Sensitive Analytical Procedure Research Articles

Assessment and modifications of digestion procedures to determine trace elements in urine of hypertensive and diabetes mellitus patients

Context: There is accumulating evidence that the metabolism of several trace elements like Cr, Cu, Pb, Cd, Co, Mn and Zn might have specific roles in the pathogenesis and progress of many diseases like hypertension (HTN) and diabetes mellitus (DM). Objectives: To provide a fast, efficient, sensitive, and reliable analytical procedure for trace element determination in urine samples of HTN and DM patients using inductively coupled plasma optical emission spectrometry (ICP-OES). Setting and Design: The ICP-OES operating conditions were optimised and carefully selected in order to maximise the sensitivity, precision and accuracy. Factors affecting analytical and biological variability of the concentrations under study were discussed and carefully optimised. Materials and Methods: Different digestion procedures with acids and oxidising reagents were tested. The suitable procedure ICP-OES was selected, carefully modified and applied. The validity and accuracy of the different elements were determined by spiking of samples with known amounts of multi-element standard solution. Statistical Analysis: Student t-test and analysis of variance (ANOVA) test were used for analysis. Microsoft Excel was used to assess the significance of the difference between variables. The concentrations obtained were expressed as mean value ± standard deviation (P = 0.05). Results: The results of this study showed that the mean concentrations of Cd, Zn, Pb, Cu, Cr and Mn in urine from both HTN (study group A) and DM (study group B) patients were higher than the corresponding values observed in the control group. However, while the mean value of Co was low as compared to the control group, the differences found were not significant (P = 0.05). Conclusion: The method used had excellent sensitivity, multi-element data could be obtained with very short acquisition time. The elements Cr, Cd, Pb and Zn might have specific roles in the pathogenesis and progress of HTN and DM. Further studies are required to investigate the possible roles of these elements in HTN and DM individuals.

New Developments in Liquid Chromatography Mass Spectrometry for the Determination of Micropollutants

The combination of liquid chromatography (LC) with mass spectrometry (MS) in the environmental field has appeared as a valuable tool for the determination of micropollutants. Several groups of compounds have been considered as particularly relevant (e.g., pharmaceuticals, hormones and other endocrine-disrupting, personal care products and their metabolites, flame retardants, surfactants, and plasticizers, among others) since the same ones are continuously being released in the environment mainly as a result of the manufacturing processes, the disposal of unused or expired products, and the excreta. Because these micropollutants are not completely removed in the environment, very specific and sensitive analytical procedures are needed for their identification and quantification. High performance liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) (or LC-MS2) and especially time-of-flight mass spectrometry (TOF/MS), has allowed that many environmental contaminants that are highly polar or nonvolatile or have a high molecular weight to be analyzed or identified. In this work we present an overview focused on the developments of liquid chromatography mass spectrometry applied to the analysis of the main classes of micropollutants in aqueous and solid environmental samples. Various aspects of methodologies based on these techniques, including sample preparation (extraction/preconcentration) and matrix effects, are discussed.

On-line solid-phase enrichment coupled to packed reactor flow injection analysis in a green analytical procedure to determine low levels of folic acid using fluorescence detection

