Analysis of fexofenadine in pharmaceutical formulations using tris(1,10‐phenanthroline)–ruthenium(II) peroxydisulphate chemiluminescence system in a multichip device

A simple, rapid and sensitive method has been developed for the analysis of fexofenadine (FEX) in pharmaceutical formulations, using a tris(1,10‐phenanthroline)–ruthenium(II) [Ru(phen)₃²⁺] peroxydisulphate chemiluminescence (CL) system in a multichip device. Various parameters that influence the CL signal intensity were optimized. These included pH, flow rates and concentration of reagents used. Under optimum conditions, a linear calibration curve in the range 0.05–5.0 µg/mL was obtained. The detection limit was found to be 0.001 µg/mL. The procedure was applied to the analysis of FEX in pharmaceutical products and was found to be free from interference from concomitants usually present in these preparations. Copyright © 2011 John Wiley & Sons, Ltd.     

Photoinduced oxidation of a tris(2,2'‐bipyridyl)ruthenium(II)–peroxodisulfate chemiluminescence system for the analysis of mebeverine HCl pharmaceutical formulations and biological fluids using a two‐chip device

A new method for the analysis of mebeverine hydrochloride (MEB) has been developed using a two‐chip device. The method is highly selective, sensitive, rapid and consumes minute amount of reagents. The developed method is free of interference from the degradation products of MEB and from common ingredients present in pharmaceutical formulations. The limit of detection was 0.043 µg/mL, and the limit of quantification was 0.138 µg/mL. The short analysis time per sample (20 s) allowed a large number of analyses to be performed within a very short time. Various samples were analyzed, including two different pharmaceutical formulations and a uniformity of content analysis for 20 tablets from a known batch and two biological samples at different concentrations. In addition, the method was compared with a validated high‐performance liquid chromatography (HPLC) method and the results clearly indicated the suitability of the developed method for routine analyses. A new mechanism for the tris(2,2'‐bipyridyl)ruthenium(II) (Ru(bpy)₃²⁺)‐peroxodisulfate (S₂O₈^2?) chemiluminescence (CL) system has also been proposed. The mechanism is based on photoinduced oxidation of Ru(bpy)₃²⁺ to Ru(bpy)₃³⁺ via the formation of Ru(bpy)₃²⁺* upon irradiation with visible light. S₂O₈^2? then oxidizes Ru(bpy)₃²⁺* to Ru(bpy)₃³⁺ and the analyte subsequently reduces the resultant Ru(bpy)₃³⁺ to Ru(bpy)₃²⁺*, which then produces the CL signal. Copyright © 2013 John Wiley & Sons, Ltd.     

Determination of folates by HPLC‐chemiluminescence using a ruthenium(II)–cerium(IV) system,and its application to pharmaceutical preparations and supplements

A chemiluminescence (CL) reaction of folic acid (FA) with ruthenium (II) and cerium (IV) was applied to quantify FA‐related compounds such as FA, dihydrofolic acid, tetrahydrofolic acid, 5‐methyltetrahydrofolic acid, 5‐formyltetrahydrofolic acid and methotrexate (MTX). Among the FAs, 5‐methyltetrahydrofolic acid provided the highest CL intensity. HPLC‐CL detection of FA was applied to quantify FA in pharmaceutical preparations and supplements. Analytical samples were separated on a semi‐micro ODS column with a mixture of 20 mM phosphate buffer (pH 5.7) and acetonitrile (94 : 6, v/v %). The separated samples were mixed with a post‐column CL reagent consisting of 1.5 mM Ru(bipy)₃²⁺ and 1.0 mM Ce(SO₄)₂, then the generated CL was monitored. The calibration range for FA was 10–100 μM and the limit of detection was 1.34 μM (signal‐to‐noise ratio of 3). Repeatabilities were 4.2, 4.6 and 5.0 RSD% (10, 25, 50 μM), and the recoveries for FA supplement, vitamin B complex supplement and FA‐containing medication (tablet) were 102.4 ± 10.5, 103.3 ± 13.3 and 100.3 ± 8.5%, respectively. The described method is robust against changes in the chromatographic parameters of ± 3.3 or ± 1.5%. The measured FA content corresponded well to the labeled content of FA‐containing products (100.6–104.9%), demonstrating the precision and accuracy of this method for the evaluation of FA pharmaceutical preparations. Copyright © 2014 John Wiley & Sons, Ltd.     

