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The antioxidant properties of plants have been investigated, in the light of recent scientific developments, throughout the world due to their potent pharmacological activities and food viability. Basil (Ocimum basilicum L. Family Lamiaceae) is used as a kitchen herb and as an ornamental plant in house gardens. In the present study, the possible radical scavenging and antioxidant activity of the water (WEB) and ethanol extracts (EEB) of basil was investigated using different antioxidant methodologies: 1,1-diphenyl-2-picryl-hydrazyl (DPPH) free radical scavenging, scavenging of superoxide anion radical-generated non-enzymatic system, ferric thiocyanate method, reducing power, hydrogen peroxide scavenging and metal chelating activities. Experiments revealed that WEB and EEB have an antioxidant effects which are concentration-dependent. The total antioxidant activity was performed according to the ferric thiocyanate method. At the 50 microg/mL concentration, the inhibition effects of WEB and EEB on peroxidation of linoleic acid emulsion were found to be 94.8% and 97.5%, respectively. On the other hand, the percentage inhibition of a 50 microg/mL concentration of BHA, BHT and alpha-tocopherol was found to be 97.1%, 98.5% and 70.4% inhibition of peroxidation of linoleic acid emulsion, respectively. In addition, WEB and EEB had effective DPPH radical scavenging, superoxide anion radical scavenging, hydrogen peroxide scavenging, reducing power and metal chelating activities. Additionally, these various antioxidant activities were compared with BHA, BHT and alpha-tocopherol as reference antioxidants. The additional total phenolic content of these basil extracts was determined as the gallic acid equivalent and were found to be equivalent. [ABSTRACT FROM AUTHOR]

The coupling of capillary electrophoresis (CE) with capacitively coupled contactless conductivity detection (C 4 D) has become convenient analytical method for determination of small molecules that do not possess chromogenic or fluorogenic group. The implementations of CE with C 4 D in the determination of inorganic and organic ions and amino acids in biomedical field are demonstrated. Attention on background electrolyte composition, sample treatment procedures, and the utilize of multi-detection systems are described. A number of tables summarizing highly developed CE-C 4 D methods and the figures of merit attained are involved. Lastly, concluding remarks and perspectives are argued., (© 2023 Wiley-VCH GmbH.)

Chiral high performance liquid chromatographic technique usually employs polysaccharide-based stationary phases in a normal phase mode. This frequently generates large waste of organic solvents. Using shorter columns of 50 mm length as well as a mobile phase with a high water percentage are common approaches for greening this analytical technique. In this context, a new chiral chromatographic technique was developed for simultaneous enantio-separation of phenylephrine HCl and guaifenesin racemates. Four 50 mm cellulose-based columns were experimented to separate the four enantiomers in a reversed phase mode. A face centered design was then employed to optimize the mobile phase acetonitrile% and flow rate on Lux Cellulose-1 (50 × 4.6 mm, 5 μm). The simultaneous resolution of the cited drugs enantiomers was achieved using acetonitrile-water (30:70, by volume), with a flow rate of 0.5 ml min -1 . These optimized chromatographic conditions separate the enantiomers in 7 min running time, generating about 1.0 ml acetonitrile per run. The proposed method was favorably compared with other reported chiral ones in terms of waste volume generated and analysis time required., (© 2023 Wiley Periodicals LLC.)

The study of antibody-antigen interactions, through epitope mapping, enhances our understanding of antibody neutralization and antigenic determinant recognition. Epitope mapping, employing monoclonal antibodies and mass spectrometry, has emerged as a rapid and precise method to investigate viral antigenic determinants. In this report, we propose an approach to improve the accuracy of epitopic peptide interaction rate recognition. To achieve this, we investigated the interaction between the nucleocapsid protein of fig mosaic virus (FMV-NP) and single-chain variable fragment antibodies (scFv-Ab). These scFv-Ab maintain high specificity similar to whole monoclonal antibodies, but they are smaller in size. We coupled this with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). The experimental design involved using two different enzymes to digest FMV-NP separately. The resulting peptides were then incubated separately with the desired scFv-Ab at different incubation times and antibody concentrations. This allowed us to monitor the relative rate of epitopic peptide interaction with the antibody. The results demonstrated that, at a 1:1 ratio and after 2 h of interaction, the residues 122-136, 148-157, and 265-276 exhibited high-rate epitopic peptide binding, with reductions in peak intensity of 78%, 21%, and 22%, respectively. Conversely, the residues 250-264 showed low-rate binding, with a 15% reduction in peak intensity. This epitope mapping approach, utilizing scFv-Ab, two different enzymes, and various incubation times, offers a precise and dependable analysis for monitoring and recognizing the binding kinetics of antigenic determinants. Furthermore, this method can be applied to study any kind of antigens., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Inc.)

