Total Analyte Concentration Research Articles

Optical Relay Sensing of Cryptochiral Alcohols Displaying α-, β-, γ- and δ-Stereocenters or Chirality by Virtue of Isotopic Substitution.

A reaction-based optical relay sensing strategy that enables accurate determination of the concentration and enantiomeric ratio (er) of challenging chiral alcohols exhibiting stereocenters at the α-, β-, γ- or even δ-position or hard-to-detect cryptochirality arising from H/D substitution is described. This unmatched application scope is achieved with a conceptually new sensing approach by which the alcohol moiety is replaced with an optimized achiral sulfonamide chromophore to minimize the distance between the covalently attached chiroptical reporter unit and the stereogenic center in the substrate. The result is a remarkably strong, red-shifted CD induction that increases linearly with the sample er. The CD sensing part of the tandem assay is seamlessly coupled to a redox reaction with a quinone molecule to generate a characteristic UV response that is independent of the enantiopurity of the alcohol and thus allows determination of the total analyte concentration. The robustness and utility of the CD/UV relay are further verified by chromatography-free asymmetric reaction analysis with small aliquots of crude product mixtures, paving the way toward high-throughput chiral compound screening workflows which is a highly sought-after goal in the pharmaceutical industry.

Optical Relay Sensing of Cryptochiral Alcohols Displaying α‐, β‐, γ‐ and δ‐Stereocenters or Chirality by Virtue of Isotopic Substitution

AbstractA reaction‐based optical relay sensing strategy that enables accurate determination of the concentration and enantiomeric ratio (er) of challenging chiral alcohols exhibiting stereocenters at the α‐, β‐, γ‐ or even δ‐position or hard‐to‐detect cryptochirality arising from H/D substitution is described. This unmatched application scope is achieved with a conceptually new sensing approach by which the alcohol moiety is replaced with an optimized achiral sulfonamide chromophore to minimize the distance between the covalently attached chiroptical reporter unit and the stereogenic center in the substrate. The result is a remarkably strong, red‐shifted CD induction that increases linearly with the sample er. The CD sensing part of the tandem assay is seamlessly coupled to a redox reaction with a quinone molecule to generate a characteristic UV response that is independent of the enantiopurity of the alcohol and thus allows determination of the total analyte concentration. The robustness and utility of the CD/UV relay are further verified by chromatography‐free asymmetric reaction analysis with small aliquots of crude product mixtures, paving the way toward high‐throughput chiral compound screening workflows which is a highly sought‐after goal in the pharmaceutical industry.

(R)evolution of the Standard Addition Procedure for Immunoassays.

A new method to transfer the standard addition procedure for concentration determination to immunoassays with non-linear calibration curves was developed. The new method was successfully applied to simulated data and benchmarked against a state-of-the-art algorithm, showing a significantly improved performance with improvement factors between 2 and 192. The logit function was used to transform the immunoassay signal response of test samples spiked with known analyte concentrations. The relationship between logit(signal) and log-transformed estimated total analyte concentration is linear if the estimated total analyte concentration is correct. Finally, the new method was validated experimentally using different assays in varying, relevant complex matrices, such as serum, saliva, and milk. Different concentrations of testosterone and amitriptyline between 0.05 and 3.0 µg L-1 were quantified using a binding inhibition assay in combination with reflectometric interference spectroscopy (RIfS) as the transduction principle. The sample concentration was calculated using a numerical method. Samples could be quantified with recoveries between 70 and 118%. The standard addition method accounts for individual matrix interference on the immunoassay by spiking the test sample itself. Although the experiments were carried out using RIfS, the method can be applied to any immunoassay that meets the analytical requirements.

Possibilities and Limitations of ICP-Spectrometric Determination of the Total Content of Tin, Its Inorganic and Organic Speciations in Waters with Different Salinity Levels-Part 1: Determination of the Total Tin Content.

This paper considers the features of determining the total tin content in waters with different salinity. Direct ICP-spectrometric analysis of sea waters with a salinity of more than 6‱ significantly reduced the analytical signal of tin by 70% (ICP-MS) and 30% (ICP-OES). The matrix effect of macrocomponents was eliminated by generating hydrides using 0.50 M sodium borohydride and 0.10 M hydrochloric acid. The effect of transition metals on the formation of tin hydrides was eliminated by applying L-cysteine at a concentration of 0.75 g/L. The total analyte concentrations, considering the content of organotin compounds, were determined after microwave digestion of sample with oxidizing mixtures based on nitric acid. The generation of hydrides with the ICP-spectrometric determination of tin leveled the influence of the sea water matrix and reduced its detection limit from 0.50 up to 0.05 µg/L for all digestion schemes. The developed analysis scheme made it possible to determine the total content of inorganic and organic forms of tin in sea waters. The total content of tin was determined in the waters of the Azov and Black seas at the levels of 0.17 and 0.24 µg/L, respectively.

