Method Development and Validation for the Determination of Cefixime in Pure and Commercial Dosage Forms by Specrophotometry
A simple, accurate and precise direct spectrophotometric method has been developed for the determination of cefixime in tablets and capsules. The method is based on the reaction of cefixime with a mixture of potassium iodide and potassium iodate to form yellow coloured product in ethanol-distilled water medium at room temperature which absorbed maximally at 352 nm. The factors affecting the reaction product were carefully studied and optimized. The validation parameters based on International Conference on Harmonisation (ICH, USA) guidelines were followed. The effect of common excipients used as additives has been tested and the tolerance limit was calculated for the determination of cefixime. Beer’s law is obeyed in the concentration range of 4 – 24 ug mL-1 with apparent molar absorptivity of 1.52 × 104 L mol-1cm-1 and Sandell’s sensitivity of 0.033 ug/cm2/ 0.001 absorbance unit. The limits of detection and quantitation for the proposed method are 0.32 and 1.06 ug mL-1, respectively. The proposed method has been successfully applied for the determination of cefixime in pharmaceutical formulations. The results obtained by the proposed method were statistically compared with the reference method using t- and F- values and found no significant difference between the two methods. The proposed method can be used as an alternate method for routine quality control analysis of cefixime in pharmaceutical formulations.
[1] British Pharmacopoeia, vol. I, Her Majesty Stationary Office, London,
UK, 2009, p. 1139.
[2] F. Meng, X. Chen, Y. Zeng and D. Zhong, “Sensitive liquid
chromatography-tandem mass spectrometry method for the
determination of cefixime in human plasma: application to a
pharmacokinetic study,” J. Chromatogr. B: Analyt. Technol. Biomed.
Life Sci., vol. 819, p. 277, 2005.
[3] K. A. Raj, D. Yadav, D. Yadav, C. Prabu and S. Manikantan,
“Determination of cefixime trihydrate and cefuroxime axetil in bulk
drug and pharmaceutical dosage forms by HPLC,” Int. J. Chemtech.
Res., vol. 2, p. 334, 2010.
[4] D. Zendelovska, T. Stafilov and P. Miloševski, “High-Performance
liquid chromatographic method for determination of cefixime and
cefotaxime in human plasma,” Bull. Chem. Technol. Macedonia, vol. 22,
pp. 39-45, 2003.
[5] E. H. K. Adam, A. E. M. Saeed and I. E. Barakat, “Development and
validation of a high performance liquid chromatography method for
determination of cefixime trihydrate and its degraded products formed
under stress condition of UV light,” Int. J. Pharm. Sci. Res. vol. 3, p.
469, 2012.
[6] K. Kathiresan, R. Murugan. M. S. Hameed, K. G. Inimai and T.
Kanyadhara, “Analytical method development and validation of
cefixime and dicloxacillin tablets by RP-HPLC,” Rasayan J. Chem., vol.
2, pp. 588, 2010.
[7] K. S. Khandagle, S. V. Gandhi, P. B. Deshpande, A. N. Kale and P. R.
Deshmukh, “High performance thin layer chromatographic
determination of cefixime and ofloxacin in combined tablet dosage
form,” J. Chem. Pharm. Res., vol. 2, p. 92, 2012.
[8] M. M. Deshpandea, V. S. Kastureb and S. A, Gosavib, “Application of
HPLC and HPTLC for the simultaneous determination of cefixime
trihydrate and ambroxol hydrochloride in pharmaceutical dosage form,”
Eurasian J. Anal. Chem. vol. 5, p. 227, 2010.
[9] V. Shah and H. Raj, “Development and validation of derivative
spectroscopic method for simultaneous estimation of cefixime trihydrate
and azithromycin dihydrate in combined dosage form,” Int. J. Pharm.
Sci. Res. vol. 3, p. 1753, 2012.
[10] R. Jain, V. K. Gupta and N. Jadon, “Voltammetric determination of
cefixime in pharmaceuticals and biological fluids,” Anal. Biochem. vol.
407, p. 79, 2010.
[11] K. A. Raj, “Determination of cefixime trihydrate and cefuroxime axetil
in bulk drug and pharmaceutical dosage forms by electrophoretic
method,” Int. J. ChemTech. Res., vol. 2, p. 337, 2010.
[12] A. R. Solangi, S. Q. Memon, M. Y. Khuhawar, M. I. Bhanger,
“Quantitative analysis of eight cephalosporin antibiotics in
pharmaceutical products and urine by capillary zone electrophoresis,”
Acta Chromatographica vol. 19 pp. 81-96, 2007.