Coffee is a complex mixture of chemicals, which provide biologically active compounds with various health benefits. The some biologically active compounds arising from both its natural structure and formed after processing were determined as an antioxidant capacity of coffee beverages. In this study, we aimed to determine how roasting levels of Arabica coffee seed (light, medium, dark) and three brewing techniques-decoction methods (Turkish coffee), infusion method (filter coffee) and pressure methods (Espresso)-affect total antioxidant capacity in a cup of coffee beverage by electrochemical methods such as square wave stripping voltammetry (SWSV), differential pulse stripping voltammetry (DPSV) and cyclic voltammetry (CV). Antioxidant capacities of the coffee samples in terms of the equivalent amounts were determined according to standard oxidation peaks of rutin and caffeic acid. The highest antioxidant capacity was found in espresso coffee prepared at light roasting coffee seeds as equivalent the routine and caffeic at 9.4 ± 0.2 g/L and 19.7 ± 0.7 g/L, respectively with SWSV on a carbon paste electrode. As a result, SWSV, DPSV and CV voltammetric methods, fast, reliable, fully validated and without any pretreatment are alternative to conventional analytical methods to evaluation antioxidant values in any food samples., Competing Interests: Conflict of interestThe authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. The authors declare no conflict of interest., (© Association of Food Scientists & Technologists (India) 2022.)

Enantioseparation of five β-adrenergic blockers was studied using two mobile phases on a cellulose tris(3-chloro-4-methylphenylcarbamate) (Lux-Cellulose-2) chiral column in normal phase mode. The first mobile phase composed of n-hexane: ethanol: diethylamine 60: 40: 0.1 by volume has successfully resolved the chromatographic peaks of three pairs of β-adrenergic blockers namely, bisoprolol, carvedilol and atenolol. A mixture of n-hexane: ethanol: diethyl amine 75: 25: 0.1 by volume was used as the second mobile phase to separate the four pairs of enantiomers, metoprolol, carvedilol, nebivolol and atenolol with high resolution values. The mobile phases were pumped at a flow rate 1 mL/min with column temperature 25 °C using a UV detector at 230 nm. Molecular docking simulations of the five pairs of enantiomers was carried out in the cavities of the chiral stationary phase to gain a better understanding of the interaction between analyte enantiomers and chiral stationary phase and to better understand the mechanism of chiral recognition. According to the results, hydrogen bond interactions and π-π- interactions were the main types of interaction involved in the chiral recognition. Molecular dynamics simulation was performed to investigate the solvent effect on the interaction of the five pair of enantiomers in the chiral stationary phase cavity under dynamic conditions., (© 2023. The Author(s).)

The recent development of monolithic chiral stationary phases (CSPs) for liquid chromatography (LC) is mainly focused on reducing backpressure, maximizing flow rates, faster run time, column efficiency, and stability. This review paper emphasizes recent progress in the development of polysaccharide and cyclodextrin-based monolithic CSPs. Further the paper draws attention to competing techniques, like non-porous particle-packed columns, core-shell and monoliths as chromatographic support matrix, available for achieving fast and efficient chromatographic separation. A brief discussion on the three main classes of chiral monolithic stationary phase viz. silica, organic polymer and hybrid-based monolithic stationary phases is also presented. In addition, the paper highlights various studies on the application of monolith chiral CSPs in LC and capillary electrochromrography separation and analysis of chiral compounds., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

