http://www.revistadechimie.ro REV.CHIM.(Bucharest)♦69♦No. 10 ♦2018 2858 Simple Real-time Voltammetric Method for Captopril Determination in Pharmaceutical Formulation MIHAELA BULEANDRA 1 , ANTON ALEXANDRU CIUCU 1 *, DRAGOS CRISTIAN STEFANESCU 2,3 1 University of Bucharest, Faculty of Chemistry, Department of Analytical Chemistry, 90-92 Panduri Av., 050663, Bucharest, Romania 2 Carol Davila University, Medicine and Pharmacy Faculty, 8 Eroii SanitariStr., 050474, Bucharest, Romania 3 Gen. Dr. Aviator Victor Anastasiu National Institute of Aeronautical and Spatial Medicine, 88th Mircea Vulcanescu Str., 010825, Bucharest, Romania A novel voltammetric assay for captopril (CAP) determination by using an electrochemically pretreated pencil graphite electrode (PGE*) is presented. The electrochemical oxidation reaction of CAP was investigated with PGE* by using cyclic voltammetry and linear sweep voltammetry techniques. CAP was electrochemically inactive at the non-pretreated pencil graphite electrode surface, while a sharp anodic wave with an anodic peak potential at around 200 mV resulted by using the PGE*. According to kinetic studies upon the electrode behavior, a new reaction mechanism for electrochemical oxidation of captopril is proposed. The sensor was examined as a selective, simple and precise new electrochemical disposable electrode for the determination of CAP in pharmaceutical samples in complex medical cases associated with sleep apnea, with good results. Keywords: disposable sensor, dopamine, voltammetry, pharmaceutical samples, sleep apnea Captopril (CAP), 1-(3-mercapto-2-D-methyl-1- oxopropyl) proline, is used as a drug being an orally active inhibitor of the angiotensin-converting enzyme (ACE); by this action it causes artery walls to relax, lowering the blood pressure, improving so the pumping efficiency and cardiac output in patients with heart failure. Accordingly, CAP has been widely used for the treatment of hypertension, congestive heart failure, and left ventricular dysfunction after myocardial infarction [1]. This ACE inhibitor present a thiol group and can take up free radicals in living systems and exhibits antioxidant properties [2-4]. CAP is also sometimes prescribed for decreasing symptoms of cystinuria, reducing rheumatoid arthritis symptoms and treating Raynaud’s phenomena [5]. Administering CAP for therapeutic purposes leads to undesirable side effects like a dry, persistent cough [6]. Toxicity from CAP includes bone marrow suppression and proteinuria [7]. In some instances, liver dysfunction and skin yellowing have been reported with captopril administration [5,8]. Like other thiols, CAP undergoes rapid oxidation to disulphide metabolites both in vitro and in vivo where it is eliminated together with unchanged captopril (40–60%) in urine [9]. In solution, CAP undergoes an oxygen facilitated, first order and free radical oxidation at its thiol to yield captopril disulfide. The reaction rate depends on p H (oxidation is delayed using lower pH) and oxygen concentration. Its oxidative dimerization to a disulphide is a significant pharmaceutical problem. The determination of CAP is important in pharmacology and medicine for drug quality control purposes and to monitor patients with cardiovascular diseases (hypertension) or sleep disorders. The association between sleep apnea syndrome and high blood pressure is well documented, especially with respect to night-time hypertension. Normally, at night, the blood pressure drops, a phenomenon defined as dipping. Sleep apnea syndrome (SAS) appears to be responsible for a large number of cases of high blood pressure or no decrease during night time. Several analytical methods have already been applied for the determination of CAP in pharmaceutical formulations and clinical samples, including gas chromato- graphy [10], high-performance liquid chromatography [3,4,11], colorimetry [2], spectrophotometry [12], chemiluminescence [13], and capillary electrophoresis [14]. Electrochemical techniques represent an alternative to the spectrophotometric and chromatographic methods due to their well-known advantages like simplicity, speed and low cost [15]. Captopril with its thiol group can oxidize at the surface of various electrodes or chemically modified ones and was determinate by different electrochemical methods [5,7,8,11] of which we mention those coupled with linear sweep voltammetric technique [16-19]. Most of the mentioned methods are applied to the determination of captopril in tablet. Among many other sensors, pencil graphite electrode (PGE) was successfully used in multiple electroanalytical applications due to its unique and extremely useful properties [20]. A survey of the literature reveals that there is no report regarding the linear sweep voltammetric (LSV) determination of CAP using electrochemically pre-treated (activated) pencil graphite electrode (PGE*). Electrodes reported in the literature and coupled with this technique were chemically modified ones. They present some well- known disadvantages of which we mention the possible electrode surface passivation which blocks the electron transfer, and so a cleaning step or renewal of the electrode surface is required before each measurement [20]. By using disposable sensors this necessary step is avoided [21]. A facile LSV method based on a PGE* for CAP determination with a detection limit of 2.34 × 10 -5 M is reported. The proposed method applied for CAP determination in real pharmaceutical samples is fast, selective, sensitive, and environmentally friendly. *email: anton_ciucu@yahoo.com All authors contributed equally to this work.