Determination of oxalate in urine and plasma using reversed-phase ion-pair high-performance liquid chromatography with tris(2,2′-bipyridyl)ruthenium(II)-electrogenerated chemiluminescence detection

Oxalate is quantitated in both urine and plasma samples using reversed-phase ion-pair high-performance liquid chromatography (HPLC) with tris(2,2′-bipyridyl)ruthenium(II) [Ru(bpy)₃²⁺]-electrogenerated chemiluminescent (ECL) detection. Underivatized oxalate was separated on a reversed-phase column (Zorbax ODS) using a mobile phase of 10% methanol in 100 mM phsophate buffer at pH 7.0. The eluted compounds were combined with a stream of 2 mM Ru(bpy)₃²⁺ at a mixing tee before the ECL flow-cell. In the flow-cell, Ru(bpy)₃²⁺ is oxidized to Ru(bpy)₃²⁺ at a platinum electrode, and reacts with oxalate to produce chemiluminescence (CL). Urine samples were filtered and diluted prior to injection. Plasma samples were deproteinized before injection. A 25-μl aliquot of sample was injected for analysis. Possible interferants, including amino acids and indole-based compounds, present in biological samples were investigated. Without the separation, amino acids interfere by increasing the total observed CL intensity; this is expected because they give rise to CL emission on their own in reaction with Ru(bpy)₃³⁺. Indole compounds exhibit a unique interference by decreasing the CL signal when present with oxalate. Indoles inhibit their own CL emission at high concentration. By use of the indicated HPLC separation, oxalate was adequately separated from both types of interferants, which thus had no effect on the oxalate signal. Urine samples were assayed by both HPLC and enzymatic tests, the two techniques giving similar results, differing only by 1%. Detection limits were determined to be below 1 μM (1 nmol/ml) or 25 pmol injected. The working curve for oxalate was linear throughout the entire clinical range in both urine and plasma.     

Chemiluminescence selectivity enhancement in the on‐chip Ru(bpy)32+ system: The potential role of buffer type and pH in the determination of hydrochlorothiazide in combined formulations and human plasma

A simple and highly selective on‐chip Ru(bpy)₃²⁺–oxidant chemiluminescence (CL) approach for estimation of a diuretic drug, hydrochlorothiazide (HCZ), in biological fluids was realized in the presence of other fixed‐dose combination drugs by manipulating simultaneously the method of active species (Ru(bpy)₃³⁺) production and type of carrier buffer with pH used for the CL reaction. Chemical oxidation processes involved in the Ru(bpy)₃²⁺–Ce(IV) CL system have been successfully miniaturised in this study using a microfabricated device to generate Ru(bpy)₃³⁺ instantaneously. The proposed system was then screened using HCZ and other drugs in the presence of various buffers and pH to explore the difference in CL emission. Ammonium formate buffer (0.15 M) at pH 4.5 exhibited excellent selectivity towards HCZ when Ru(bpy)₃³⁺ was produced by chemical oxidation using Ce(IV). The newly developed conditions do not involve any kind of prior separation or isolation procedure to remove other combination therapy drugs in formulation and biological samples. The method under fully optimised conditions exhibited wide linearity over the concentration range 0.5–1000 ng ml^?1 and low detection and quantification limits of 0.13 and 0.47 ng ml^?1 respectively for HCZ. Acceptable levels of recoveries were obtained for HCZ from human plasma using the proposed method (98.9–100.8%) in the presence of other antihypertensive combination therapy drugs. This study postulates that such miniaturised devices may find applications especially for on‐site analysis, such as doping control examinations.     