Abemaciclib does not increase the corrected QT interval in healthy participants.

Abemaciclib is an orally administered potent and selective small molecule inhibitor of cyclin dependent kinases 4 and 6, approved for advanced or metastatic breast cancer. This study aimed to use an exposure-response approach to investigate the effect of abemaciclib and its active metabolites (M2 and M20) on QTc interval and delay in cardiac repolarization at clinically relevant exposures. This was a single-blind, randomized and placebo-controlled study of ascending doses of abemaciclib. Thirty-five healthy participants were administered a single dose of 200 to 600 mg abemaciclib. Twelve-lead electrocardiogram tracings and pharmacokinetic samples were collected serially pre- and post-dose. The primary objective was to study the relationship between abemaciclib and its active metabolites (M2 and M20) and QTc interval following ascending oral doses of abemaciclib. The secondary objective included evaluating the safety and tolerability of single ascending doses of abemaciclib in healthy participants. Exposure-response analysis demonstrated that there was no significant relationship between placebo-corrected change from baseline QTcF (ΔΔQTcF), abemaciclib and metabolite plasma concentrations. Additionally, the ΔΔQTcF slopes of abemaciclib, its metabolites, and total analyte concentrations were not statistically different from zero. Single doses of abemaciclib, up to 400 mg, were well-tolerated by healthy participants; however, at the 600 mg dose (3-times highest registered dose), the frequency and severity of treatment-related gastrointestinal events (primarily diarrhea, nausea, and vomiting) increased. In conclusion, single doses of abemaciclib, up to 400 mg, had no statistically or clinically relevant effects on QTc, and abemaciclib was well-tolerated up to a dose of 400 mg in this study. This article is protected by copyright. All rights reserved.

Spectrometric Determination of the Total Concentration of Similar Analytes Using Inverted Multivariate Calibrations

Spectrometric Determination of the Total Concentration of Similar Analytes Using Inverted Multivariate Calibrations

Multi-temperature experiments to ease analysis of heterogeneous binder solutions by surface plasmon resonance biosensing

Surface Plasmon Resonance (SPR) biosensing is a well-established tool for the investigation of binding kinetics between a soluble species and an immobilized (bio)molecule. While robust and accurate data analysis techniques are readily available for single species, methods to exploit data collected with a solution containing multiple interactants are scarce. In a previous study, our group proposed two data analysis algorithms for (1) the precise and reliable identification of the kinetic parameters of N interactants present at different ratios in N mixtures and (2) the estimation of the composition of a given mixture, assuming that the kinetic parameters and the total concentration of all interactants are known. Here, we extend the first algorithm by reducing the number of necessary mixtures. This is achieved by conducting experiments at different temperatures. Through the Van’t Hoff and Eyring equations, identifying the kinetic and thermodynamic parameters of N binders becomes possible with M mixtures with M comprised between 2 and N and at least N/M temperatures. The second algorithm is improved by adding the total analyte concentration as a supplementary variable to be identified in an optimization routine. We validated our analysis framework experimentally with a system consisting of mixtures of low molecular weight drugs, each competing to bind to an immobilized protein. We believe that the analysis of mixtures and composition estimation could pave the way for SPR biosensing to become a bioprocess monitoring tool, on top of expanding its already substantial role in drug discovery and development.

Erratum to: Spectrometric Determination of the Total Concentration of Single-Type Analytes Using Conventional Multidimensional Calibrations

Erratum to: Spectrometric Determination of the Total Concentration of Single-Type Analytes Using Conventional Multidimensional Calibrations

Tobacco-specific and combustion pollutants in settled house dust in Malta.

