Simple and Fast Determination of Warfarin in Pharmaceutical Samples Using Boron‐doped Diamond Electrode in BIA and FIA Systems with Multiple Pulse Amperometric Detection

This paper proposes the use of the boron‐doped diamond electrode (BDDE) in flow and batch injection analysis (FIA and BIA) systems with multiple‐pulse amperometric (MPA) detection for the determination of warfarin (WA) in pharmaceutical formulations. The electrochemical behavior of WA obtained by cyclic voltammetry (CV) in 0.1 mol L⁻¹ phosphate buffer shows an irreversible oxidation process at +1.0 V (vs Ag/AgCl). The MPA was based on the application of two sequential potential pulses as a function of time on BDDE: (1) for WA detection at +1.2 V/100 ms and; (2) for electrode surface cleaning at −0.2 V/200 ms. Both hydrodynamic systems (FIA‐MPA and BIA‐MPA) used for WA determination achieved high precision (with relative standard deviations around 2 %, n =10), wide linear range (2.0−400.0 μmol L⁻¹), low limits of detection (0.5 μmol L⁻¹) and good analytical frequency (94 h⁻¹ for FIA and 130 h⁻¹ for BIA). The WA determination made by the proposed methods was compared to the official spectrophotometric method. The FIA‐MPA and BIA‐MPA methods are simple and fast, being an attractive option for WA routine analysis in pharmaceutical industries.     

A Simple Strategy for Simultaneous Determination of Paracetamol and Caffeine Using Flow Injection Analysis with Multiple Pulse Amperometric Detection

In this work, we report a simple and novel strategy for simultaneous analysis using flow injection analysis with multiple pulse amperometric (FIA‐MPA) detection. The proposed strategy was successfully used for simultaneous determination of paracetamol and caffeine (model analytes) in pharmaceutical formulations. A sequence of potential pulses (waveform) was selected in such a way that PA is selectively oxidized at E₁ (+1.20 V/50 ms) and both compounds (PA+CA) are simultaneously oxidized at E₂ (+1.55 V/50 ms); hence, current subtraction (using a correction factor) can be used for the selective determination of CA. The proposed FIA method is simple, cheap, fast (140 injections h^?1), and present selectivity for the determination of both compounds in pharmaceutical samples, with results similar to those obtained by HPLC at a 95 % confidence level.     

Batch Injection Analysis‐Multiple Pulse Amperometric Fingerprint: A Simple Approach for Fast On‐site Screening of Drugs

In this work, the association of batch injection analysis with multiple pulse amperometric detection (BIA‐MPA) is presented as a new approach to obtain drugs fingerprints. To illustrate the potential of this screening method, tablets containing sildenafil as the active substance were used. Here, a sequence of three potential pulses as a function of time (+1.3, +1.6 and +2.1 V) were applied on a boron‐doped diamond electrode while reproducible injections were performed in a BIA cell (wall jet configuration). The chemical profile of the respective drug combined three ratios among the peak currents obtained in each amperogram: R₁=ipa_1.6V/ipa_1.3V, R₂=ipa_2.1V/ipa_1.6V, R₃=ipa_2.1V/ipa_1.3V. This simple protocol allowed discrimination between Viagra® (reference)/generic and two smuggled tablets, as well as pure Viagra® from Viagra® adulterated with other electroactive compounds (caffeine, dipyrone, paracetamol and tadalafil). For comparison, screening of these samples was also performed using square wave voltammetry combined with a chemometric method (principal component analysis), in which was achieved similar discrimination by one or other strategy for the most of drugs. This new BIA‐MPA fingerprinting combines desirable features in forensic science such as low cost, simplicity, high sample throughput (two drugs discerned in less than 30 s) and portability (screening at the place of the seizure).     

Fast and Simple Electrochemical Analysis Kit for Quality Control of Narrow Therapeutic Index Drugs

The use of multiple‐pulse amperometry (MPA) for the determination of narrow therapeutic index (NTI) drugs using batch injection analysis (BIA) with carbon screen‐printed electrodes (SPE) is proposed, seeking to develop a practical and low‐cost analysis kit for application in routine quality control of these drugs. The electrochemical behaviors of aminophylline, carbamazepine, clindamycin, colchicine, minoxidil, prazosin, procainamide, theophylline, warfarin and verapamil were evaluated in different electrolytes, but just one, the 0.1 mol L⁻¹ phosphate buffer, pH 7.0, was chosen for determination of all the analytes. The amperometric detection was optimized as a function of the best oxidation potential for carbon SPE for each analyte, which was in a range from 0.7 to 1.1 V. The injection conditions were determined as a function of the velocity and the volume injected by the BIA system, which were 92.5 μL s⁻¹ and 100 μL, respectively. Under these conditions, a good repeatability (RSD<3 %), high analytical frequency (>215 determinations per hour), large linear ranges and low LOD (<0.42 μmol L⁻¹) for all the NTI drugs were obtained. Furthermore, the proposed method provided an easy qualitative analysis of the investigated analytes using MPA detection. The addition‐recovery studies in pharmaceutical samples containing NTI drugs and the comparison with official methods showed that the proposed analysis Kit is a very fast, simple and efficient alternative for quantification of these analytes.     