Chemiluminescence determination of chlorpheniramine using tris(1,10‐phenanthroline)–ruthenium(II) peroxydisulphate system and sequential injection analysis

A sequential injection (SI) method was developed for the determination of chlorpheniramine (CPA), based on the reaction of this drug with tris(1,10‐phenanthroline)–ruthenium(II) [Ru(phen)₃²⁺] and peroxydisulphate (S₂O₈^2–) in the presence of light. The instrumental set‐up utilized a syringe pump and a multiposition valve to aspirate the reagents [Ru(phen)₃²⁺ and S₂O₈^2–] and a peristaltic pump to propel the sample. The experimental conditions affecting the chemiluminescence reaction were systematically optimized, using the univariate approach. Under the optimum conditions linear calibration curves of 0.1–10 µg/ml were obtained. The detection limit was 0.04 µg/ml and the relative standard deviation (RSD) was always < 5%. The procedure was applied to the analysis of CPA in pharmaceutical products and was found to be free from interferences from concomitants usually present in these preparations. Copyright © 2008 John Wiley & Sons, Ltd.     

Large enhancement of oscillating chemiluminescence with [Ru(bpy)3]2+‐catalyzed Belousov–Zhabotinsky reaction in the presence of tri‐n‐propylamine

Oscillating chemiluminescence enhanced by the addition of tri‐n‐propylamine (TPrA) to the typical Belousov–Zhabotinsky (BZ) reaction system catalyzed by ruthenium(II)tris(2.2'‐bipyridine)(Ru(bpy)₃²⁺) was investigated using a luminometry method. The [Ru(bpy)₃]²⁺/TPrA system was first used as the catalyst for a BZ oscillator in a closed system, which exhibited a shorter induction period, higher amplitude and much more stable chemiluminescence (CL) oscillation. The effects of various concentrations of TPrA, oxygen and nitrogen flow rate on the oscillating behavior of this system were examined. In addition, the CL intensity of the [Ru(bpy)₃]²⁺/TPrA–BZ system was found to be inhibited by phenol, thus providing a way for use of the BZ system in the determination of phenolic compounds. Moreover, the possible mechanism of the oscillating CL reaction catalyzed by [Ru(bpy)₃]²⁺/TPrA and the inhibition effects of oxygen and phenol on this oscillating CL system were considered. Copyright © 2012 John Wiley & Sons, Ltd.     

Determination of oxytetracycline hydrochloride in milk and egg white samples using Ru(bipy)32+–Ce(SO4)2 chemiluminescence

A novel, rapid and sensitive chemiluminescence (CL) method for the determination of oxytetracycline hydrochloride (OTCH) is described in this paper. The presented method was based on the fact that OTCH could immensely enhance the CL of the reaction of cerium sulfate and tris(2,2‐bipyridyl) ruthenium (II) in acidic medium. Under optimal experimental conditions, CL intensity was favorably linear for OTCH in the range 5.0 × 10^?7 to 5.0 × 10^?5 g/ml, with a detection limit of 1.5 × 10^?7 g/ml (S/N = 3). The relative standard detection was 4.76% for 5.0 × 10^?6 g/ml (n = 11). This method was successfully applied to the analysis of OTCH in milk and egg white samples. According to the results of the kinetic curves for OTCH in the Ru(bipy)₃²⁺–Ce(SO₄)₂ CL system, together with CL and ultraviolet (UV)–visible spectra, the possible mechanism of the CL reaction is discussed briefly.     

Determination of sulpiride in pharmaceutical preparations and biological fluids using a Cr (III) enhanced chemiluminescence method

A highly sensitive and simple method for identifying sulpiride in pharmaceutical formulations and biological fluids is presented. The method is based on increased chemiluminescence (CL) intensity of a luminol–H₂O₂ system in response to the addition of Cr (III) under alkaline conditions. The CL intensity of the luminol–H₂O₂–Cr (III) system was greatly enhanced by the addition of sulpiride and the CL intensity was proportional to the concentration of sulpiride in a sample solution. Various parameters affecting the CL intensity were systematically investigated and optimized for determination of the sulpiride in a sample. Under the optimum conditions, the CL intensity was proportional to the concentration of sulpiride in the range of 0.068–4.0 µg/mL, with a good correlation coefficient of 0.997. The limit of detection (LOD) and limit of quantification (LOQ) were found to be 8.50 × 10^‐6 µg/mL and 2.83 × 10^‐5 µg/mL, respectively. The method presented here produced good reproducibility with a relative standard deviation (RSD) of 2.70% (n = 7). The effects of common excipients and metal ions were studied for their interference effect. The method was validated statistically through recovery studies and successfully applied for the determination of sulpiride in pure form, pharmaceutical preparations and spiked human plasma samples. The percentage recoveries were found to range from 99.10 to 100.05% for pure form, 98.12 to 100.18% for pharmaceutical preparations and 97.9 to 101.4% for spiked human plasma. Copyright © 2012 John Wiley & Sons, Ltd.     