BackgroundAnalysis of folic acid (FA) is not an easy task because of its presence in lower concentrations, its lower stability under acidic conditions, and its sensitiveness against light and high temperature. The present study is concerned with the development and validation of an automated environmentally friendly pre-column derivatization combined by solid-phase enrichment (SPEn) to determine low levels of FA.ResultsCerium (IV) trihydroxyhydroperoxide (CTH) as a packed oxidant reactor has been used for oxidative cleavage of FA into highly fluorescent product, 2-amino-4-hydroxypteridine-6-carboxylic acid. FA was injected into a carrier stream of 0.04 M phosphate buffer, pH 3.4 at a flow-rate of 0.25 mL/min. The sample zone containing the analyte was passed through the CTH reactor thermostated at 40°C, and the fluorescent product was trapped and enriched on a head of small ODS column (10 mm x 4.6 mm i.d., 5 μm particle size). The enriched product was then back-flush eluted by column-switching from the small ODS column to the detector with a greener mobile phase consisting of ethanol and phosphate buffer (0.04M, pH 3.4) in the ratio of 5:95 (v/v). The eluent was monitored fluorimetrically at emission and excitation wavelengths of 463 and 367 nm, respectively. The calibration graph was linear over concentrations of FA in the range of 1.25-50 ng/mL, with a detection limit of 0.49 ng/mL.ConclusionA new simple and sensitive green analytical procedure including on-line pre-column derivatization combined by SPEn has been developed for the routine quality control and dosage form assay of FA at very low concentration level. The method was a powerful analytical technique that had excellent sensitivity, sufficient accuracy and required relatively simple and inexpensive instrumentation.

A new approach for antibiotic drugs determination in human plasma by liquid chromatography–mass spectrometry

Sensitive and selective analytical procedures based on high performance liquid chromatography with mass spectrometric detection were developed for the determination of linezolid (LIN) and amoxicillin (AMOX) in human plasma samples. Samples were prepared by applying protein precipitation (PP), solid phase extraction (SPE), and microextraction in packed syringe (MEPS). The analytical separation was carried out using reversed phase liquid chromatography in isocratic mode. All analytes were monitored by mass spectrometry (MS) detection in the product ion mode and the method was validated covering the corresponding therapeutic range of 1–30μg/mL and 1–50μg/mL for LIN and AMOX respectively. The assay was linear over AMOX and LIN concentration ranges. The method provided good validation data: accuracy (102.9% (LIN), 100.9% (AMOX)), limit of detection (0.1407ng/mL (LIN); 0.1341ng/mL (AMOX); quantification (0.3814ng/mL (LIN), 0.4249ng/mL (AMOX)) and acceptable stability within 24h in the auto-sampler. Three different methods were compared as regards precision, accuracy, recovery and matrix effects. The proposed methods offer a fast and simple way to determine selected antibiotic drugs in human plasma that could be applied in pharmacokinetic studies.

Applying second-order adjoint perturbation theory to time-dependent problems

In this paper we discuss the application of second-order adjoint based perturbation techniques to linear and nonlinear time dependent problems. These techniques are based on the property of the adjoint problem which allows calculating the set of first and second order coefficients by solving a number of adjoint systems.The derivation of a second order adjoint theory that can be used to calculate the second order Taylor components of a functional response is first presented for nonlinear problems, and then reformulated for linear systems. This implementation is based on the Adjoint Sensitivity Analysis Procedure, originally presented by Cacuci.The theoretical part is followed by the application of the technique to some classical reactor physics problems: a fuel depletion calculation, a linear and a nonlinear point-kinetic problem.The results obtained using the second order theory are compared with the values obtained using a first order approximation and a direct solution of the forward problem. Our first results show that the procedure provides good estimations in presence of higher order perturbation components, being able to reconstruct the responses of interest even in presence of large perturbations. The main differences between linear and nonlinear formulations and their computational implications are also discussed.

Reliability Based Buckling Analysis of Composite Panels with Tophat Stiffened Topology

A reliability based analysis method for composite panels with tophat stiffened topology was presented in this paper. An energy based grillage method was developed for the buckling problems of the stiffened panels subject to bi-directional in-plane loads. The variables that have large impact on structural safety were identified using a sensitivity analysis procedure. The coupling effects of the plate dimension ratio and in-plane loading ratio on the critical buckling loads were investigated.