Electrochemical Oxidation of Ibuprofen and Its Voltammetric Determination at a Boron‐Doped Diamond Electrode

The electrochemical oxidation of ibuprofen at a boron‐doped diamond electrode (BDDE) and its voltammetric determination is reported for the first time. A well‐defined oxidation peak was observed at around 1.6 V in 0.1 mol L^?1 H₂SO₄ solution with 10 % (v/v) ethanol at the BDDE surface activated by either cathodic or anodic pretreatments. A differential‐pulse voltammetric method for the determination of ibuprofen in pharmaceutical formulations was optimized with a detection limit of 5 µmol L^?1 and compared with the British Pharmacopeia method.     

Simultaneous Determination of Caffeine,Ibuprofen, and Paracetamol by Flow‐injection Analysis with Multiple‐pulse Amperometric Detection on Boron‐doped Diamond Electrode

This work presents a simple, fast and low‐cost method for the simultaneous determination of three drugs by flow‐injection analysis with multiple‐pulse amperometric (MPA) detection using a wall‐jet flow cell with a boron‐doped diamond electrode. The amperometric determination of caffeine (CF), ibuprofen (IB) and paracetamol (PC) was performed by the application of a four‐potential waveform using the MPA technique. PC is oxidized at E₁ (1.20 V/70 ms) and thus selectively detected; PC and CF are oxidized at E₂ (1.49 V/40 ms); PC, CF and IB are oxidized at E₃ (1.70 V/70 ms); and E₄ (1.80 V/100 ms) is applied for electrode cleaning. The subtraction of currents obtained at the different potentials did not provide accurate determinations of CF and IB, thus it was required to investigate correction factors to determine CF and IB without the interference from PC and CF using the respective amperometric signals obtained at E₂ and E₃. The proposed method was successfully applied for the determination of three drugs in pharmaceutical samples with low generation of residues and a high analytical frequency (150 h^?1) in comparison with HPLC‐DAD method.     

Simultaneous determination of acetylsalicylic acid and salicylic acid in human plasma by isocratic high‐pressure liquid chromatography with post‐column hydrolysis and fluorescence detection

A selective, sensitive and rapid high‐performance liquid chromatography method with post‐column hydrolysis and fluorescence detection was developed for the simultaneous quantification of acetylsalicylic acid and its metabolite salicylic acid in human plasma. Following the addition of 2‐hydroxy‐3‐methoxybenzoic acid as internal standard and simple protein precipitation with acetonitrile, the analytes were separated on a ProntoSIL 120 C₁₈ ace‐EPS column (150 × 2 mm, 3 µm) protected by a C₈ guard column (5 µm). The mobile phase, 10 mm formic acid in water (pH 2.9) and acetonitrile (70:30, v/v), was used at a flow rate of 0.35 mL/min. After on‐line post‐column hydrolysis of acetylsalicylic acid (ASA) to salicylic acid (SA) by addition of alkaline solution, the analytes were measured at 290 nm (λ_ex) and 400 nm (λ_em). The method was linear in the concentration ranges between 0.05 and 20 ng/μL for both ASA and SA with a lower limit of quantification of 25 pg/μL for SA and 50 pg/μL for ASA. The limit of detection was 15 pg/μL for SA and 32.5 pg/μL for ASA. The analysis of ASA and SA can be carried out within 8 min; therefore this method is suitable for measuring plasma concentrations of salicylates in clinical routine. Copyright © 2012 John Wiley & Sons, Ltd.     