Determination of estradiol valerate in pharmaceutical preparations and human serum by flow injection chemiluminescence

A novel method for the detection of trace estradiol valerate (EV) in pharmaceutical preparations and human serum was developed by inhibition of luminol chemiluminescence (CL) by estradiol valerate on the zinc deuteroporphyrin (ZnDP)‐enhanced luminol‐K₃Fe(CN)₆ chemiluminescence system. Under optimized experimental conditions, CL intensity and concentration of estradiol valerate had a good linear relationship in the ranges of 8.0 × 10^‐8 to 1.0 × 10^‐5 g/mL. Detection limit (3σ) was estimated to be 3.5 × 10^‐8 g/mL. The proposed method was applied successfully for the determination of estradiol valerate in pharmaceutical preparations and human serum and recoveries were 97.0‐105.0% and 95.5‐106.0%, respectively. The possible mechanism of the CL system is discussed. Copyright © 2012 John Wiley & Sons, Ltd.     

Investigation on 1O2 generation ability of di‐sulfonic phthalocyanine zinc isomers using an HPLC–CL system

An HPLC system combining a chemiluminescence detector was applied to estimate the singlet oxygen (¹O₂) generation ability of di‐sulfonic phthalocyanine zinc (ZnPcS₂) isomers. As photosensitizers, ZnPcS₂ produces ¹O₂ in air‐saturated solutions under photoirradiation. The latter reacts with methyl Cypridina luciferin analogue (MCLA) to initiate chemiluminescence. This photoinduced chemiluminescence (PCL) of MCLA provides an easy method for evaluating the isomers' ¹O₂ generation ability during a simultaneous HPLC separation procedure. The cis‐isomers and trans‐isomers of ZnPcS₂ show different ¹O₂ generation abilities, which are in accordance with differences in their absorption spectra. Copyright © 2013 John Wiley & Sons, Ltd.     

Simple chemiluminescence determination of ketotifen using tris(1,10 phenanthroline)ruthenium(II)‐ Ce(IV) system

A new method using chemiluminescence (CL) detection has been developed for the simple determination of ketotifen fumarate (KF). The method is based on the catalytic effect of KF in the CL reaction of tris(1,10 phenanthroline)ruthenium(II), Ru(phen)₃²⁺, with Ce(IV) in sulfuric acid medium. The CL response was detected using a lab‐made chemiluminometer. Effects of chemical variables were investigated and under optimum conditions, the CL intensity was proportional to the concentration of the drug over the range 0.34‐34.00 µg mL^?1 KF. The limit of detection (S/N=3) was 0.09 µg mL^?1. Effects of common ingredients were investigated and the method was applied successfully for determining KF in pharmaceutical formulations and human plasma. The percent of relative standard deviation (n=11) at level of 3.4 µg mL^?1 of KF was 4.6% and the minimum sampling rate was 70 samples per hour. The possible CL mechanism is proposed based on the kinetic characteristic of the CL reaction, CL spectrum, UV‐Vis and phosphorescence spectra. Copyright © 2015 John Wiley & Sons, Ltd.     