On-line coupling of derivatization with pre-concentration to determine trace levels of methotrexate

A new simple, sensitive and precise green analytical procedure using an automated packed-reactor derivatization technique coupled with on-line solid-phase enrichment (SPEn) has been developed and evaluated to determine trace levels of methotrexate (MTX). The method was based on injection of MTX into a flowing stream of phosphate buffer (0.04M, pH 3.4), carried through the packed oxidant reactor of Cerium (IV) trihydroxyhydroperoxide for oxidative cleavage of the drug into highly fluorescent product, 2,4-diaminopteridine-6-carboxylic acid, followed by SPEn on a head of short ODS column (10mm×4.6mm i.d., 5μm particle size). The flow rate was 0.25mL/min and packed reactor temperature was 40°C. The trapped product was back-flush eluted from the ODS column to the detector by column-switching with an environmentally friendly mobile phase consisting of ethanol and phosphate buffer (0.04M, pH 3.4) in the ratio of 5:95 (v/v). The eluent was monitored at emission and excitation wavelengths of 460 and 360nm, respectively. The calibration curve was linear over the concentration range of 1.25–50ng/mL with a detection limit of 0.08ng/mL. The method was successfully applied to determine MTX in pharmaceutical formulations with mean percentage recovery ranging from 99.48 to 99.60.

A Parallel Krylov-Based Adjoint Sensitivity Analysis Procedure

We have implemented the first-order adjoint sensitivity analysis procedure (ASAP) into the three-dimensional parallel radiation transport code system Denovo, a module of the SCALE software suite. In particular, we used a Krylov-based approach to compute the solution to the inhomogeneous adjoint systems occurring in the ASAP. Our implementation, as a component of Denovo’s scalable framework, should allow the efficient computation of cross section and atomic number density sensitivity coefficients for critical systems in a massively parallel fashion. We have constructed a proof that the Krylov-based approach converges to a unique solution and compared its computational requirements with the standard algorithm used in the neutron transport community. In addition, we performed a verification of our ASAP implementation on the Godiva experimental benchmark. We found the new approach to be an order of magnitude faster than the standard algorithm in this benchmark.

A sensitive spectrophotometric determination of atrazine in micellar medium and its application in environmental samples

A sensitive analytical procedure based on solid phase extractive-spectrophotometry has been established for the determination of the widely used herbicide atrazine .The method is based on the Konig reaction in which atrazine reacts with pyridine reagent to form a quaternary pyridinium halide, which further forms glutaconic aldehyde in the presence of alkali. Glutaconic aldehyde is subsequently coupled with 4-aminoacetanilide in the micellar medium of anionic surfactant sodium dodecyl sulphate to give a yellow-orange dye. The produced dye was enriched on a C18 cartridge and is measured spectrophotometrically at 460 nm. The sensitivity and selectivity of the method was largely enhanced in the micellar media and SPE on the C18 cartridge and avoids the use of toxic solvents. Beer’s law was obeyed in the range 0.012–0.12 μg mL−1. Molar absorptivity and Sandell’s sensitivity were found to be 1.52 × 106 L mol− 1 cm−1 and 0.0002 μg cm−2, respectively. The limit of detection and quantification were 0.001 and 0.003 μg mL−1, respectively. The proposed method was applied successfully for the determination of atrazine in environmental and biological samples with a recovery range of 96–101 %. The method was found to be free from interference of a large number of foreign species. The accuracy and reliability of the method was further established by parallel determination by the reference method, and by recovery studies.

Fatal Metformin Intoxication with Markedly Elevated Blood and Liver Concentrations

The highest postmortem metformin concentrations are recorded utilizing a sensitive and specific analytical procedure. The peripheral blood metformin concentration was 240 mg/L, the liver concentration was 240 mg/kg and the gastric concentration was 1,700 mg. Additionally, an antemortem blood sample collected shortly after admission revealed a metformin concentration of 210 mg/L. These data, revealing a liver to peripheral blood ratio of 1.0, provide additional support that metformin is not subject to postmortem redistribution. Intentional self-poisonings with metformin can result in death, despite multiple medical interventions.

