Development of a "turn off" fluorescent molecularly imprinted nanoparticle-based sensor for selective captopril quantification in synthetic urine and wastewater samples.

The combination of silica nanoparticles with fluorescent molecularly imprinted polymers (Si-FMIPs) prepared by a one-pot sol-gel synthesis method to act as chemical sensors for the selective and sensitive determination of captopril is described. Several analytical parameters were optimized, including reagent ratio, solvent, concentration of Si-FMIP solutions, and contact time. Fourier-transform infrared spectroscopy (FT-IR), transmission electron microscopy (TEM), and the ninhydrin assay were used for characterization. The selectivity was evaluated against molecules belonging to other drug classes, such as fluoroquinolones, nonacid nonopioids, benzothiadiazine, alpha amino acids, and nitroimidazoles. Under optimized conditions, the Si-FMIP-based sensor exhibited a working range of 1-15 µM, with a limit of detection (LOD) of 0.7 µM, repeatability of 6.4% (n = 10), and suitable recovery values at three concentration levels (98.5% (1.5 µM), 99.9% (3.5 µM), and 99.2% (7.5 µM)) for wastewater samples. The sensor provided a working range of 0.5-15 µM for synthetic urine samples, with an LOD of 0.4 µM and a repeatability of 7.4% (n = 10) and recovery values of 93.7%, 92.9%, and 98.0% for 1.0 µM, 3.5 µM, and 10 µM, respectively. In conclusion, our single-vessel synthesis approach for Si-FMIPs proved to be highly effective for the selective determination of captopril in wastewater and synthetic urine samples.

2D-Single-crystal hexagonal gold nanosheets for ultra-trace voltammetric determination of captopril.

Two dimensional single-crystal hexagonal gold nanosheets (SCHGNSs) were prepared by microwave heating of a solution of HAuCl4 in an ionic liquid. The SCHGNSs were characterized by field emission electron microscopy, energy-dispersive X-ray spectroscopy, X-ray diffraction, atomic force microscopy and electrochemical impedance spectroscopy. The SCHGNSs were then used to modify a graphite paste electrode for voltammetric determination of the hypertension drug captopril (CAP). The modified electrode showed a well-defined oxidation peak (at 0.41 V vs. Ag/AgCl) at pH 7.0 using differential pulse voltammetry. Under the optimum conditions, the response is linear in the 2-400 nM and 4.0-50 µM CAP concentration range, and the detection limit (at S/N = 3) is 0.3 nM. The sensor was successfully applied to the determination of CAP in pharmaceutical tablets and in spiked urine. Graphical abstract Schematic presentation of the preparation of single crystal hexagonal gold nanosheets and their use to modify a carbon paste electrode for ultra-trace voltammetric determination of the drug captopril.

Turn-on fluorescent detection of captopril in urine samples based on hydrophilic hydroxypropyl ß-cyclodextrin polymer.

Here, one kind of hydrophilic hydroxypropyl ß-cyclodextrin cross-linked polymer (HP-CDP) was prepared and used to establish a "turn-on" fluorescent probe for selective determination of captopril in biological samples. The HP-CDP has been synthesized in one step by cross-linking (2-hydroxypropyl)-ß-cyclodextrin (HP-ß-CD) with a rigid aromatic group linker tetrafluoroterephthalonitrile (TFT), and the synthesis parameters of HP-CDP were optimized with water solubility, yield, and adsorption capacity as indicators. When it was used as a luminescent material, we have found an interesting phenomenon that the fluorescence emission of HP-CDP was quenched after forming a coordination compound with ferric ions, and then recovered after adding a certain concentration of captopril, since captopril can reduce the ferric iron to ferrous ions and cause ligand replacement. Based on this observation, a novel turn-on fluorescent method was developed for the determination of captopril. The method exhibited good linearity in the range of 9.2 × 10-7 to 4.6 × 10-4 M (R2 = 0.9982) and a low detection limit of 1.8 × 10-7 M at optimum HP-CDP concentration, ferric ion concentration, pH, and incubation time. Moreover, interference experiments demonstrated that this fluorescence sensor had excellent selectivity that can commendably resist the interference from potential foreign substances. The proposed method has been successfully applied to determine captopril in human urine samples and may provide outstanding application potential in the future development of sensors. In addition, it is believed that HP-CDP also has a wide range of applications, for example, as a solubilizer, pollutant adsorbent, or drug carrier. Graphical abstract ᅟ.