Determination of pioglitazone hydrochloride by flow injection chemiluminescence tris(2,2′-bipyridyl)ruthenium(II)–silver(III) complex system

A novel flow injection-chemiluminescence (FI–CL) approach is proposed for the assay of pioglitazone hydrochloride (PG-HCl) based on its enhancing influence on the tris(2,2′-bipyridyl)ruthenium(II)–silver(III) complex (Ru(bipy)₃²⁺-DPA) CL system in sulfuric acid medium. The possible CL reaction mechanism is discussed with CL and ultraviolet (UV) spectra. The optimum experimental conditions were found as: Ru(bipy)₃²⁺, 5.0 × 10⁻⁵ M; sulfuric acid, 1.0 × 10⁻³ M; diperiodatoargentate(III) (DPA), 1.0 × 10⁻⁴ M; potassium hydroxide, 1.0 × 10⁻³ M; flow rate 4.0 ml min⁻¹ for each flow stream and sample loop volume, 180 μl. The CL intensity of PG-HCl was linear in the range of 1.0 × 10⁻³ to 5.0 mg L⁻¹ (R² = 0.9998, n = 10) with limit of detection [LOD, signal-to-noise ratio (S/N) = 3] of 2.2 × 10⁻⁴ mg L⁻¹, limit of quantification (LOQ, S/N = 10) of 6.7 × 10⁻⁴ mg L⁻¹, relative standard deviation (RSD) of 1.0 to 3.3% and sampling rate of 106 h⁻¹. The methodology was satisfactorily used to quantify PG-HCl in pharmaceutical tablets with recoveries ranging from 93.17 to 102.77 and RSD from 1.9 to 2.8%.     

Nepem‐211 ion exchange conductive membrane immobilized tris(2,2´‐bipyridyl) ruthenium(II) electrogenerated chemiluminescence flow sensor for high‐performance liquid chromatography and its application

We developed a sensitive and robust electrogenerated chemiluminescence (ECL) flow sensor based on Ru(bpy)₃²⁺ immobilized with a Nepem‐211 perfluorinated ion exchange conductance membrane, which has robustness and stability under a wide range of chemical and physical conditions, good electrical conductivity, isotropy and a high exchange capacity for immobilization of Ru(bpy)₃²⁺. The flow sensor has been used as a post‐column detector in high‐performance liquid chromatography for determination of erythromycin and clarithromycin in honey and pork, and tricyclic antidepressant drugs in human urine. Under optimal conditions, the linear ranges were 0.03–26 ng/μL and 0.01–1 ng/μL for macrolides and tricyclic antidepressant drugs, respectively. The detection limits were 0.02, 0.01, 0.01, 0.06 and 0.003 ng/μL for erythromycin, clarithromycin, doxepin, amitriptyline and clomipramine, respectively. There is no post‐column reagent addition. In addition to the conservation expensive reagents, the experimental setup was simplified. The flow sensor was used for 2 years with high sensitivity and stability. Copyright © 2013 John Wiley & Sons, Ltd.     

Simultaneous determination of isoniazid and p‐aminosalicylic acid by capillary electrophoresis using chemiluminescence detection

It was found that isoniazid (ISO) or p‐aminosalicylic acid (PAS) could enhance the chemiluminescence (CL) emission from Cu (II)‐luminol‐hydrogen peroxide system, and the increased chemiluminescence signals were proportional to their concentrations, respectively. Based on this phenomenon, a chemiluminescence method coupled to capillary electrophoresis (CE) was established for simultaneous determination of ISO and PAS. The CE conditions including running buffer and running voltage were investigated in detail. The effects of the pH of H₂O₂ solution and the concentrations of luminol, H₂O₂ and Cu (II) on the CL signal were also investigated carefully. Under the optimized conditions, the analysis could be accomplished within 10 min, with the limits of detection of 0.3 µg mL^–1 for ISO and 1.1 µg mL^–1 for PAS, corresponding to 7.2 and 26.4 pg per injection (24 nL), respectively. Finally, the method was validated by determining the two analytes in pharmaceutical preparation and spiked human serum samples. The results of pharmaceutical tablet analysis were in good agreement with the labeled amounts. The recoveries for ISO and PAS in human serum were in the range of 92–104% and 90–113%, respectively. Copyright © 2009 John Wiley & Sons, Ltd.     