Simultaneous determination of Solvent Yellow 124 and Solvent Red 19 in diesel oil using fluorescence spectroscopy and chemometrics

Differences in tax levels for diesel oil stimulate the illegal removal of characteristic diazo compounds purposely added to designate its possible usage. In order to reduce the losses in the national income, there is a strong need to develop a sensitive and cost-effective analytical procedure for the detection of this illegal action. In this study, we describe a novel analytical approach for a qualitative and quantitative determination of two diazo compounds (Solvent Yellow 124 and Solvent Red 19) that are usually added to diesel oil. The methodology proposed combines the use of excitation–emission matrix fluorescence spectroscopy as an analytical technique and partial least squares regression as a multiple modeling tool. With this new methodology, relatively low root mean square errors of prediction (for independent set of test samples) that are equal to 0.223 for Solvent Red 19 and 0.263 for Solvent Yellow 124, were obtained and the results were stable, which were indicated by an analysis performed after 48 and 96h. The methodology is also nondestructive and allows for (i) simultaneous detection of diesel oil additives, (ii) determination of satisfactory limits of detection (0.048 and 0.042mgL−1 for Solvent Red 19 and Solvent Yellow 124, respectively), and (iii) obtaining of considerably low relative standard deviations of 2.33% for Solvent Yellow 124 and of 3.23% for Solvent Red 19 in comparison with the existing norm level.

Simultaneous Determination of Trace Antimony and Bismuth in Jilin Ginseng with Microwave Digestion Hydride Generation Atomic Fluorescence Spectrometry

A robust, accurate and sensitive analytical procedure was developed for the simultaneous determination of trace Antimony and Bismuth in Jilin ginseng by hydride generation atomic fluorescence spectrometry. The parameters were studied systematically, such as acid concentration of the reaction medium, flow rate of the carrier gas and shield gas, the atomizer of height, etc. Ascorbic acid and thiourea were used as reducer or masking agents to enhance the generation efficiency of the volatile species of Sb and Bi. In the presence of thiourea and ascorbic acid, the influences of some coexisting elements on the determination of antimony and bismuth were investigated.

Nonlinear Analysis and Optimum Design of Guyed Masts

In this paper the nonlinear analysis and design optimization of guyed masts is addressed. The mast is modeled as a 3D truss and is supported by catenary cable elements that have nonlinear elastic behavior. For nonlinear static analysis, an innovative procedure is proposed that divides the structure into linear and nonlinear parts and analyzes them separately. The proposed method satisfies the equilibrium and compatibility by establishing and solution of a set of nonlinear equations. The optimization problem employs the sizes of members, initial cable tensions and the positions of anchor on the ground and tie level of cables on the mast as design variables. To facilitate the optimization solution, a compatible sensitivity analysis procedure is proposed. Sensitivities of objective function, displacement and strength constraints in the mast and cables, subjected to a variety of load combinations including dead, wind and ice loads are calculated. Numerical examples are provided to show the nonlinear analysis procedure and the applicability of the algorithm to optimum design of practical guyed masts.

Efficient set-up for determination of elemental content in liquid samples using neutron activation analysis

A simple, sensitive and fast procedure for analysis of liquid samples called flowing sample neutron activation analysis has been established based on measurement of short-lived radionuclides. This newly developed method involves continuous flowing of sample between an irradiation cell and measurement station. This arrangement makes it easy to analyze a large volume of sample and thus preconcentration steps can be avoided. Moreover, flowing sample technique feeds detector with fresh irradiated material, which maintains constant dead time during whole time of measurement; hence improves accuracy of the method. The method was tested for its repeatability, detection limits and sensitivity. Obtained limits of detection are favorably comparable with those already published in literature.

