Breilh D. Determination of Linezolid in plasma and broncho alveolar lavage by HPLC with UV detection using a fully automated extraction method. Journal of Chromatography B, 2004, 813(1-2),145-50.
9. Traunmüller F , Mauric O, Popovic M and Joukhadar   C. Determination of the Antibiotic Linezolid in Low Plasma Volumes by High-Performance Liquid Chromatography. Journal of Chromatographic Science, 2012, 48 (5), 325-327.
10. Mohapatra S, Kumar BV, Anwar M , Warsi  MH,  Akhter S. validated stability indicating RP-HPLC  method for the estimation of Linezolid in a pharmaceutical dosage form. Journal of liquid chromatography & related technologies. 2011, 34(18), 2185-2195.

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