Smartphone application for captopril determination in dosage forms and synthetic urine employing digital imaging.

A simple, accurate, and low-cost analytical procedure for captopril determination through digital imaging is presented. The method relies on the spot test reaction between captopril and palladium (II) chloride, which produces a yellow and water-soluble complex with maximum absorption at 380 nm. A smartphone camera and a portable apparatus built for internal lighting control were put together to acquire digital images of reaction mixtures. Digital image processing through the RGB approach was used to establish a quantitative relationship between color intensity and captopril concentration. Under the most suitable operational and experimental conditions, an analytical curve was built monitoring the Blue channel within the concentration range of 3.12 × 10-5 to 1.21 × 10-3 mol L-1. Limits of detection and quantification were equal to 8.06 × 10-6 and 2.69 × 10-5 mol L-1, respectively. Recovery percentage in synthetic urine samples ranged from 97.1% to 102.9%. Results were compared with a reference method and no significant differences were detected at the 95% confidence level. The developed method presents budgetary and environmental advantages concerning the use of cheap and easy-handled devices and the consumption of very low volumes of reagent (800 µL per determination). It can be a useful analytical tool for laboratories with limited financial resources while abiding by green chemistry principles.

Captopril apparently increase and cisplatin apparently decrease human albumin concentration in artificial urinary solutions.

BACKGROUND: Measurement of urinary albumin (HSA) is very important in diagnostic of kidney diseases. Much less is known about the possible impact of substances present in urine together with albumin on the results of measurements. METHODS: We investigated the effect of the presence of captopril and cisplatin in the solution on the result of the determination of HSA by native polyacrylamide gel electrophoresis. Protein conformation in the absence and presence of the drugs was examined using Fourier Transform Infrared Spectroscopy (FTIR). RESULTS: The presence of captopril apparently increases HSA concentration while cisplatin causes an apparent decrease in the HSA concentration. The presence of both drugs also influence the secondary structure forms of HSA albumin investigated by FTIR. CONCLUSION: Both drugs tested in the concentration of human use can have an impact on the results of determination of albumin in urine which can influence clinical decision.

Permanganate-bromide-silver nanoparticles as a new chemiluminescence system and its application to captopril determination.

A novel chemiluminescence (CL) system based on the oxidation of bromide by permanganate in sulfuric acid medium is introduced. The enhancing effect of silver nanoparticles (NPs), synthesized by chemical reduction method, on this reaction was studied. It was demonstrated that spherical silver nanoparticles with average size of 18 nm had a most remarkable catalytic effect on this reaction. CL emission wavelengths and UV-vis spectra were used to characterize the system and propose a possible mechanism. Furthermore, it was found that captopril inhibits the action of NPs and decreases the intensity of CL. Based on this phenomenon, a new CL method was developed for the determination of captopril in the 3.0 × 10(-10) to 1.0 × 10(-7) mol L(-1) concentration range with a detection limit (3s) of 0.12 nmol L(-1). The method was successfully applied to the determination of captopril in pharmaceutical formulations, human urine and serum samples.

RP-HPLC-UV method coupled with post-column iodine-azide reaction for determination of free captopril in urine samples.

BACKGROUND: A free urinary captopril is measured indirectly employing the iodine-azide reaction in post-column mode. The pre-clean-up and/or derivatization step is needless, so that the method is adequate for rapid captopril determination in the urine samples and its monitoring at clinical trial. Captopril is separated on a C4 column by the eluate composed of sodium azide solution (4% [w/v], pH 5.8), acetonitrile and water at a ratio of 50:5:45 (v/v/v). The linearity exists in the range from 0.06 to 2.25 µmol/ml of urine. LOD and LOQ receive 0.03 and 0.06 µmol/ml of urine, respectively. RESULTS: Inter-day precision and accuracy of measurements of the captopril-spiked urine samples were 9, 8 and 5%, and 104, 107 and 105%, respectively, for 0.060 (low level), 0.50 (medium level) and 1.25 (high level) µmol/ml of urine. CONCLUSION: Captopril content was determined in real urine samples delivered from patients treated with this drug.

Spectral characteristic investigation on complex of Ni (II) with captopril and its analytical application.