Understanding the metabolism of urban-rural ecosystems

A Multi-sectoral Systems Analysis (MSA) methodology is presented as a tool for identifying the level of importance of flows of energy and materials (water, nitrogen, phosphorus, and carbon) as they pass through an anthropogenically manipulated system. That system comprises a web of processes, across a total of five industrial sectors: water, forestry, food, energy and waste management. Given the heterogeneous nature and quality of data sources, the propagation of data uncertainty is considered through a Regionalized Sensitivity Analysis (RSA) procedure, based on the Monte Carlo simulation approach. The MSA reveals the advantages of studying different material cycles simultaneously, in addition to interpreting them individually, while gaining insight into the magnitude of the associated flows. The proposed framework is illustrated for a case study of the Upper Chattahoochee Watershed, in which parts of Metro Atlanta are located. Results show that natural flows are predominant in the water and energy cycles. Direct human manipulations of water, i.e., withdrawals for public supply and power generation, are less than 25% of the amount received as precipitation. Solar input is 200 times the total demand for electricity. Apart from sun-light, gasoline for transportation is the flow with the largest content of energy; it is responsible for providing 71% of the total demand of fuels for uses other than power generation. In contrast, cycles of nutrients such as N and C are strongly related to the flows of fuels, mainly coal and natural gas. In a second tier, fertilizer use and the poultry industry in the region are significant for the use of nitrogen. Phosphorus fluxes are similarly dominated by the food sector and, as a consequence, to a lesser extent by the water sector, because of water’s role as a waste-conveyance medium.

Inferring robust gene networks from expression data by a sensitivity-based incremental evolution method

BackgroundReconstructing gene regulatory networks (GRNs) from expression data is one of the most important challenges in systems biology research. Many computational models and methods have been proposed to automate the process of network reconstruction. Inferring robust networks with desired behaviours remains challenging, however. This problem is related to network dynamics but has yet to be investigated using network modeling.ResultsWe propose an incremental evolution approach for inferring GRNs that takes network robustness into consideration and can deal with a large number of network parameters. Our approach includes a sensitivity analysis procedure to iteratively select the most influential network parameters, and it uses a swarm intelligence procedure to perform parameter optimization. We have conducted a series of experiments to evaluate the external behaviors and internal robustness of the networks inferred by the proposed approach. The results and analyses have verified the effectiveness of our approach.ConclusionsSensitivity analysis is crucial to identifying the most sensitive parameters that govern the network dynamics. It can further be used to derive constraints for network parameters in the network reconstruction process. The experimental results show that the proposed approach can successfully infer robust GRNs with desired system behaviors.

Topology Optimization for Static Shape Control of Piezoelectric Plates With Penalization on Intermediate Actuation Voltage

This paper investigates the simultaneous optimal distribution of structural material and trilevel actuation voltage for static shape control applications. In this optimal design problem, the shape error between the actuated and the desired shapes is chosen as the objective function. The energy and the material volume are taken as constraints in the optimization problem formulation. The discrete-valued optimization problem is relaxed using element-wise continuous design variables representing the relative material density and the actuation voltage level. Artificial interpolation models which relate the mechanical/piezoelectrical properties of the material and the actuation voltage to the design variables are employed. Therein, power-law penalization functions are used to suppress intermediate values of both the material densities and the control voltage. The sensitivity analysis procedure is discussed, and the design variables are optimized by using the method of moving asymptotes (MMA). Finally, numerical examples are presented to demonstrate the applicability and effectiveness of the proposed method. It is shown that the proposed method is able to yield distinct material distribution and to suppress intermediate actuation voltage values as required.

A fully multiple‐criteria implementation of the Sobol′ method for parameter sensitivity analysis

