Simultaneous Monitoring of Febuxostat and Uric Acid in Human Serum Samples Using the Direct Square-Wave Voltammetric Method

Author(s): Biljana Nigović*, Jakov Vlak

Journal Name: Current Analytical Chemistry

Volume 15 , Issue 6 , 2019

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Graphical Abstract:


Background: High uric acid serum level, hyperuricemia, is now associated with many diseases such as gout, chronic kidney disease, hypertension, coronary artery disease and diabetes. Febuxostat is a novel selective xanthine oxidase inhibitor approved for the treatment of hyperuricemia.

Objective: The aim of this study was to develop a first analytical method for the simultaneous determination of febuxostat and uric acid.

Methods: An unmodified boron-doped diamond electrode provided concurrent quantitation of drug at low levels and uric acid, which has clinical significance in the diagnosis and therapy of hyperuricemia, at relatively high concentrations. The direct square-wave voltammetric method was applied to the analysis of both analytes in human serum samples.

Results: Under the optimized conditions, the linear response of peak current on febuxostat concentration was achieved in the range from 7.5 × 10-7 to 3 × 10-5 M, while uric acid showed two linear ranges of 5 × 10-6 - 5 × 10-5 M and 5 × 10-5 - 2 × 10-4 M. The method was successfully utilised for quantification of both analytes in human serum samples. Good recoveries were obtained without interference from common inorganic cations and anions as well as glucose, dopamine, ascorbic and folic acids at concentrations expected in physiological conditions.

Conclusion: The great benefits of developed method are fast analysis (only 7.5 s for run), low cost and simplicity of performance.

Keywords: Febuxostat, human serum, hyperuricemia, simultaneous determination, uric acid, voltammetry.