2-Arylpropionic acid nonsteroidal anti-inflammatory drugs (NSAIDs) provide one of the most demonstrated pharmaceutical examples of chiral inversion. Chiral inversion depends on various factors ( viz . biological-, solvent-, light-, temperature-induced, etc .) and the energy barrier associated with the stereogenic element present in the chiral molecule. The pharmacological properties of chiral drugs depend on the activity of one enantiomer or both the enantiomers targeting different biological targets. Consequently, chiral inversion can alter the biological activities of the pharmaceutical drug. Hence a better understanding of chiral inversion, factors facilitating such inversion, and the tools employed to determine chiral inversion are of great significance from a pharmacological and toxicological perspective., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Despite organophosphorus pesticides (OPPs) benefits in controlling vector-borne diseases and noxious insects, the bioaccumulation and persistence in the soil system may metamorphose into new substances which could pose a serious threat to the ecosystems and human health. The generally low levels of OPPs residues and often the complexity of the soil matrix are the issues that researcher must deal with. Thus, it is essential to isolate and preconcentrate the OPPs from the matrix to reduce interference effects to obtain a reliable detection. Researchers have reported sample preparation techniques as a promising approach to improve analytical measurement of merits including recovery, precision, linearity, limit of detection, and limit of quantification. Under the selected conditions, limits of detection range between 0.001 and 143 ng/mL, and extraction recovery range between 5 and 154% were obtained. This review evaluates the challenges and opportunities, emphasizes the prospects of sampling techniques and various (micro)extraction coupled with chromatographic methods in different soil samples. Based on the finding, the extraction efficiency depended largely on the interaction between OPPs and extraction media. The fate, migration, toxicity impact, sampling procedure, and storage which influenced the sample preparation were comprehensively discussed.

A multimode sensor (a sensor responding simultaneously to more than one mode, e.g., stochastic mode, amperometric mode, voltammetric mode) based on graphite paste modified with N -methylfulleropyrrolidine was proposed for the determination of butoconazole nitrate in its pharmaceutical formulation. The stochastic mode and square wave voltammetry mode were applied for the determinations. Both the stochastic mode and square wave voltammetry mode were applied for a qualitative and quantitative assay of butoconazole nitrate. The sensor can be used between 1.68 × 10 -6 and 1.68 × 10 4 μmol L -1 when the stochastic mode is used and between 0.168 and 16.80 μmol L -1 when the square wave voltammetry mode is used. The multimode sensor was reliably used for the determination of butoconazole nitrate in its pharmaceutical formulation, Gynofort cream, the recorded recoveries being higher than 99.00%, with RSD (%) values of lower than 2.00%., Competing Interests: The authors declare no competing financial interest., (© 2022 The Authors. Published by American Chemical Society.)

Three chiral pyrazoline derivatives were synthesized by a flavanone ring-opening reaction followed by cyclocondensation with hydrazine hydrate to give better yields. Their enantiomeric resolution was achieved using polysaccharide chiral stationary phase columns consisting of cellulose (Chiralcel®OD-RH, Chiralcel®OZ-3) and amylose (Chiralpak®IA) by high-performance liquid chromatography. The separation was affected by the nature and concentration of the alcohol modifiers in the mobile phase. Taking 5-methoxy-2-(3-phenyl-4,5-dihydro-1H-pyrazol-5-yl)phenol (3a) as an example, the best separation was obtained by using the Chiralpak®IA column, with a separation factor α = 1.24 and Rs = 5.66 within an analysis time of <30 min. The diarylpyrazolines showed good antioxidant activity, studied by the DPPH method., (© 2022 Wiley Periodicals LLC.)

Arginine has an important role in the metabolomics of gastric cancer. Two 3D enantioselective needle stochastic sensors based on the physical immobilization of 2,3,7,8,12,13,17,18-octaethyl-21H,23H-porphine manganese(III) chloride (solution, 10 -3 mol L -1 ) in graphene paste matrices decorated with N and S atoms were designed, characterized and validated for the enantioanalysis of arginine in whole blood and tissue samples. The signature values obtained for the enantiomers of arginine confirmed that the stochastic sensors are enantioselective. The lowest limit of quantification obtained for both enantiomers of arginine was 1 fmol L -1 , while sensitivity of up to 10 11 s -1 mol -1 L was recorded for the stochastic sensors. High recoveries were obtained for the determination of one enantiomer in the presence of the other one; moreover, very good correlation was found between the results obtained with the two 3D enantioselective needle stochastic sensors., (© 2022. Springer-Verlag GmbH Germany, part of Springer Nature.)