We present a novel rank‐based fully multiple‐criteria implementation of the Sobol′ variance‐based sensitivity analysis approach that implements an objective strategy to evaluate parameter sensitivity when model evaluation involves several metrics of performance. The method is superior to single‐criterion approaches while avoiding the subjectivity observed in “pseudo” multiple‐criteria methods. Further, it contributes to our understanding of structural characteristics of a model and simplifies parameter estimation by identifying insensitive parameters that can be fixed to default values during model calibration studies. We illustrate the approach by applying it to the problem of identifying the most influential parameters in the Simple Biosphere 3 (SiB3) model using a network of flux towers in Brazil. We find 27–31 (out of 42) parameters to be influential, most (∼78%) of which are primarily associated with physiology, soil, and carbon properties, and that uncertainties in the physiological properties of the model contribute most to total model uncertainty in regard to energy and carbon fluxes. We also find that the second most important model component contributing to the total output uncertainty varies according to the flux analyzed; whereas morphological properties play an important role in sensible heat flux, soil properties are important for latent heat flux, and carbon properties (mainly associated with the soil respiration submodel) are important for carbon flux (as expected). These distinct sensitivities emphasize the need to account for the multioutput nature of land surface models during sensitivity analysis and parameter estimation. Applied to other similar models, our approach can help to establish which soil‐plant‐atmosphere processes matter most in land surface models of Amazonia and thereby aid in the design of field campaigns to characterize and measure the associated parameters. The approach can also be used with other sensitivity analysis procedures that compute at least two model performance metrics.

Validated spectrophotometric methods for determination of Alendronate sodium in tablets through nucleophilic aromatic substitution reactions

BackgroundAlendronate (ALD) is a member of the bisphosphonate family which is used for the treatment of osteoporosis, bone metastasis, Paget's disease, hypocalcaemia associated with malignancy and other conditions that feature bone fragility. ALD is a non-chromophoric compound so its determination by conventional spectrophotometric methods is not possible. So two derivatization reactions were proposed for determination of ALD through the reaction with 4-chloro-7-nitrobenzo-2-oxa-1,3-diazole (NBD-Cl) and 2,4-dinitrofluorobenzene (DNFB) as chromogenic derivatizing reagents.ResultsThree simple and sensitive spectrophotometric methods are described for the determination of ALD. Method I is based on the reaction of ALD with NBD-Cl. Method II involved heat-catalyzed derivatization of ALD with DNFB, while, Method III is based on micellar-catalyzed reaction of the studied drug with DNFB at room temperature. The reactions products were measured at 472, 378 and 374 nm, for methods I, II and III, respectively. Beer's law was obeyed over the concentration ranges of 1.0-20.0, 4.0-40.0 and 1.5-30.0 μg/mL with lower limits of detection of 0.09, 1.06 and 0.06 μg/mL for Methods I, II and III, respectively. The proposed methods were applied for quantitation of the studied drug in its pure form with mean percentage recoveries of 100.47 ± 1.12, 100.17 ± 1.21 and 99.23 ± 1.26 for Methods I, II and III, respectively. Moreover the proposed methods were successfully applied for determination of ALD in different tablets. Proposals of the reactions pathways have been postulated.ConclusionThe proposed spectrophotometric methods provided sensitive, specific and inexpensive analytical procedures for determination of the non-chromophoric drug alendronate either per se or in its tablet dosage forms without interference from common excipients.Graphical abstract

Process enhancement through waste minimization and multiobjective optimization

Abstract A simultaneous approach to maximize profit, while minimizing waste through source reduction with the implementation of multiobjective optimization with process simulation is presented in this paper. To demonstrate this methodology, the acrylonitrile process case study was selected. The approach involved four steps: process modeling and analysis, identification of process alternatives, selection of process alternatives and incorporation of multiobjective optimization. The simulator ASPEN PLUS™ 12.1 was used to model and evaluate the process. Process alternatives were identified from both literature and sensitivity analysis procedures. Sensitivity analysis helps initially in quickly eliminating inferior alternatives and then in enhancing the superior alternative to develop an efficient optimization procedure. Through this work, a general methodology was developed for the application of process optimization to process design. A sensitivity curve that shows the effect of waste treatment on the profit for the process was developed. Based on the sensitivity analysis results, the Plug Flow reactor scheme was the better alternative as compared to the base case, CSTR reactor scheme. After process modification and optimization, the process can earn a maximum net savings of $ 3.59 × 108 in seven years, an increase of 69% over the base case. At the other end of the spectrum, the modified process could generate waste of 1884 kg h−1, a 38% reduction compared to the base case. The modified optimized process is observed to show significant improvements in environmental impacts as analyzed by the Waste Reduction Algorithm.