In this paper, Ni (II) reacting with captopril (CPT) can form complex in alkaline solution and the formed complex has a characteristic absorption peak at 340nm. The absorbance of the Ni-CPT complex increases linearly with the increased concentration of captopril. The study also shows that ammonia has an obvious sensitizing effect on the absorbance. Based on the study, a new method for the determination of captopril is established. Experimental results show that the linear range of this method under optimum condition is 1.0-60mg/L with correlation coefficient, detection limit and precision of 0.9999, 0.31mg/L and 0.87%, respectively. The method used to determine captopril in commercial captopril tablets has a satisfactory result with the recoveries in the range of 99.0-103.6% and the relative standard deviation (RSD) in the range of 0.8-3.7%. We preliminarily study the reaction mechanism and demonstrate that the complex ratio of Ni (II) with captopril is 1:2 and the formation constant is 6.3×10(9).

The new approach for captopril detection employing triangular gold nanoparticles-catalyzed luminol chemiluminescence.

In this work, we utilize the triangular gold nanoparticles (AuNPs) prepared by trisodium citrate reduction of HAuCl(4) in presence of nonionic fluorosurfactant (FSN) as a novel chemiluminescence (CL) probe for the determination of captopril. Captopril can induce a sharp decrease in CL intensity from the triangular AuNPs-catalyzed luminol system. Under the selected experimental conditions, a linear relationship was obtained between the logarithm of CL intensity and the logarithm of concentration of captopril in the range of 23.0-920 nM, and the detection limit at a signal-to-noise ratio of 3 for captopril was 4.6 nM. The as-prepared triangular AuNPs were easier to synthesize, stable at a wider pH range and high ionic strength, and exhibited a high selectivity and an excellent sensitivity toward captopril. The applicability of the proposed method has been validated by determining captopril in commercial pharmaceutical formulations and human urine samples with satisfactory results. The recoveries for captopril in spiked samples were found to be between 95.0% and 103.5%. The method shows promise for routine control analysis of pharmaceutical preparations and human urine samples. Moreover, based on the CL spectra, UV-vis spectra and transmission electron microscope (TEM) measurements, a possible CL mechanism was proposed. The mechanism of high selectivity toward captopril is supposed to originate from the tight binding of the sulphydryl groups of captopril to the active site of the as-prepared triangular AuNPs, leading to oxygen-related radicals cannot easily be generated from H(2)O(2) on the surface of triangular AuNPs.

Automated determination of total captopril in urine by liquid chromatography with post-column derivatization coupled to on-line solid phase extraction in a sequential injection manifold.

The present study reports a new liquid chromatographic (HPLC) method for the determination of the anti-hypertension drug captopril (CAP) in human urine. After its separation from the sample matrix in a reversed phase HPLC column, CAP reacts with the thiol-selective reagent ethyl-propiolate (EP) in a post-column configuration and the formed thioacrylate derivative is detected at 285 nm. Automated 4-fold preconcentration of the analyte prior to analysis was achieved by an on-line solid phase extraction (SPE) step using a sequential injection (SI) manifold. The Oasis HLB SPE cartridges offered quantitative recoveries and effective sample cleaning by applying a simple SPE protocol. The limits of detection and quantitation were 10 µg L(-1) and 35 µg L(-1) respectively. The percent recoveries for the analysis of human urine samples ranged between 90 and 96% and 95 and 104% using aqueous and matrix matched calibration curves respectively.

Highly sensitive voltammetric sensor based on catechol-derivative-multiwall carbon nanotubes for the catalytic determination of captopril in patient human urine samples.

A new catechol-derivative compound, N-(3,4-dihydroxyphenethyl)-3,5-dinitrobenzamide, was synthesized and used to construct a modified-carbon nanotubes paste electrode. The electro-oxidation of captopril at the surface of the modified electrode was studied using cyclic voltammetry, chronoamperometry, and electrochemical impedance spectroscopy. Under the optimized conditions, the differential pulse voltammetric peak current of captopril increased linearly with captopril concentration in the ranges of 6.4×10(-8) to 3.2×10(-48) mol L(-1). The detection limit was 3.4×10(-8) mol L(-1) captopril. The diffusion coefficient and kinetic parameters (such as electron transfer coefficient and the heterogeneous rate constant) for captopril oxidation were also determined. The RSD% for 0.5 and 10.0 µmol L(-1) captopril were 2.1% and 1.6%, respectively. The proposed sensor was successfully applied for the determination of captopril in human patient urine and tablet samples.

Quantification of captopril in urine through surface-assisted laser desorption/ionization mass spectrometry using 4-mercaptobenzoic acid-capped gold nanoparticles as an internal standard.

