1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 DOI: 10.1002/elan.201800021 Electrocatalytic Oxidation and Flow Injection Analysis of Isoniazid Drug Using an Unmodified Screen Printed Carbon Electrode in Neutral pH Manavalan Gopinathan, [a] Natarajan Thiyagarajan, [a] Murugan Thiruppathi, [a] and Jyh-Myng Zen* [a] Abstract: In this work we report electrocatalytic oxidation and flow injection analysis of tuberculostatic drug iso- niazid (INZ) based on a disposable and unmodified screen printed carbon electrode (SPCE). Instead of using chemi- cally modified electrode to increase the sensitivity at low overpotential, the same purpose can be achieved simply by preanodization of a bare SPCE in a suitable electrolyte medium. Surface characterization of the as-preanodized electrode by X-ray photoelectron spectroscopy and Ram- an spectroscopy indicate that both oxygen functionalities and edge/defect sites effectively assist the INZ oxidation. Flow injection analysis extends its applicability with a wide linear range up to 1 mM and an enhanced sensitivity of 100 nA mM 1 with a low detection limit of 2.7 nM (S/ N = 3). These good analytical features accomplished with disposable and economical devices could make possible the implementation of this methodology for INZ on-line monitoring in pharmaceuticals. Keywords: Isoniazid · Screen-printed carbon electrode · Preanodization · Disposable 1 Introduction Isoniazid (pyridine-4-carboxylic hydrazide, isonicotinic acid hydrazide, INZ) is an antibiotic and pulmonary tuberculosis agent. It has been widely used as such or in combination with rifampicin, pyrazinamide, and ethambu- tol HCl to overwhelm the resistance of mycobacterium tuberculosis [1–3]. As per WHO (World Health Organ- ization) guidelines, the allowable daily consumption of INZ should be between 4 and 6 mg kg 1 of human body weight and the allowable daily dose should not exceed 300 mg [4]. However, prolonged use or overdose of INZ tablet may cause hepatotoxicity and occasionally death. It is because during INZ metabolism hydrazine is produced and it induces hepatotoxicity [5]. Therefore, regular monitoring of INZ dosage level in human body fluids is crucial and the development of sensitive, effective, and consistent methods to quantify INZ in clinical and pharmaceutical samples is necessary [6]. Various analytical methods include titrimetry [7], fluorimetry [8], chemiluminescence [9], UV-visible spec- trophotometry [10], gas chromatography [11], high per- formance liquid chromatography [12], capillary electro- phoresis [13], and electrochemical techniques [14, 15] have been reported to detect and quantify INZ in human body fluids and pharmaceutical products. Since electrochemical method offers a rapid, cheap, sensitive and reproducible detection, much interest has garnered and steered the development of numerous chemically modified electrodes for detection of INZ and related compounds. For example, ordered mesoporous carbon modified glassy carbon elec- trode (GCE), multi-walled carbon nanotube paste modi- fied electrode were employed to detect INZ [16, 17]. Electrochemical sensor for the simultaneous voltammetric determination of ascorbic acid, acetaminophen and INZ using thionine immobilized multi-walled carbon nanotube modified carbon paste electrode was also demonstrated [18]. Nevertheless, the electrode often requires extensive modification to improve the sensitivity and detection limit at neutral medium. Along this line of interest, rhodium, gold-platinum core shell nanoparticles, and silver nano- particles incorporated in copolymer of methyl methacry- late and 2-acrylamido-2-methylpropane sulfonic acid modified GCE [19–21] have also been used for sensitive determination of INZ. Despite the significant improve- ment, the use of GCE obviously is not suitable for use as routine disposable electrodes. Screen printed carbon electrode (SPCE) offers signifi- cant advantages such as disposability, easy for mass production and flexible design [22, 23]. It is possible to generate a variety of functional groups over the electrode surface by carefully tuning the activation condition for various application. For example, the selective detection of creatinine based on Jaffe reaction, adsorption and oxidation of polyaromatic hydrocarbons and enhanced electrochemiluminescence besides other applications as- sisted by functional groups were demonstrated earlier [22, 30]. On the other hand, activated carbon electrodes have received considerable attention due to their defect sites, porous structure and oxygen functional groups with good adsorbing characteristics and improved electrochem- ical behaviour [24–29]. Previous studies have revealed the [a] M. Gopinathan, N. Thiyagarajan, M. Thiruppathi, J.-M. Zen Department of Chemistry, National Chung Hsing University, Taichung 402, Taiwan E-mail: jmzen@dragon.nchu.edu.tw Full Paper www.electroanalysis.wiley-vch.de # 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim Electroanalysis 2018, 30, 1 – 8 1 These are not the final page numbers! ÞÞ