Aim:Most of the carcinogenic pollutants coming from tobacco smoking or other combustion processes tend to accumulate in settled house dust (SHD) over time. This study evaluated the load of these pollutants in smokers and non-smokers’ houses from relatively fresh SHD collected in five different districts on the island of Malta.Methods:An improved, efficient extraction method to obtain three fractions from a 200 mg of SHD was developed. It was validated for the analysis of nicotine and polycyclic aromatic hydrocarbons (PAH) by GC-MS/MS and nicotelline and TSNA by LC-MS/MS. Kruskal-Wallis H tests were used to evaluate differences across districts, while a Mann-Whitney U test was used to check differences between smokers and non-smokers’ houses. Diagnostic ratios were used to evaluate the carcinogenicity of PAH in SHD in Malta.Results:For all analytes, no statistical difference was observed across different districts, but, in smokers’ houses, 97.9% of the total concentration of all target analytes found in SHD is nicotine, 0.1% is TSNA, and 2.0% is PAH. In non-smokers’ houses, nicotine represents 16.8% of the load, while 0.4% and 82.8% are TSNA and PAH, respectively. The carcinogenicity of the PAH mixture in Maltese SHD, expressed as the mean benzo(a)pyrene equivalent (BaPeq) is 371 ng/g.Conclusion:Indoor activities, ventilation practices, and infiltration of outdoor pollutants contribute to a complex SHD composition. Although the BaPeq is on the lower end of carcinogenicity, the effects of a mixture including tobacco-related potent carcinogens in SHD are largely unknown. In view of indoor, continuous exposure to SHD through several pathways, further research is warranted.

Radial basis function-artificial neural network (RBF-ANN) for simultaneous fluorescent determination of cysteine enantiomers in mixtures

The determination of chiral compounds is critically important in chemical and pharmaceutical sciences. Cysteine amino acid is one of the important chiral compounds where each enantiomer (L and D) has different effects on fundamental physiological processes. The unique optical properties of nanoparticles make them a suitable probe for the determination of different analytes. In this work, the water-soluble thioglycolic acid (TGA)-capped cadmium-telluride (CdTe) quantum dots (QDs) were applied as optical nanoprobe for the simultaneous determination of cysteine enantiomers. The difference in the kinetics of the interactions between L- and D-cysteine with CdTe QDs is used for multivariate quantitative analysis. Multivariate methods are superior to univariate methods in determining the concentration of each enantiomer in the mixture without the information about the total chiral analyte concentration. As a nonlinear calibration method the radial basis function -artificial neural network (RBF-ANN) model was more successful in predicting L-and D-cysteine concentrations than the linear partial least squares regression (PLS) model.

Assessment of bisphenol A alternatives in paper products from the Chinese market and their dermal exposure in the general population

Bisphenol A (BPA), a well-known endocrine disruptor, is used as a color developer in thermal paper. More recently, some emerging structural analogues have been introduced to replace BPA due to the strengthened regulations concerning thermal paper. Nevertheless, very limited data are available regarding their occurrence and potential health risks. Here, thirteen potentially toxic compounds were investigated in paper products (120 thermal papers and 81 nonthermal papers) collected in Beijing, China. The results indicated that the replacement of BPA by alternatives such as Bisphenol S (BPS), Bis(2-chloroethyl)ether-4,4″-dihydroxydiphenyl sulfone copolymer (D-90), 4-hydroxyphenyl 4-isoprooxyphenylsulfone (D-8), Bis(4-hydroxyphenyl)sulfonylphenyl (BPS-MAE) and Bis-(3-allyl-4-hydroxyphenyl) sulfone (TGSA) has been significantly advanced in several types of thermal paper (i.e., market weight stickers, train tickets, express labels, air boarding passes and lottery tickets). The mean value for the total analyte concentrations in thermal paper was 6.06 mg/g, and the highest level found was 26.0 mg/g. In addition, the frequent detection of these chemicals in nonthermal paper (>80%, n = 81) demonstrated that the contamination in thermal paper can be spread into other recycled paper, such as corrugated boxes, newspapers, food contact papers, etc. The estimated daily intake of BPA and its alternatives through the handling of thermal paper was 0.025 μg/kg bw/day for the general population. This is the first report on the occurrence of various new BPA alternatives in paper products from China, which will be helpful for further risk assessment and making responsible replacement decisions.

A Rapid Method, Combining Microwave-Assisted Extraction and Gas Chromatography-Mass Spectrometry with a Database, for Determining Organochlorine Pesticides and Polycyclic Aromatic Hydrocarbons in Soils and Sediments