We have developed a new internal standard method for the determination of the concentration of captopril (CAP) through surface-assisted laser desorption/ionization mass spectrometry (SALDI-MS) using gold nanoparticles (Au NPs). This approach provided linearity for CAP over the concentration range 2.5-25 microM (R(2) = 0.987), with a limit of detection (signal-to-noise ratio = 3) of 1.0 microM. The spot-to-spot variations in the concentration of CAP through SALDI-MS analyses performed in the absence and presence of the internal standard were 26% and 9%, respectively (15 measurements). This approach provides simplicity, accuracy, precision, and great reproducibility to the determination of the levels of CAP in human urine samples.

Parafac and PLS applied to determination of captopril in pharmaceutical preparation and biological fluids by ultraviolet spectrophotometry.

A new ultraviolet spectrophotometric method has been developed for the direct qualitative determination of captopril in pharmaceutical preparation and biological fluids such as human plasma and urine samples. The method was accomplished based on parallel factor analysis (PARAFAC) and partial least squares (PLS). The study was carried out in the pH range from 2.0 to 12.8 and with a concentration from 0.70 to 61.50 microg ml(-1) of captopril. Multivariate calibration models PLS at various pH and PARAFAC were elaborated from ultraviolet spectra deconvolution and captopril determination. The best models for this system were obtained with PARAFAC and PLS at pH = 2.04 (PLS-PH2). The applications of the method for the determination of real samples were evaluated by analysis of captopril in pharmaceutical preparations and biological (human plasma and urine) fluids with satisfactory results. The accuracy of the method, evaluated through the root mean square error of prediction (RMSEP), was 0.58 for captopril with PARAFAC and 0.67 for captopril with PLS-PH2 model. Acidity constant of captopril at 25 degrees C and ionic strength of 0.1 M have also been determined spectrophotometrically. The obtained pKa values of captopril are 3.90 +/- 0.05 and 10.03 +/- 0.08 for pKa. and pKa2, respectively.

Development and validation of a capillary electrophoresis method with laser-induced fluorescence detection for the determination of captopril in human urine and pharmaceutical preparations.

This study describes the development of a CE method for the analysis of the antihypertensive drug captopril using LIF detection. The method is based on the derivatization of captopril with the fluorescent label 5-iodoacetamidofluorescein. The optimization of the electrophoretic electrolyte composition together with other variables, such as applied voltage and injection time, resulted in a solution of 20 mM phosphate buffer adjusted to pH 12.0. The calibration curve for the fluorescent captopril derivative was linear in the concentration range 3.5-6000 ng/mL with a detection limit of 0.5 ng/mL. Intra- and interday precision (at a concentration of about 100 times the LOD) were less than 0.86 and 1.16%, respectively, both expressed as RSD. The assay was successfully used for quantification of captopril in some marketed pharmaceutical preparations and urine samples.

A study of the determination of the hypertensive drug captopril by square wave cathodic adsorptive stripping voltammetry.

In this work, the determination of captopril (CPL) was studied by square wave cathodic adsorptive stripping voltammetry (SWCAdSV) on a hanging mercury drop electrode (HMDE). CPL was adsorptively preconcentrated on the mercury surface as a sparingly soluble mercury salt under stirring of the solution and then the accumulated species was reduced by a cathodic square wave voltammetric scan. The reduction current was related to the CPL concentration in the sample. The chemical and instrumental parameters affecting the response were investigated and optimized for the CPL determination. The calibration curve was linear from 0.5 to 180 microg l(-1) of CPL (depending on the preconcentration time), the limit of detection at a S/N ratio of 3 was 0.5 microg l(-1) with 300 s of preconcentration and the relative standard deviation was 3.2% at the 20 microg l(-1) level (with 120 s of preconcentration, n=8). The method was applied to the determination of CPL in two pharmaceutical formulations with recoveries of 97.9 and 98.8%. Finally, the potential for applying the proposed method to the determination of CPL in biological media is briefly discussed.

3-Bromomethyl-propyphenazone as a new derivatization reagent for high performance liquid chromatography of captopril and hydrochlorothiazide with UV-detection.