[13] S. N. H. Azmi, B. Iqbal, N. S. H. Al-Humaimia, I. R. S. Al-Salmania, N.
A. S. Al-Ghafria, N. Rahman, “Quantitative analysis of cefixime via
complexation with palladium(II) in pharmaceutical formulations by
spectrophotometry,” J. Pharm. Anal., vol. 3, pp. 248-256, 2013.
[14] G. A. Saleh, H. F. Askal, I. A, Darwish, A. -N. A. El-Shorbagi,
“Spectroscopic analytical study for the charge-transfer of certain
cephalosporins with chloranilic acid,” Anal. Sci. vol. 19 pp. 281-287,
2003.
[15] E. Y. Frag, A. B. Farag G. G. Mohamed, E. B. Yussof, “Development
and validation of spectrophotometric and HPLC methods for the
determination of cefixime in capsule and suspension,” Insight
Pharmaceutical Sciences, vol. 2, pp. 8-16, 2012.
[16] D. Agbaba, S. Eric, K. Karljikovic-Rajic, S. Vladimirov, D. Zivanov-
Stakic, “Spectrophotometric determination of certain cephalosporins
using ferrihydroxamate method,” Spectroscopy Letters vol. 30, p. 309,
1997.
[17] B. S. Virupaxappa1, K. H. Shivaprasad, M. S. Latha, “A simple method
for the spectrophotometric determination of cefixime in
pharmaceuticals,” Asian J. Res. Chem. vol. 4, 1257, 2011.
[18] P. B. Shah and K. Pundarikakshudu, “Spectrophotometric, difference
spectroscopic, and high-performance liquid chromatographic methods
for the determination of cefixime in pharmaceutical formulations, ” J.
AOAC Int., vol. 89, p. 987, 2006.
[19] S. I. Pasha, A. S. Kumar, K. Sravanthi,G. Srinika and V. Nikhila, “New
visible spectrophotometric method for the determination of cefixime
trihydrate in pharmaceutical formulations,” Orient J. Chem. vol. 28, p.
571, 2012.
[20] A. Kumar, L. Kishore, A. Nair and N. Kaur, “Kinetic
spectrophotometric method for the estimation of cefixime in
pharmaceutical formulations”, Der Pharma Chemica vol 3 pp. 279-291,
2011.
[21] J. Shah, M. R. Jan, S. Shah, and Inayatullah, “Spectrofluorimetric
method for determination and validation of cefixime in pharmaceutical
preparations through derivatization with 2-cyanoacetamide,” J.
Fluoresc. 21, 579, 2011.
[22] D. A. C. Czegan and D. K. Hoover, “UV-visible spectrometers: versatile
instruments across the chemistry curriculum,” J. Chem. Educ. vol. 89, p.
304, 2012.
[23] International Conference on Harmonisation, Food and Drug
Administration, ICH Harmonised Tripartite Guideline – Text on
Validation of Analytical Procedures. Rockville, MD, USA. Fed. Regist.
1995, 60, p. 11260.
[24] C. Hartmann, J. Smeyers-Verbeke, W. Pinninckx, Y. V. Heyden, P.
Vankeerberghen, and D. L. Massart, “Reappraisal of hypothesis testing
for method validation: detection of systematic error by comparing the
means of two methods or of two laboratories,” Anal. Chem. 67, p. 4491,
1995.
[25] F. Feigl, Preliminary (Exploratory tests). In: Spot tests in organic
analysis. 6th ed., Elsevier publishing company, Amsterdam. 1960, pp.
117–118.
[26] V. V. Nalimov, The Application of Mathematical Statistics to Chemical
Analysis, Pergamon Press, Oxford, 1963. p. 167.
[27] J. C. Miller and J. N. Miller, “Errors in instrumental analysis;
regression and correlation,” In: Statistics for analytical chemistry, Third
edition, Ellis Horwood and Prentice Hall, England, 1993, p. 119.
[28] J. Mendham, R. C. Denney, J. D. Barnes, M. Thomas, “Statistics:
Introduction to Chemometrics,” In: Vogel’s Textbook of Quantitative
Chemical Analysis, 6th ed., Pearson Education, Singapore. 2002, p. 137.
[1] British Pharmacopoeia, vol. I, Her Majesty Stationary Office, London,
UK, 2009, p. 1139.