Voltammetric determination of mesalazine in pharmaceutical preparations and biological samples using boron-doped diamond electrode

Voltammetric method for the determination of non-steroidal anti-inflammatory drug mesalazine (5-ASA) is presented for the first time using boron-doped diamond electrode (BDDE). 5-ASA provides one well-developed SWV oxidation peak at about ?900 mV (vs. saturated silver/silver chloride reference electrode) on BDDE. Britton-Robinson buffer (pH 7.0) was chosen as an optimal supporting electrolyte for the determination of 5-ASA using square wave voltammetry (SWV). Parameters of SWV were developed and low limit of detection (7.0 × 10^?7 mol L^?1) was reached. In addition, relative standard deviation of repeated measurements (c _5-ASA = 5 × 10^?5 mol L^?1, RSD_M = 2.7%) and relative standard deviation of repeated determinations (RSD_D < 1.5%) were calculated and confirm obtained good results. Applicability of the proposed method was verified by an analysis of a pharmaceutical preparation and spiked human urine.     

Simultaneous Determination of Acetaminophen and Ascorbic Acid at an Unmodified Boron‐Doped Diamond Electrode by Differential Pulse Voltammetry in Buffered Media

A boron‐doped diamond electrode (BDDE) was used for the simultaneous anodic determination of L ‐ascorbic acid (AA) and acetaminophen (AC) in aqueous buffered media by differential pulse voltammetry (DPV). Linear calibration plots of anodic current peaks versus concentration were obtained for both analytes in the concentration range 0.01–0.1 mM with very high correlation coefficients. RSD of 2–3% and high sensitivities were obtained from DPV data in single and dicomponent systems. The potential applicability of the DPV technique associated with standard addition was illustrated by simultaneous determination of AA and AC in real sample solutions made up from pharmaceutical products.     

Development of a Novel Versatile Method for Determination of two Antihistamines in Association with Naphazoline Using Cathodically Pretreated Boron‐doped Diamond Electrode

Antihistamines such as pheniramine (PHN) or chlorpheniramine (CPH) are commonly associated with naphazoline (NPZ) in eye drops and nasal decongestants. In this work, a batch‐injection analysis system with multiple pulse amperometric (BIA‐MPA) detection has been applied for the first time for fast simultaneous determination of naphazoline (NPZ) and pheniramine (PHN) or NPZ and chlorpheniramine (CPH). PHN or CPH was selectively detected at +1.1 V and both PHN and NPZ or CPH and NPZ were detected at +1.3 V using boron doped diamond (BDD) as working electrode and Britton‐Robinson (BR) buffer (pH=10.0) as supporting electrolyte. The current of NPZ can then be obtained by subtraction of the currents detected at both potential pulses and applying a correction factor (CF). The proposed method presented good intra‐day repeatability (RSD between 0.7 and 3.2 % for PHN; 0.7 and 2.1 % for CPH; 1.5 and 4.0 % for NPZ; n=20), high analytical frequency (>80 injections h⁻¹), and limits of detection of 0.64, 0.47 and 0.11 μmol L⁻¹ for PHN, CPH and NPZ, respectively. The results obtained with the proposed method are in agreement with those obtained by HPLC (95 % confidence level).     

Development of a Simple and Fast Electrochemical Method for Screening and Stoichiometric Determination of Dimenhydrinate

Dimenhydrinate (DIM) is a salt composed by the combination of two active pharmaceutical ingredients: diphenhydramine (DIP) and 8‐chlorotheophylline (CTP). In this work, the use of batch injection analysis with multiple pulse amperometric detection (BIA‐MPA) was proposed for the first time for fast stoichiometric determination of DIM. DIP (cation) and CTP (anion) were determined simultaneously in pharmaceutical samples with a simple and fast injection procedure (70 injections h^?1). Additional strategies were also proposed for rapid screening of samples containing the DIM salt. By a simple injection of a sample into the BIA system (without using of calibration curve), reliable information about stoichiometry of the DIM salt (1 : 1; DIP:CTP) and presence or absence of interfering species (electroactive) can be achieved.     

Carbon‐nanotube Modified Screen‐printed Electrode for the Simultaneous Determination of Nitrite and Uric Acid in Biological Fluids Using Batch‐injection Amperometric Detection

A portable electroanalytical system applied for rapid and simultaneous determination of uric acid (UA) and nitrite (NIT) in human biological fluids (urine, saliva and blood) is reported. The system is based on batch‐injection analysis with multiple‐pulse amperometric (BIA‐MPA) detection using screen‐printed electrodes (SPEs) modified with multi‐walled carbon nanotubes. Sample dilution in optimized electrolyte (0.1 mol L⁻¹ Britton‐Robinson buffer pH 2) followed by injection of 100 μL on the electrode surface using an electronic micropipette is performed. UA is detected at +0.45 V and both UA+NIT at +0.70 V. Linear calibration plots for UA and NIT were obtained over the range of 1–500 μmol L⁻¹ with detection limits of 0.05 and 0.06 μmol L⁻¹, respectively. For comparison, a differential‐pulse voltammetric (DPV) method was optimized, and linear calibration plots for UA and NIT were obtained over range of 1–30 μmol L⁻¹ and 1–40 μmol L⁻¹ with detection limits of 0.1 and 0.3 μmol L⁻¹, respectively. BIA‐MPA is highly precise (RSD<1.3 %), fast (160 h⁻¹) and free from sample‐matrix interferences as recovery values ranged from 77 to 121 % for spiked samples (short contact time of sample aliquot with SPE). Contrarily, recovery tests conducted using DPV did not provide adequate recovery values (>150 %), probably due to the longer contact time of the SPE with the biological samples during analysis leading to a severe interference of sample matrices.     