Ojha, R.; Singh, J.; Ojha, A.; Singh, H.; Sharma, S.; Nepali, K. An updated patent review: Xanthine oxidase inhibitors for the treatment of hyperuricemia and gout (2011-2015). Expert Opin. Ther. Pat., 2017, 27, 311-345.
Hahn, K.; Kanbay, M.; Lanaspa, M.A.; Johnson, R.J.; Ahsan Ejaz, A. Serum uric acid and acute kidney injury: A mini review. J. Adv. Res., 2017, 8, 529-536.
Dalbeth, N.; Merriman, T.R.; Stamp, L.K. Gout. Lancet, 2016, 388, 2039-2052.
Ye, P.; Yang, S.; Zhang, W.; Lv, Q.; Cheng, Q.; Mei, M.; Luo, T.; Liu, L.; Chen, S.; Li, Q. Efficacy and tolerability of febuxostat in hyperuricemic patients with or without gout: A systematic review and meta-analysis. Clin. Ther., 2013, 35, 180-189.
Grewal, H.K.; Martinez, J.R.; Espinoza, L.R. Febuxostat: Drug review and update. Expert Opin. Drug Metab. Toxicol., 2014, 10, 747-758.
Frampton, J.E. Febuxostat: A review of its use in the treatment of hyperuricaemia in patients with gout. Drugs, 2015, 75, 427-738.
Kishimoto, K.; Kobayashi, R.; Hori, D.; Sano, H.; Suzuki, D.; Kobayashi, K. Febuxostat as a prophylaxis for tumor lysis syndrome in children with hematological malignancies. Anticancer Res., 2017, 37, 5845-5849.
Wu, Y.L.; Mao, Z.S.; Liu, Y.P.; Wang, X.; Di, X. Simultaneous determination of febuxostat and its three active metabolites in human plasma by liquid chromatography-tandem mass spectrometry and its application to a pharmacokinetic study in Chinese healthy volunteers. J. Pharm. Biomed. Anal., 2015, 114, 216-221.
Choudhury, H.; Gorain, B.; Das, A.; Ghosh, B.; Pal, T. Development and validation of a sensitive HPLC-MS/MS-ESI method for determination of febuxostat: Application to pharmacokinetic study. Curr. Anal. Chem., 2014, 10, 528-536.
Tandel, D.; Shah, P.; Patel, K.; Thakkar, V.; Patel, K.; Gandhi, T. Salting-out assisted liquid-liquid extraction for quantification of febuxostat in plasma using RP-HPLC and its pharmacokinetic application. J. Chromatogr. Sci., 2016, 54, 1827-1833.
Mohamed, A-M.I.; Omar, M.A.; Derayea, S.M.; Hammad, M.A.; Mohamed, A.A. Innovative thin-layer chromatographic method combined with fluorescence detection for specific determination of febuxostat: Application in biological fluids. Talanta, 2018, 176, 318-328.
Sivasankaran, U.; Thomas, A.; Jose, A.R.; Girish Kumar, K. Poly(bromophenol blue)-gold nanoparticle composite: An efficient electrochemical sensing platform for uric acid. J. Electrochem. Soc., 2017, 164, B292-B297.
Movlaee, K.; Norouzi, P.; Beitollahi, H.; Rezapour, M.; Larijani, B. Highly selective differential pulse voltammetric determination of uric acid using modified glassy carbon electrode. Int. J. Electrochem. Sci., 2017, 12, 3241-3251.
Zhang, K.; Zhang, N.; Zhang, L.; Wang, H.; Shi, H.; Liu, Q. Simultaneous voltammetric detection of dopamine, ascorbic acid and uric acid using a poly(2-(N-morpholine)ethane sulfonic acid)/RGO modified electrode. RSC Adv, 2018, 8, 5280-5285.
Wang, Z.; Guo, H.; Gui, R.; Jin, H.; Xia, J.; Zhang, F. Simultaneous and selective measurement of dopamine and uric acid using glassy carbon electrodes modified with a complex of gold nanoparticles and multiwall carbon nanotubes. Sens. Actuat B Chem., 2018, 255, 2069-2077.
Fu, L.; Wang, A.; Lai, G.; Su, W.; Malherbe, F.; Yu, J.; Lin, C.T.; Yu, A. Defects regulating of graphene ink for electrochemical determination of ascorbic acid, dopamine and uric acid. Talanta, 2018, 180, 248-253.
Li, Q.; Huo, C.; Yi, K.; Zhou, L.; Su, L.; Hou, X. Preparation of flake hexagonal BN and its application in electrochemical detection of ascorbic acid, dopamine and uric acid. Sens. Actuat B Chem., 2018, 260, 346-356.
Tig, G.A. Development of electrochemical sensor for detection of ascorbic acid, dopamine, uric acid and L-tryptophan based on Ag nanoparticles and poly(L-arginine)-graphene oxide composite. J. Electroanal. Chem., 2017, 807, 19-28.
Yadav, D.K.; Gupta, R.; Ganesan, V.; Sonkar, P.K. Individual and simultaneous voltammetric determination of ascorbic acid, uric acid and folic acid by using a glassy carbon electrode modified with gold nanoparticles linked to bentonite via cysteine groups. Microchim. Acta, 2017, 184, 1951-1957.
Jesny, S.; Kumar, K.G. Electrocatalytic resolution of guanine, adenine and cytosine along with uric acid on poly (4-amino-3-hydroxy naphthalene-1-sulfonic acid) modified glassy carbon electrode. J. Electroanal. Chem., 2017, 801, 153-161.
Yao, Y.; Zhang, C. A novel screen-printed microfluidic paper-based electrochemical device for detection of glucose and uric acid in urine. Biomed. Microdevices, 2016, 18, 92.
Zou, C.; Zhong, J.; Li, S.; Wang, H.; Wang, J.; Yan, B.; Du, Y. Fabrication of reduced graphene oxide-bimetallic PdAu nanocomposites for the electrochemical determination of ascorbic acid, dopamine, uric acid and rutin. J. Electroanal. Chem., 2017, 805, 110-119.
Zhu, D.; Ma, H.; Pang, H.; Tan, L.; Jiao, J.; Chen, T. Facile fabrication of a non-enzymatic nanocomposite of heteropolyacids and CeO2@Pt alloy nanoparticles doped reduced graphene oxide and its application towards the simultaneous determination of xanthine and uric acid. Electrochim. Acta, 2018, 266, 54-65.
Tian, F.; Li, H.; Li, M.; Li, C.; Lei, Y.; Yang, B. A tantalum electrode coated with graphene nanowalls for simultaneous voltammetric determination of dopamine, uric acid, L-tyrosine, and hydrochlorothiazide. Microchim. Acta, 2017, 184, 1611-1619.
Liu, J.; Xie, Y.; Wang, K.; Zeng, Q.; Liu, R.; Liu, X. A nanocomposite consisting of carbon nanotubes and gold nanoparticles in an amphiphilic copolymer for voltammetric determination of dopamine, paracetamol and uric acid. Microchim. Acta, 2017, 184, 1739-1745.
Habib, I.H.I.; Rizk, M.S.; Abou El-Alaminb, M.M.; Imam, G.S. Cathodic stripping voltammetric determination of febuxostat in pharmaceutical dosage form and plasma samples. Port. Electrochemical. Acta, 2016, 34, 343-353.
Jain, R.; Sinha, A. Multi-walled carbon nanotubes-aluminium titanate nanocomposite sensor for electrocatalytic quantification of non-purine xanthine oxidase inhibitor febuxostat. Sci. Lett. J., 2015, 4, 151-155.
Jain, R.; Sinha, A. Dhanjai, Karolia, P.; Khan, A.L. Zinc oxide nanoflowers based graphene nanocomposite platform for catalytic studies of febuxostat. Int. J. Electrochem. Sci., 2016, 11, 10223-10237.
Nigović, B.; Milanović, I. Green electroanalytical method for fast measurement of xanthine oxidase inhibitor febuxostat. Anal. Sci., 2017, 33, 1219-1223.
Svítková, J.; Ignat, T. ˇSvorc, L’.; Labuda, J.; Barek, J. Chemical modification of boron-doped diamond electrodes for applications to biosensors and biosensing. Crit. Rev. Anal. Chem., 2016, 46, 248-256.
Pecková, K.; Musilová, J.; Barek, J. Boron-doped diamond film electrodes - new tool for voltammetric determination of organic substances. Crit. Rev. Anal. Chem., 2009, 39, 148-172.
Nigović, B.; Sadiković, M.; Jurić, S. Electrochemical sensing of mesalazine and its N-acetylated metabolite in biological samples using functionalized carbon nanotubes. Talanta, 2016, 147, 50-58.
Sadiković, M.; Nigović, B.; Jurić, S.; Mornar, A. Voltammetric determination of ropinirole in the presence of levodopa at the surface of a carbon nanotubes based electrochemical sensor in pharmaceuticals and human serum. J. Electroanal. Chem., 2014, 733, 60-68.
International Conference on Harmonization (ICH) Validation of Analytical Procedures: Text and Methodology Q2 (R1), 2005
Sano, K.; Kodama, Y.; Hirano, M.; Takishima, I.; Makino, A.; Nakamura, T.; Kitta, Y.; Kawabata, K.; Obata, J.; Kugiyama, K. High plasma levels of endogenous free dopamine predict an adverse outcome in patients with heart disease and chronic kidney disease. Circulation, 2008, 118, S434.

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Year: 2019
Published on: 30 July, 2018
Page: [678 - 684]
Pages: 7
DOI: 10.2174/1573411014666180730112905
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