Glutathione S-transferase P1 (GST-P1) is considered as a detoxification enzyme and can be upregulated in several cancers. Therefore, qualification and/or quantification of GST-P1 in biological fluids can be noteworthy in cancer diagnostic and/or prognostic methods. Whereas costly immunoassays methods are routinely used for clinical analysis, long analysis time per sample is still considered as their disadvantages. To create a fast, efficient, and economical GST-P1 qualification and/or quantification technique, we developed an affinity magnetic nanoparticle-MS method. In proposed method there is no need for any pretreatment for reducing the complexity of sample and depletion of high abundant proteins that are used in routinely immunoassays methods. After enrichment of GST-P1 from blood plasma samples by affinity magnetic nanoparticle (without any pretreatment), the final eluent was analyzed using MALDI-TOF, IM-Q-TOF and LC-ESI-Q-TOF MS. For the first time this study demonstrates the suitability of affinity magnetic nanoparticle-MS method for qualification/quantification of GST-P1 from acute lymphoblastic leukemia blood plasma samples with the limit-of-detection 0.0094 ppm in less than 5 h. Our finding showed that in these blood plasma samples the level of GST-P1 can be up to six times more than healthy children., (Copyright © 2021 Elsevier B.V. All rights reserved.)

The development of chiral selectors for the separation and analysis of chiral molecules has been an evolving process happening over three decades, since the introduction of the first chiral stationary phase (CSP) in 1938. The main impetus for designing new chiral selectors is to get to most promising one which has a broad chiral recognition property, separation capability for a wide range of chiral analytes, and the cost-effective CSP, which is also a major concern. Today, we have more than 100 commercially available CSPs, and these are prepared by coating or immobilizing the classical chiral selectors on to the chromatographic support, normally, silica gel. The purpose of this review is to look at progress and the impact of cyclofructan derivatives, a novel chiral selector introduced recently, for performing chiral analysis., (© 2021 Wiley Periodicals LLC.)

The sample preparation step is the initial step in pharmaceutical analysis. While ultrafiltration is a well-known technique used in the food and pharmaceutical industries, it has rarely been used to measure the plasma concentration of active pharmaceutical ingredients. This study aimed to analyze diclofenac sodium (DS) in human plasma samples using ultrafiltration-based sample preparation before high-performance liquid chromatography (HPLC) analysis. The advantages and limitations of ultrafiltration-based sample preparation in bioanalysis were evaluated by comparing the results with conventional methods. The precipitating agent was used before ultrafiltration. The analysis was carried on an HPLC-UV system with a C18 column (250 ×4.6 mm, 5 μm) and acetonitrile : phosphate buffer (pH 3.0, 10 mM) (70 : 30 v/v) was used as the mobile phase. The bioanalytical method was validated according to FDA guidelines and applied to spiked samples of DS in commercial human plasma samples. The LOD and LOQ values were 0.006 μg mL -1 and 0.020 μg mL -1 , respectively. The method was linear in the range of 0.025-0.50 μgmL -1 with excellent determination coefficients (R 2 > 0.9991). The findings of this analysis with low LOD and LOQ values and high recovery values with high trueness and precision proved the matrix minimizing the effect of the presented sample preparation technique., Competing Interests: Conflict of interest statement The authors declare there is no conflict of interest., (© TÜBİTAK.)

Capacitively coupled contactless conductivity detection (C 4 D) has emerged as influential to detect analytes that do not have chromogenic or fluorogenic functional group. Since our last review several new capillary electrophoresis (CE) methods coupled with (CE-C 4 D) have been communicated. The aim of this review is to give an update of the almost all the new applications of CE-C 4 D in the field of pharmaceutical, food and biomedical analysis covering the period from 2017 to April 2020. The utilization of CE with C 4 D in the areas of pharmaceutical, food and biomedical analysis is presented. Finally, concluding remarks and outlooks are discussed.

Recent success in studying the proteome, as a source of biomarkers, has completely changed our understanding of leukemia (blood cancer). The identification of differentially expressed proteins, such as relapse and drug resistance proteins involved in leukemia by using various ionization sources and mass analyzers of mass spectrometry techniques, has helped scientists find better diagnosis, prognosis, and treatment strategies. With the aid of this powerful analytical technique, we can investigate the qualification/quantification of proteins, protein-protein interactions, post-translational modifications, and find the correlation between proteins and their genes with the hope of finding the missing parts of the successful therapy puzzle. In this review, we followed different MS sources and analyzers which used for monitoring various type of leukemia, then focused on MALDI-TOF MS as a quick and reliable method for studying proteins. Due to several review published for other techniques, the present review is the first work in this field. Also, by classifying more than 400 proteins, we have found 42 proteins are involved in two or three different stages of leukemia. Finally, we have suggested six specific biomarkers for AML, one for ALL, three biomarkers with a role in the etiology of leukemia and 13 markers with the potential for further studies.