ABSTRACTA rapid method for determining organochlorine pesticides and polycyclic aromatic hydrocarbons in soils and sediments was developed to allow pollution surveys to be performed in emergencies. The method involves microwave-assisted extraction and uses an automated identification/quantification system with a gas chromatography mass spectrometry database. A sample (3 g) is extracted with a 3:2 v/v hexane:water mixture (10 mL) for 30 min using a microwave-assisted extraction system at 120°C. The hexane extract is then cleaned using silica gel, then analyzed by gas chromatography mass spectrometry. The total analysis time is approximately 4 h. The precision of the quantitative results and accuracy of the analyte identification were determined. The total analyte concentrations were generally comparable to (61%–110% of) the concentrations determined using a Soxhlet extraction method, but the concentrations of individual high-molecular-weight polycyclic aromatic hydrocarbons were unacceptably low compared with the concentrations determined using the Soxhlet method. However, these compounds (e.g., benzo(ghi)perylene and indeno(1,2,3-cd)pyrene) were subsequently efficiently extracted using a hexane:water:ethanol mixture. The accuracy of identification was evaluated using accurate masses determined by gas chromatography time-of-flight mass spectrometry, and the mass error was 2 ppm for 21 of the 22 compounds identified using the new method.

A generic standard additions based method to determine endogenous analyte concentrations by immunoassays to overcome complex biological matrix interference

We describe a novel generic method to derive the unknown endogenous concentrations of analyte within complex biological matrices (e.g. serum or plasma) based upon the relationship between the immunoassay signal response of a biological test sample spiked with known analyte concentrations and the log transformed estimated total concentration. If the estimated total analyte concentration is correct, a portion of the sigmoid on a log-log plot is very close to linear, allowing the unknown endogenous concentration to be estimated using a numerical method. This approach obviates conventional relative quantification using an internal standard curve and need for calibrant diluent, and takes into account the individual matrix interference on the immunoassay by spiking the test sample itself. This technique is based on standard additions for chemical analytes. Unknown endogenous analyte concentrations within even 2-fold diluted human plasma may be determined reliably using as few as four reaction wells.

Biomimetic Chirality Sensing with Pyridoxal-5'-phosphate.

Pyridoxal-5'-phosphate (PLP) is introduced to a biomimetic indicator displacement assay for simultaneous determination of the absolute configuration, enantiomeric composition and concentration of unprotected amino acids, amino alcohols and amines. The chiroptical assay is based on fast imine metathesis with a PLP aryl imine probe to capture the target compound for circular dichroism and fluorescence sensing analysis. The substrate binding yields characteristic Cotton effects that provide information about the target compound ee and the synchronous release of the indicator results in a nonenantioselective off-on fluorescence response that is independent of the enantiomeric sample composition and readily correlated to the total analyte concentration.

Methodology of analysis of unseparated mixtures: Interval estimates of the total concentration of similar analytes

Determination of the total concentration (c Σ) of similar analytes recalculated to a standard substance Xst is a widely used but metrologically incorrect procedure leading to a high uncertainty of the results of analysis. An algorithm is proposed for the interval estimation of c Σ without recalculating to the concentration of Xst. The algorithm takes into account different sensitivities of the determination of analytes of the studied type. No information on the nature and ratio of analytes in the sample is used. The width of the range of possible values of c Σ objectively characterizes the systematic component of the error, it is independent of the choice of Xst, exceeds the width of traditional confidence intervals, and becomes zero at equal sensitivities of the determination of all analytes in a group. The accuracy of interval estimates is supported by the analysis of model mixtures of different types using several methods of measuring the total signal.

Estimation of the bio-accessible fraction of Cr, As, Cd and Pb in locally available bread using on-line continuous leaching method coupled to inductively coupled plasma mass spectrometry

A previously developed, efficient and simple on-line leaching method was used to assess the maximum bio-accessible fraction (assuming no synergistic effect from other food and beverage) of potentially toxic elements (Cr, As, Cd and Pb) in whole wheat brown and white bread samples. Artificial saliva, gastric juice and intestinal juice were successively pumped into a mini-column, packed with bread (maintained at 37°C) connected on-line to the nebulizer of an inductively coupled plasma mass spectrometry (ICP-MS) instrument equipped with a collision-reaction interface (CRI) using hydrogen as reaction gas to minimize carbon- and chlorine-based polyatomic interferences. In contrast to the conventional batch method to which it was compared, this approach provides real-time monitoring of potentially toxic elements that are continuously released during leaching. Mass balance for both methods was verified at the 95% confidence level. Results obtained from the whole wheat brown and white bread showed that the majority of Cr, Cd and Pb was leached by gastric juice but, in contrast, the majority of As was leached by saliva. While there was higher total content for elements in whole wheat bread than in white bread, a higher percentage of elements were bio-accessible in white bread than in whole wheat bread. Both the on-line and batch methods indicate that 40–98% of toxic elements in bread samples are bio-accessible. While comparison of total analyte concentrations with provisional tolerable daily intake values may indicate some serious health concern for children, when accounting for the bio-accessibility of these elements, bread consumption is found to be safe for all ages.