[2] F. Meng, X. Chen, Y. Zeng and D. Zhong, “Sensitive liquid
chromatography-tandem mass spectrometry method for the
determination of cefixime in human plasma: application to a
pharmacokinetic study,” J. Chromatogr. B: Analyt. Technol. Biomed.
Life Sci., vol. 819, p. 277, 2005.
[3] K. A. Raj, D. Yadav, D. Yadav, C. Prabu and S. Manikantan,
“Determination of cefixime trihydrate and cefuroxime axetil in bulk
drug and pharmaceutical dosage forms by HPLC,” Int. J. Chemtech.
Res., vol. 2, p. 334, 2010.
[4] D. Zendelovska, T. Stafilov and P. Miloševski, “High-Performance
liquid chromatographic method for determination of cefixime and
cefotaxime in human plasma,” Bull. Chem. Technol. Macedonia, vol. 22,
pp. 39-45, 2003.
[5] E. H. K. Adam, A. E. M. Saeed and I. E. Barakat, “Development and
validation of a high performance liquid chromatography method for
determination of cefixime trihydrate and its degraded products formed
under stress condition of UV light,” Int. J. Pharm. Sci. Res. vol. 3, p.
469, 2012.
[6] K. Kathiresan, R. Murugan. M. S. Hameed, K. G. Inimai and T.
Kanyadhara, “Analytical method development and validation of
cefixime and dicloxacillin tablets by RP-HPLC,” Rasayan J. Chem., vol.
2, pp. 588, 2010.
[7] K. S. Khandagle, S. V. Gandhi, P. B. Deshpande, A. N. Kale and P. R.
Deshmukh, “High performance thin layer chromatographic
determination of cefixime and ofloxacin in combined tablet dosage
form,” J. Chem. Pharm. Res., vol. 2, p. 92, 2012.
[8] M. M. Deshpandea, V. S. Kastureb and S. A, Gosavib, “Application of
HPLC and HPTLC for the simultaneous determination of cefixime
trihydrate and ambroxol hydrochloride in pharmaceutical dosage form,”
Eurasian J. Anal. Chem. vol. 5, p. 227, 2010.
[9] V. Shah and H. Raj, “Development and validation of derivative
spectroscopic method for simultaneous estimation of cefixime trihydrate
and azithromycin dihydrate in combined dosage form,” Int. J. Pharm.
Sci. Res. vol. 3, p. 1753, 2012.
[10] R. Jain, V. K. Gupta and N. Jadon, “Voltammetric determination of
cefixime in pharmaceuticals and biological fluids,” Anal. Biochem. vol.
407, p. 79, 2010.
[11] K. A. Raj, “Determination of cefixime trihydrate and cefuroxime axetil
in bulk drug and pharmaceutical dosage forms by electrophoretic
method,” Int. J. ChemTech. Res., vol. 2, p. 337, 2010.
[12] A. R. Solangi, S. Q. Memon, M. Y. Khuhawar, M. I. Bhanger,
“Quantitative analysis of eight cephalosporin antibiotics in
pharmaceutical products and urine by capillary zone electrophoresis,”
Acta Chromatographica vol. 19 pp. 81-96, 2007.
[13] S. N. H. Azmi, B. Iqbal, N. S. H. Al-Humaimia, I. R. S. Al-Salmania, N.
A. S. Al-Ghafria, N. Rahman, “Quantitative analysis of cefixime via
complexation with palladium(II) in pharmaceutical formulations by
spectrophotometry,” J. Pharm. Anal., vol. 3, pp. 248-256, 2013.
[14] G. A. Saleh, H. F. Askal, I. A, Darwish, A. -N. A. El-Shorbagi,
“Spectroscopic analytical study for the charge-transfer of certain
cephalosporins with chloranilic acid,” Anal. Sci. vol. 19 pp. 281-287,
2003.
[15] E. Y. Frag, A. B. Farag G. G. Mohamed, E. B. Yussof, “Development
and validation of spectrophotometric and HPLC methods for the
determination of cefixime in capsule and suspension,” Insight
Pharmaceutical Sciences, vol. 2, pp. 8-16, 2012.
[16] D. Agbaba, S. Eric, K. Karljikovic-Rajic, S. Vladimirov, D. Zivanov-
Stakic, “Spectrophotometric determination of certain cephalosporins
using ferrihydroxamate method,” Spectroscopy Letters vol. 30, p. 309,
1997.
[17] B. S. Virupaxappa1, K. H. Shivaprasad, M. S. Latha, “A simple method
for the spectrophotometric determination of cefixime in
pharmaceuticals,” Asian J. Res. Chem. vol. 4, 1257, 2011.