Simultaneous Determination of 4‐Chlorophenol and Oxalic Acid Using an Expanded Graphite‐Epoxy Composite Electrode

An expanded graphite‐epoxy composite electrode (EG‐Epoxy) was employed for the simultaneous determination of 4‐chlorophenol (4‐CP) and oxalic acid (OA) by using cyclic voltammetry (CV), chronoamperometry (CA), and differential pulse voltammetry (DPV). The results indicated that OA could be determined in the presence of the same concentrations of 4‐CP within the concentration range of 0.1 mM to 0.5 mM with a relative standard deviation (RSD) smaller than 5%. Electrode fouling occurred during CA for 4‐CP concentrations larger than 0.5 mM. The DPV method was used for the simultaneous determination of 4‐CP and OA before and after electrochemical oxidation by chronopotentiometry under galvanostatic conditions (j=0.04 mA cm^?2, t=2 h) of a tap water sample spiked with 0.19 mM 4‐CP and 0.1 M Na₂SO₄.     

Selective Determination of Verapamil in Pharmaceutics and Urine Using a Boron‐doped Diamond Electrode Coupled to Flow Injection Analysis with Multiple‐pulse Amperometric Detection

This work presents a simple and low‐cost method for fast and selective determination of Verapamil (VP) in tablets and human urine samples using a boron‐doped diamond working electrode (BDD) coupled to a flow injection analysis system with multiple pulse amperometric detection (FIA‐MPA). The electrochemical behaviour of VP in 0.1 mol L⁻¹ sulfuric acid showed three merged oxidation peaks at around +1.4 V and upon reverse scan, one reduction peak at 0.0 V (vs. Ag/AgCl). The MPA detection was performed applying a sequence of three potential pulses on BDD electrode: (1) at +1.6 V for VP oxidation, (2) at +0.2 V for reduction of the oxidized product and (3) at +0.1 V for cleaning of the working electrode surface. The FIA system was optimized with injection volume of 150 μL and flow rate of 3.5 mL min⁻¹. The method showed a linear range from 0.8 to 40.0 μmol L⁻¹ (R>0.99) with a low limit of detection of 0.16 μmol L⁻¹, good repeatability (RSD<2.2 %; n=10) and sample throughput (45 h⁻¹). Selective determination of VP in urine was performed at+0.2 V due to absence of interference from ascorbic and uric acids in this potential. The addition‐recovery tests in both samples were close to 100 % and the results were similar to an official method.     

Determination of Abacavir, Lamivudine and Zidovudine in Pharmaceutical Tablets, Human Serum and in Drug Dissolution Studies by HPLC

A simple, accurate, precise and fully automated method for the simultaneous determination of abacavir, lamivudine and zidovudine in pharmaceutical tablets, human serum samples and drug dissolution studies has been developed. Separation was performed on a 5 μm Zorbax^® C₁₈ column (150 × 4.6 mm ID) with methanol:water:phosphate buffer at pH 5.65 (80:10:10; v/v/v) isocratic elution in less than 7 min with a flow rate of 0.6 mL min^?1.Good sensitivity for all analytes was observed with UV detection at 275 nm. The method allowed quantitation over the 500–3,000 ng mL^?1 range for abacavir and 500–5,000 ng mL^?1 range for lamivudine and zidovudine. The method has been applied, without any interference from excipients or endogenous substances, for the simultaneous determination of these three compounds in tablets. Human serum and drug dissolution studies.     