Highly sensitive chemiluminescence determination of tenoxicam using a cerium(IV)–sodium hyposulphite system in micellar medium

A simple, rapid and precise flow‐injection–chemiluminescence (FI–CL) method is presented for the determination of tenoxicam in pharmaceutical preparations and biological samples. The method is based on the weak chemiluminescence signal arising from the reaction of cerium(IV) in a nitric acid medium with sodium hyposulphite being significantly increased by tenoxicam in the presence of sodium dodecyl benzene sulphonate. Several experimental parameters affecting the CL reaction were examined and optimized systematically. Under the optimum conditions, the CL intensity was proportional to the concentration of tenoxicam in the range 7.0 × 10^–11–5.0 × 10^–8 g/mL. The detection limit was 2.3 × 10^–11 g/mL tenoxicam and the relative standard deviation (RSD) was 2.1% for 1.0 × 10^–9 g/mL tenoxicam solution (n = 11). The proposed method was applied to the determination of tenoxicam in pharmaceutical preparations, serum and human urine, with satisfactory results. The possible mechanism of the chemiluminescence reaction is also briefly discussed. Copyright © 2011 John Wiley & Sons, Ltd.     

Chemiluminescent derivatization of adenyl compounds with glyoxal derivatives in the presence of heteropoly acids and its application to the simple and sensitive determination of DNA

A chemiluminescence (CL) determination of adenyl compounds is described. CL derivatization of adenyl compounds with methylglyoxal dimethyl acetal was performed in the presence of tungstosilicic acid and propan-2-ol. CL from adenyl compounds was produced by hydrogen peroxide and L -cysteine ethyl ester in DMF and water. The proposed method is highly sensitive and specific to compounds containing adenine. Adenine was determined in the range 1.0 × 10⁻³ −5.0 × 10⁻⁸ M with the detection limit of 3.0 × 10⁻⁸ M (150 fmol per assay). The method was applied to the determination of DNA and detection limits of a few nanograms of DNA achieved. © 1998 John Wiley & Sons, Ltd.     

Perturbation of the tris(2,2′‐bipyridine) ruthenium(II)‐catalyzed Belousov–Zhabotinsky oscillating chemiluminescence reaction by l‐cysteine and its application

Perturbation of the tris(2,2′‐bipyridine)ruthenium(II) [Ru(bpy)₃²⁺]‐catalyzed Belousov–Zhabotinsky (BZ) oscillating chemiluminescence (CL) reaction induced by l ‐cysteine was observed in the closed system. It was found that the CL intensity was decreased in the presence of l ‐cysteine. Meanwhile, oscillation period and oscillating induction period were prolonged. The sufficient reproducible induction period was used as parameter for the analytical application of oscillating CL reaction. Under the optimum conditions, the changes in the oscillating CL induction period were linearly proportional to the concentration of l ‐cysteine in the range from 8.0 × 10^?7 to 5.0 × 10^?5 mol L^?1 (r = 0.997) with a detection limit of 4.3 × 10^?7 mol L^?1. The possible mechanism of l ‐cysteine perturbation on the oscillating CL reaction was also discussed. Copyright © 2009 John Wiley & Sons, Ltd.     

High‐throughput method for the analysis of venlafaxine in pharmaceutical formulations and biological fluids,using a tris(2,2′‐bipyridyl) ruthenium(II)–peroxydisulphate chemiluminescence system in a two‐chip device

A simple, rapid and sensitive chemiluminescent (CL) method for the assay of venlafaxine (VEN) in pharmaceutical formulations and serum samples by a two‐chip device is proposed. The method is based on the reaction of this drug with a tris(2,2′‐bipyridyl) ruthenium(II)–peroxydisulphate CL system. The optimum chemical conditions for CL emission were investigated. The calibration graph was linear for the concentration range 0.02–8.0 µg/mL. The detection and quantification limits were found to be 0.006 and 0.018 µg/mL, respectively, while the relative standard deviation (RSD) was <2.0%. The present CL procedure was applied to the determination of VEN in pharmaceutical formulations and serum samples; the recovery levels were in the range 96.5–101.2%. The results suggest that the method is unaffected by the presence of common formulation excipients found in these samples. Copyright © 2012 John Wiley & Sons, Ltd.