[18] P. B. Shah and K. Pundarikakshudu, “Spectrophotometric, difference
spectroscopic, and high-performance liquid chromatographic methods
for the determination of cefixime in pharmaceutical formulations, ” J.
AOAC Int., vol. 89, p. 987, 2006.
[19] S. I. Pasha, A. S. Kumar, K. Sravanthi,G. Srinika and V. Nikhila, “New
visible spectrophotometric method for the determination of cefixime
trihydrate in pharmaceutical formulations,” Orient J. Chem. vol. 28, p.
571, 2012.
[20] A. Kumar, L. Kishore, A. Nair and N. Kaur, “Kinetic
spectrophotometric method for the estimation of cefixime in
pharmaceutical formulations”, Der Pharma Chemica vol 3 pp. 279-291,
2011.
[21] J. Shah, M. R. Jan, S. Shah, and Inayatullah, “Spectrofluorimetric
method for determination and validation of cefixime in pharmaceutical
preparations through derivatization with 2-cyanoacetamide,” J.
Fluoresc. 21, 579, 2011.
[22] D. A. C. Czegan and D. K. Hoover, “UV-visible spectrometers: versatile
instruments across the chemistry curriculum,” J. Chem. Educ. vol. 89, p.
304, 2012.
[23] International Conference on Harmonisation, Food and Drug
Administration, ICH Harmonised Tripartite Guideline – Text on
Validation of Analytical Procedures. Rockville, MD, USA. Fed. Regist.
1995, 60, p. 11260.
[24] C. Hartmann, J. Smeyers-Verbeke, W. Pinninckx, Y. V. Heyden, P.
Vankeerberghen, and D. L. Massart, “Reappraisal of hypothesis testing
for method validation: detection of systematic error by comparing the
means of two methods or of two laboratories,” Anal. Chem. 67, p. 4491,
1995.
[25] F. Feigl, Preliminary (Exploratory tests). In: Spot tests in organic
analysis. 6th ed., Elsevier publishing company, Amsterdam. 1960, pp.
117–118.
[26] V. V. Nalimov, The Application of Mathematical Statistics to Chemical
Analysis, Pergamon Press, Oxford, 1963. p. 167.
[27] J. C. Miller and J. N. Miller, “Errors in instrumental analysis;
regression and correlation,” In: Statistics for analytical chemistry, Third
edition, Ellis Horwood and Prentice Hall, England, 1993, p. 119.
[28] J. Mendham, R. C. Denney, J. D. Barnes, M. Thomas, “Statistics:
Introduction to Chemometrics,” In: Vogel’s Textbook of Quantitative
Chemical Analysis, 6th ed., Pearson Education, Singapore. 2002, p. 137.
@article{"International Journal of Chemical, Materials and Biomolecular Sciences:68195", author = "S. N. H. Azmi and B. Iqbal and J. K. Al Mamari and K. A. Al Hattali and W. N. Al Hadhrami", title = "Method Development and Validation for the Determination of Cefixime in Pure and Commercial Dosage Forms by Specrophotometry", abstract = "A simple, accurate and precise direct spectrophotometric method has been developed for the determination of cefixime in tablets and capsules. The method is based on the reaction of cefixime with a mixture of potassium iodide and potassium iodate to form yellow coloured product in ethanol-distilled water medium at room temperature which absorbed maximally at 352 nm. The factors affecting the reaction product were carefully studied and optimized. The validation parameters based on International Conference on Harmonisation (ICH, USA) guidelines were followed. The effect of common excipients used as additives has been tested and the tolerance limit was calculated for the determination of cefixime. Beer’s law is obeyed in the concentration range of 4 – 24 ug mL-1 with apparent molar absorptivity of 1.52 × 104 L mol-1cm-1 and Sandell’s sensitivity of 0.033 ug/cm2/ 0.001 absorbance unit. The limits of detection and quantitation for the proposed method are 0.32 and 1.06 ug mL-1, respectively. The proposed method has been successfully applied for the determination of cefixime in pharmaceutical formulations. The results obtained by the proposed method were statistically compared with the reference method using t- and F- values and found no significant difference between the two methods. The proposed method can be used as an alternate method for routine quality control analysis of cefixime in pharmaceutical formulations.
", keywords = "Spectrophotometry, cefixime, validation,
pharmaceutical formulations.", volume = "8", number = "6", pages = "595-7", }