Determination of Surfactants in Environmental Samples. Part II. Anionic Compounds

Abstract Surface active agents (SAA) with negative charge of polar group are named as anionic compounds. They are the main constituent of most products containing synthetic surfactants. The linear alkylbenzene sulfonates (LAS), alkyl ethoxysulfates (AES) and alkyl sulfates (AS) are typically applied from this class of compounds. Those surfactants are ingredients of household detergents and cleaners, laundry detergents, cosmetic etc. Moreover they can be applied in the paper, textile and tanning industry as optical brighteners, dispersant, wetting and suspending agents. They can be substrates in the formulation of different products like dyes, pigments, pesticides, exchange resins, plasticizers and pharmaceuticals. Anionic surfactants after use are passed into sewage-treatment plants, where they are partially degraded and adsorbed to sewage sludge (applied in agriculture fields). Finally, the anionic SAA or their degradation products are discharged into surface waters and onto bottom sediments, soils or living organisms. Therefore, it is important (widely application, bioaccumulation, toxicity for living organisms) to investigate the environmental fate of those class of compounds in more details. This research involves determination the concentration of anionic surfactants with use appropriated analytical techniques in environmental samples The official methodology for determination of anionic SAA in liquid samples is based on the ion-pair reaction of these analytes compounds with methylene blue (MB) and an extraction with toxic solvent chloroform. During isolation step of anionic compounds from solid samples are employed Soxhlet and ultrasonic-assisted extraction techniques with use of methanol or mixture of other organic solvents as extraction medium. To overcome disadvantages of those traditional techniques were applied following techniques at sample preparation step from liquid and solid matrices: solid-phase extraction (SPE) and solid-phases microextraction (SPME); accelerated solvent extraction (ASE), microwave-assisted extraction (MAE), supercritical fluid extraction (SFE), respectively. For estimate total concentration of anionic analytes in extracts the spectrophotometric technique is used (as official regulation). For determination concentration of individual analytes were applied gas (derivatization step requires) and liquid chromatography mainly with mass spectrometry technique. The presence of anionic surface active agents was confirmed in various ecosystems (liquid and solid environmental samples).

Methodology of analysis of unseparated mixtures: Error limits in estimating the total analyte concentration recalculated to a standard substance

In estimating the total concentration of similar analytes recalculated to a standard substance Xst, different sensitivities of their determination result in a systematic error δc, depending on the choice of Xst and the composition of the analyzed mixture. Two methods of predicting the limiting values of this error (δc max), with and without the account of the properties of Xst are proposed and tested on model mixtures. The methods can be used if the total analytical signal linearly depends on the concentrations of analytes and is additive (spectrophotometry, conductometry, etc.). The value of δc max is independent of the ratio of analytes concentrations in the sample. To reduce δc max, one should equalize the sensitivities of the determination of all compounds of a given type and use analytes with medium sensitivities as Xst.

Sucrose as chiral selector for determining enantiomeric composition of metalaxyl by UV–vis spectroscopy and PLS regression

This study revealed that it was possible to determine the enantiomeric composition of with multivariate regression models of spectral data obtained by ordinary UV–vis spectrophotometry of enantiomeric guest–host complexes. The total 60samples involving three concentration levels of metalaxyl as low, medium and high were prepared for spectral collecting. Four methods of modeling were subsequently proposed and compared including two common ways and two compensating ways for variations in total analyte concentration. Firstly, without normalization robust modeling was failed to achieve while employing the medium concentration levels as calibration and the other two levels as a validation. The same case occurred when full-cross validation was conducted. Besides, two enhanced methods were developed to account for the systematic variation. One of which normalized the spectra with respect to the total concentration of enantiomeric, along with spectral data, as a variable in the statistical analysis. The other one ignored variations in total concentration, relying on the specific band normalization to sort out any variations due to total concentration differences. The results clearly demonstrated that the spectra according to concentration provided the acceptable predictive ability in determining enantiomeric composition.

Methodology of the spectrophotometric analysis of organic mixtures: Error of estimating total analyte concentrations taking into account their sensitivity coefficients

In estimating the total concentration of similar analytes in recalculated to the reference substance of Xst, different sensitivities of the photometric determinations of analytes and Xst result in systematic errors depending on the choice of Xst and sample composition. A method of prediction of this error is proposed and tested on model antioxidant mixtures. Its application to the analysis of mixtures with approximately known compositions allows the optimization of the choice of Xst and can improve the accuracy of estimating the total concentration of analytes.