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A Nanosensor System Based On Disuccinimydyl–CYP2E1 for Amperometric Detection of the Anti-Tuberculosis Drug, Pyrazinamide

Authors: R. F. Ajayi, U. Sidwaba, U. Feleni, S. F. Douman, E. Nxusani, L. Wilson, C. Rassie, O. Tovide, P. G. L. Baker, S. L. Vilakazi, R. Tshikhudo, E. I. Iwuoha

Abstract:

Pyrazinamide (PZA) is among the first-line pro-drugs  in the tuberculosis (TB) combination chemotherapy used to treat  Mycobacterium tuberculosis. Numerous reports have suggested that  hepatotoxicity due to pyrazinamide in patients is due to inappropriate  dosing. It is, therefore necessary to develop sensitive and reliable  techniques for determining the PZA metabolic profile of diagnosed  patients promptly and at point-of-care. This study reports the  determination of PZA based on nanobiosensor systems developed  from disuccinimidyl octanedioate modified Cytochrome P450-2E1  (CYP2E1) electrodeposited on gold substrates derivatised with  (poly(8-anilino-1-napthalene sulphonic acid) PANSA/PVP-AgNPs  nanocomposites. The rapid and sensitive amperometric PZA  detection gave a dynamic linear range of 2µM to 16µM revealing a  limit of detection of 0.044µM and a sensitivity of 1.38µA/µM. The  Michaelis-Menten parameters; KM, KM app and IMAX were calculated to  be 6.0µM, 1.41µM and 1.51x10-6 A, respectively, indicating a  nanobiosensor suitable for use in serum.

Keywords: Tuberculosis, cytochrome P450-2E1, pyrazinamide, Disuccinimidyl octanedioate

Digital Object Identifier (DOI): doi.org/10.5281/zenodo.1090478

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