Simultaneous determination of atenolol,chlorthalidone and amiloride in pharmaceutical preparations by capillary zone electrophoresis with ultraviolet detection

Capillary zone electrophoresis methods for the simultaneous determination of the β‐blocker drugs, atenolol, chlorthalidone and amiloride, in pharmaceutical formulations have been developed. The influences of several factors (buffer pH, concentration, applied voltage, capillary temperature and injection time) were studied. Using phenobarbital as internal standard, the analytes were all separated in less than 4 min. The separation was carried out in normal polarity mode at 25°C, 25 kV and using hydrodynamic injection (10 s). The separation was effected in an uncoated fused‐silica capillary (75 μm i.d. × 52 cm) and a background electrolyte of 25 mm H₃PO₄ adjusted with 1 m NaOH solution (pH 9.0) and detection at 198 nm. The method was validated with respect to linearity, limit of detection and quantification, accuracy, precision and selectivity. Calibration curves were linear over the range 1–250 μg/mL for atenolol and chlorthalidone and from 2.5–250 μg/mL for amiloride. The relative standard deviations of intra‐ and inter‐day migration times and corrected peak areas were less than 6.0%. The method showed good precision and accuracy and was successfully applied to the simultaneous determination of atenolol, chlorthalidone and amiloride in various pharmaceutical tablets formulations. Copyright © 2010 John Wiley & Sons, Ltd.     

On‐Site Determination of Carbendazim,Cathecol and Hydroquinone in Tap Water Using a Homemade Batch Injection Analysis Cell for Screen Printed Electrodes

In this work, we present a simple homemade batch‐injection analysis cell for screen‐printed electrodes (BIA‐SPE). The potential of the proposed system for on‐site analysis was demonstrated by the determination of carbendazim, catechol, and hydroquinone in tap water. The system provided reduced injection volume (30 µL), high analytical frequency (≈200 h^?1) and low detection limits (nanomolar level). Moreover, the BIA‐SPE cell presented better stability (RSD≈0.4 %) than a conventional flow injection cell for SPE (RSD≈5.0 %) in organic media. The proposed homemade BIA‐SPE cell is very simple, inexpensive and can be easily constructed in any laboratory.     

Voltammetry as the First Method for Direct Determination of a Novel Antagonist of A2A Adenosine Receptors

In this article, for the first time, the analytical method for determination of a novel antagonist of A_2A adenosine receptors (8‐(4‐methoxyphenyl)‐4‐oxo‐4,6,7,8‐tetrahydroimidazo[2,1‐c][1,2,4]triazine‐3‐carbohydrazide, namely IMT), which can be used as a drug for liver diseases, was presented. For this purpose a commercially available boron‐doped diamond electrode (BDDE) in combination with differential pulse voltammetry (DPV) was applied. It was found by cyclic voltammetry (CV) that IMT displays at BDDE, as a sensor, two well‐defined oxidation peaks at potentials of 0.81 and 1.18 V and one reduction peak at 1.1 V vs. Ag/AgCl in 0.1 mol L^?1 acetate buffer (pH 4.5±0.1). The oxidation and reduction mechanism of IMT was proposed. The developed DPV method allowed the successful determination of IMT in the range of 0.05–50 μmol L^?1 with detection limit equal to 0.0094 μmol L^?1 and without any chemical modifications and electrochemical pretreatment of the electrode surface. The proposed procedure allows the determination of IMT in vitro directly from urine samples.     

Determination of Amlodipine and Atenolol by Batch Injection Analysis with Amperometric Detection on Boron‐doped Diamond Electrode

This work describes the sequential determination of amlodipine (AML) and atenolol (ATN) by batch injection analysis (BIA) with pulsed amperometric detection (BIA‐PAD). Boron doped diamond (BDD) was used as working electrode. AML was detected at +1.00 V and ATN at +1.65 V. The proposed BIA method is simple, robust, precise (RSD <3.2 %; n=10), presents high analytical frequency (>70 injections h^?1), generates reduced volume of waste (without use of organic solvent) and requires minimal sample manipulation (dissolution and dilution in electrolyte). The limits of detection were 0.074 and 0.073 µmol L^?1 for AML and ATN, respectively. The results obtained with the proposed BIA method were compared to those obtained by HPLC and similar results were obtained (at 95% of confidence level).     

Simultaneous Determination of Atenolol and Chlorthalidone in Pharmaceutical Preparations by Capillary-Zone Electrophoresis

Abstract

A capillary zone electrophoresis (CZE) method for the simultaneous determination of the β-blocker drugs atenolol and chlorthalidone in pharmaceutical formulations has been developed. The CZE separation was performed under the following conditions: capillary temperature, 25°C; applied voltage, 25 kV; 20 mM H₃PO₄–NaOH running buffer (pH 9.0); and detection wavelength, 198 nm. Phenobarbital was used as internal standard. The method was validated and showed not only good precision and accuracy but also good robustness. The method has been successfully applied to the simultaneous determination of both atenolol and chlorthalidone in pharmaceutical tablets.