Square-wave voltammetric determination of hydroxychloroquine in pharmaceutical and synthetic urine samples using a cathodically pretreated boron-doped diamond electrode Patrícia Batista Deroco a , Fernando Campanhã Vicentini a , Geiser Gabriel Oliveira b , Romeu C. Rocha-Filho a , Orlando Fatibello-Filho a,⇑ a Departamento de Química, Universidade Federal de São Carlos, Caixa Postal 676, 13560-970 São Carlos, SP, Brazil b Instituto de Química de São Carlos, Universidade de São Paulo, Caixa Postal 780, 13560-970 São Carlos, SP, Brazil article info Article history: Received 17 December 2013 Received in revised form 22 January 2014 Accepted 30 January 2014 Available online 8 February 2014 Keywords: Hydroxychloroquine electroanalytical determination BDD electrode Cathodic pretreatment Square-wave voltammetry abstract A square-wave voltammetry method for the determination of hydroxychloroquine (HCQ) in pharmaceu- tical and synthetic urine samples with a cathodically pretreated (CPT) boron-doped diamond (BDD) elec- trode was successfully developed. Using cyclic voltammetry, the HCQ oxidation was shown to be a one- electron diffusion-controlled process. The obtained SWV analytical curve (I pa /lA = 0.033 + 1.24 [HCQ/ (lmol L 1 )]) for HCQ determination (using 0.1 mol L 1 H 2 SO 4 as supporting electrolyte) presented a lin- ear response from 0.1 to 1.9 lmol L 1 , with a detection limit of 0.06 lmol L 1 , the best value attained yet with an unmodified electrode. The proposed method was successfully applied in the determination of HCQ in pharmaceutical (tablets) samples, with results similar at a 95% confidence level to those obtained using a reference spectrophotometric method. Additionally, adequate recovery results were obtained for the determination of HCQ in doped synthetic urine samples. The novel proposed method is inexpensive and fast, with no need of sample pretreatment. Ó 2014 Elsevier B.V. All rights reserved. 1. Introduction Hydroxychloroquine (HCQ), Fig. 1, is a drug derived from 4-ami- noquinoline. HCQ is used as an antimalarial drug ever since World War II. It is also widely used in the treatment of lupus erythemato- sus, rheumatoid arthritis, and other inflammatory and skin dis- eases [1–5]. When ingested, HCQ is rapidly absorbed by the intestine, accumulating in organs such as the liver, spleen, lungs, and kidneys, being partially converted to active metabolites in the liver and excreted primarily via the kidney (15–25% of it un- changed) [6]. In the eyes, this drug is deposited in all tissues that contain melanin; this can cause changes in the iris, choroid, and especially in the retinal pigment epithelium, generating retinopa- thy [3–5]. The toxicity of HCQ is a cause of ophthalmic concern, be- cause significant improvements in visual recovery are not observed even after the use of the drug is discontinued. According to studies reported in the literature [3,7–9], some risk factors increase the likelihood of retinopathy caused by HCQ; for example, the daily dosage (it should not exceed 6.5 mg kg 1 body weight), the cumu- lative dose, and renal or liver disease, besides age and previous ret- inal diseases. Thus, pharmaceuticals containing HCQ must undergo strict quality control, which requires the development of simple, rapid, and accurate analytical procedures for the identification and quantification of this drug in both pharmaceutical and biological samples. For the quantification of HCQ in pharmaceuti- cal tablets, the British Pharmacopoeia recommends the use of potentiometric titration in non-aqueous media [10]. Most of the described analytical procedures for the determination of HCQ in pharmaceutical formulations employ chromatographic techniques [11–15], which may have disadvantages such as the need of sam- ple pretreatment, long analysis time, and large consumption of chemicals, thereby generating high amounts of waste. Electroanalytical methods commonly have some advantages over chromatographic methods, such as lower consumption of chemicals, shorter analysis times, and lower cost of instrumenta- tion. Nevertheless, so far only two such methods for the determina- tion of HCQ have been reported in the literature, using glassy carbon (GC) electrodes, unmodified and modified [16,17]. Arguelho et al. [16] investigated the electrochemical reduction of HCQ at a GC electrode by cyclic voltammetry and chronoamperometry. Then, they developed an analytical method based on differential pulse voltammetry (DPV) and used it to assay HCQ in a pharmaceutical http://dx.doi.org/10.1016/j.jelechem.2014.01.037 1572-6657/Ó 2014 Elsevier B.V. All rights reserved. ⇑ Corresponding author. Tel.: +55 16 33518098; fax: +55 16 33518350. E-mail address: bello@ufscar.br (O. Fatibello-Filho). Journal of Electroanalytical Chemistry 719 (2014) 19–23 Contents lists available at ScienceDirect Journal of Electroanalytical Chemistry journal homepage: www.elsevier.com/locate/jelechem