Abstract
A reversed-phase high-performance liquid chromatography (RP-HPLC) method for the rapid and accurate quantification of zidovudine (AZT) in sustained release tablets during stability testing was developed. A Waters RP-18 XTerraTM® column, using a water:methanol (80:20, v/v%) mobile phase at a flow rate of 1.0 ml min−1, and UV detection at 266 nm, was employed. The method of validation parameters indicate a linear range of between 40.0 to 220.0 μg ml−1 with an LOQ of 1.985 μg ml−1 and an LOD of 0.655 μg ml−1 for the analyte. The degradation products of AZT were isolated and characterized for the first time. There was a very little decline of antiviral by heat, and AZT did not completely degrade either by acid or alkaline hydrolysis. On the other hand, oxidation caused a higher degradation stress in the drug. Finally, the degradation products resulting from stress studies were not found to interfere with the detection of antiviral, which is an advantage of the presently proposed method.
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N. A. Ochekpe, N. C. Ngwuluka, H. Owolayo, and T. Fashedemi, Diss. Tecnol., 2006, November, 12.
G. Ramachandran, A. K. Hemanthkumar, V. Kumaraswami, and S. J. Swaminathan, J. Chromatogr., B, 2006, 843, 339.
M. A. Quevedo, S. R. Ribone, G. N. Moroni, and M. C. Briñón, Bioorg. Med. Chem., 2008, 16, 2779.
C. H. R. Serra, E. E. M. Koono, E. K. Kano, S. G. Schramm, Y. P. Armando, and V. Porta, Clin. Ther., 2008, 30, 902.
B. Uslu and S. A. Özkan, Anal. Chim. Acta, 2002, 466, 175.
The United States Pharmacopeia, USP 31/NF 26, 2008, ed. Rockville, United States Pharmacopeia Convention, Inc., MD, 3553.
A. Kuksal, A. K. Tiwary, N. K. Jain, and S. Jain, AAPS PharmSciTech., 2006, 7, E1–E9.
M. Pendela, E. Van Gyseghem, G. Van den Mooter, L. Baert, J. Rosier, J. Hoogmartens, and E. Adams, J. Pharm. Biomed. Anal., 2009, 49, 508.
Eurachem Working Group, The Fitness for Purpose of Analytical Methods: A Laboratory Guide to Method Validation and Related Topics, 1998, http://www.eurachem.org/guides/pdf/valid.pdf.
FDA (Food and Drug Administration), Guidance for Industry: Analytical Procedures and Methods Validation, Center for Drug Evaluation and Research, 2000, http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm122858.pdf.
ICH Q2(R1), Validation of Analytical Procedures: Text and Methodology, International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use, 2005, http://www.ich.org/LOB/media/MEDIA417.pdf.
NATA Technical Note 17, Guidelines for the Validation and Verification of Chemical Test Methods, 2009, http://www.nata.com.au/publications/category/9-nata-technical-notes.
J. Ermer, J. Pharm. Biomed. Anal., 2001, 24, 755.
J. Ermer and H. J. Ploss, J. Pharm. Biomed. Anal., 2005, 37, 859.
Ph. Hubert, J. J. Nguyen-Huu, B. Boulanger, E. Chapuzet, P. Chiap, N. Cohen, P. A. Compagnon, W. Dewé, M. Feinberg, M. Lallier, M. Laurentie, N. Mercier, G. Muzard, C. Nivet, L. Valat, and E. Rozet, J. Pharm. Biomed. Anal., 2007, 45, 70.
Ph. Hubert, J. J. Nguyen-Huu, B. Boulanger, E. Chapuzet, N. Cohen, P. A. Compagnon, W. Dewé, M. Feinberg, M. Laurentie, N. Mercier, G. Muzard, L. Valat, and E. Rozet, J. Pharm. Biomed. Anal., 2007, 45, 82.
M. Bakshi and S. Saranjit, J. Pharm. Biomed. Anal., 2002, 28, 1011.
ICH Q1A(R2), Stability Testing of New Drug Substances and Products, International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use, 2003, http://www.ich.org/LOB/media/MEDIA419.pdf.
ICH Q1B, Stability Testing: Photostability Testing of New Drug Substances and Products, International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use, 2005, http://www.ich.org/LOB/media/MEDIA412.pdf.
K. C. Waterman and R. C. Adami, Int. J. Pharm., 2005, 293, 101.
W. Aman and K. Thoma, Int. J. Pharm., 2002, 243, 33.
L. Maggi, E. O. Machiste, E. Fasani, A. Albini, L. Segale, and U. Conte, Eur. J. Pharm. Biopharm., 2003, 55, 99.
J. Karpińska, A. Sokól, and M. Skoczyla, Spectrochim. Acta, Part A, 2008, 71, 1562.
SPSS Statistics for Windows Ver. 16.0, Statistical Software, Inc., 2007.
A. Dunge, A. K. Chakraborti, and S. Singh, J. Pharm. Biomed. Anal., 2004, 35, 965.
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dos Santos, J.V., de Carvalho, L.A.E.B. & Pina, M.E. Development and Validation of a RP-HPLC Method for the Determination of Zidovudine and Its Related Substances in Sustained-release Tablets. ANAL. SCI. 27, 283–289 (2011). https://doi.org/10.2116/analsci.27.283
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DOI: https://doi.org/10.2116/analsci.27.283