3-Bromomethyl-propyphenazone (BMP) was used as a derivatization reagent for the detection and quantification of captopril (CAP) and hydrochlorothiazide (HCT) by high performance liquid chromatography using Zorbax C8 column, and 0.05M sodium acetate, acetonitrile, methanol (14:17:4; pH 6.5) as mobile phase system with UV-detection at 254 nm. The cited reagent reacts with the mercapto and amino groups of CAP and HCT in acetone using anhydrous potassium carbonate as hydrobromide acceptor. The reaction was completed within 30 min for CAP and 60 min for HCT with heating at 105 +/- 5 degrees C in mini-reaction vial. The linear concentration ranges for both CAP and HCT were 8 to 160 and 6 to 140 ng per injection, respectively. The derivatized captopril was synthesized and confirmed with spectral analysis. This method was applied for determination of spiked captopril in human urine after extraction with Extrelut-20 column using ethyl acetate:isopropanol (85:15 v/v) as eluant.

Determination of captopril and its disulphides in whole human blood and urine by high-performance liquid chromatography with ultraviolet detection and precolumn derivatization.

An assay that measures the total, and protein-bound captopril, the orally active antihypertensive drug, in whole human blood and urine has been developed. The procedure involves a precolumn derivatization of the drug via its sulfhydryl group with 1-benzyl-2-chloropyridinium bromide followed by solid-phase extraction and reversed-phase high-performance liquid chromatography separation with ultraviolet detection at 314 nm. Oxidized and protein-bound captopril is converted to reduced form by the use of triphenylphosphine and derivatized and quantified in the same manner. The proposed method offers the possibility of determining the in vivo redox status of captopril in blood of patients orally given a standard dose of at least 12.5 mg of captopril as part of the treatment of hypertensive disease and/or congestive heart failure. In the recommended procedure the sulfhydryl form of captopril is trapped with minimal oxidation by derivatizing blood samples at the time of collection. This is attained by drawing blood directly into tubes containing solutions of 1-benzyl-2-chloropyridinium bromide. The method enables also the determination of urinary excretion of captopril and its disulphides after oral administration of the drug. Accurate determinations are possible over a concentration range of 10 to 500 ng/ml captopril in blood, 50 to 1200 ng/ml captopril in urine and 10 to 1000 ng/ml captopril disulphide and 50 to 3000 ng/ml captopril disulphide in blood and urine, respectively. The detection and quantification limits for both blood and urine are 0.3 and 10 ng/ml, respectively.

Simple high-performance liquid chromatographic method for the determination of captopril in biological fluids.

A rapid, simple and sensitive column-switching high-performance liquid chromatographic procedure for the determination of captopril in plasma and urine had been developed. p-Bromophenacyl bromide was used as a derivatizing reagent to react with captopril to form a product that showed ultraviolet-absorbing properties. For plasma samples the protein was removed with 6% perchloric acid before injection. The urine samples were directly injected into the chromatograph. The column-switching system was equipped with a pre-column (5 cm x 0.5 cm I.D.) packed with muBondapak C18 (37-50 microns) and an analytical column (15 cm x 0.5 cm I.D.) packed with YWG-C18, 10 microns. Impurities were washed from the pre-column with 0.2% acetic acid and the retained substances were eluted into the analytical column with acetonitrile-water-acetic acid (35:65:0.4, v/v). Captopril was detected at 260 nm. The calibration curve was linear in the range 20-1000 ng/ml for plasma and 10-200 micrograms/ml for urine. The recoveries averaged 103.2 and 99.5% for plasma and urine, respectively. The coefficients of variation were all less than 10%.

[Determination of captopril in plasma and urine by high-performance liquid chromatography with column switching].

A rapid and sensitive column-switching high performance liquid chromatographic procedures was described for determination of captopril in plasma and urine. p-Bromophenacyl bromide, a derivatizing reagent, was added to the plasma and urine samples to form an adduct which showed ultraviolet absorbing properties. After that, the urine sample was injected directly and for plasma the protein was removed with 6% of perchloride before injection. The column-switching system was equipped with a pre-column of 5 cm x 0.5 cm ID, packed with mu Boundapak C18, 37-50 microns, and an analytical column of 15 cm x 0.5 cm ID, packed with YWG-C18, 10 microns. After washing out the impures from pre-column with 0.2% acetic acid the retained substances were eluted into analytical column with acetonitrile-water-acetic acid (35:65:0.4). Captopril was detected at 260 nm. The method was linear within 20-1000 ng/ml for plasma and 10-200 micrograms/ml for urine. The recovery averaged 103.2% and 99.5% for plasma and urine, respectively. The coefficient variations were all less than 10%.