In this work, enantiomeric separation of a drug combination of two chiral drugs, namely, atenolol and chlorthalidone, is described. Prior investigation of the effect of different variables on the resolution of the enantiomers' peaks and the total run time represented by the retention time of the last eluted peak was conducted using face-centered composite design. Twenty-two experiments were carried out by varying the chiral stationary phase type as a categorical factor and mobile phase composition including the percentage of ethanol and percentage of diethylamine as continuous factors. According to the optimization process, a mobile phase consisting of hexane:ethanol:DEA:TFA (60:40:0.2:0.1%, v/v/v/v) pumped at flow rate 1 ml min -1 onto Lux-Cellulose 2 stationary phase was applied for the chiral separation and quantification of the drug combination at 230 nm. Application of the developed method to the pharmaceutical formulation of this combination was successfully performed, and satisfactory percentage of recoveries was obtained. The method was also fully validated following International Conference on Harmonization (ICH) guidelines. This method could be of high value and relevance for application in quality control laboratories., (© 2021 Wiley Periodicals LLC.)

Synthesis of three chiral 4,5-Di methyl ∆ 4 N-phenyl N-aryl imidazole-2-thione derivatives was obtained by the condensation reaction of thiourea derivatives with α-hydroxy ketone. The structure of these compounds has been characterized by using spectroscopic methods (UV, IR, 1 H NMR, and 13 C NMR). The 4,5-Di methyl ∆ 4 N-phenyl N-aryl imidazole-2-thiones display a chiral axis around the N-C bond linking between the nitrogen of the heterocyclic framework and the carbon of the aryl group. Screening on chiral analysis of the atropisomers of these derivatives was performed by high-performance liquid chromatography method on seven chiral selectors based on polysaccharides consisting of amylose and cellulose, namely, Chiralpak®AD, Chiralcel® OD, Chiralcel® OD-H, Chiralcel® OJ, Chiralcel® OD-3R, Chiralcel® OZ-3, and Chiralpak® AS-3R. The impact of ortho-substituent in the resolution of 4,5-Di methyl ∆ 4 N-phenyl N-aryl imidazole-2-thione derivatives was also studied in this work., (© 2021 Wiley Periodicals LLC.)

Chiral molecules in relation to particular biological roles are stereoselective. Enantiomers differ significantly in their biochemical responses in biological environment. Despite the current advancement in drug discovery and pharmaceutical biotechnology, the chiral separation of some racemic mixtures continues to be one of the greatest challenges, because the available techniques are too costly and time consuming for the assessment of therapeutic drugs in the early stages of development worldwide. Various nanoparticles became one of the most investigated and explored nanotechnology-derived nanostructures especially in chirality where several studies are reported to improve enantiomeric separation of different racemic mixtures. The production of surface-modified nanoparticles has contributed to these limitations in terms of sensitivity, accuracy, and enantioselectivity that can be optimized and therefore makes these surface-modified nanoparticles convenient for enantiomeric identification and separation., (© 2021 Wiley Periodicals LLC.)

A novel analytical method, based on high-performance liquid chromatography with a UV (HPLC-UV) detection system for the sensitive detection of a genotoxic impurity (GTI) 5-amino-2-chloropyridine (5A2Cl) in a model active pharmaceutical ingredient (API) tenoxicam (TNX), has been developed and validated. The HPLC-UV method was used for the determination of GTI 5A2Cl in API TNX. The compounds were separated using a mobile phase composed of water (pH 3 adjusted with orthophosphoric acid): MeOH, (50:50: v/v) on a C18 column (150 × 4.6 mm i.d., 2.7 μm) at a flow rate of 0.7 mL min-1. Detection was carried out in the 254 nm wavelength. Column temperature was maintained at 40°C during the analyses and 10 μL volume was injected into the HPLC-UV system. The method was validated in the range of 1-40 μg mL-1. The obtained calibration curves for the GTI compound was found linear with equation, y = 40766x - 1125,6 (R2 = 0.999). The developed analytical method toward the target compounds was accurate, and the achieved limit of detection and limit of quantification values for the target compound 5A2Cl were 0.015 and 0.048 μg mL-1, respectively. The recovery values were calculated and found to be between 98.80 and 100.03%. The developed RP-HPLC-UV analytical method in this research is accurate, precise, rapid, simple and appropriate for the sensitive analysis of target GTI 5A2Cl in model API TNX., (© The Author(s) 2020. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Background: Stilbene phytalexis (1,2-diphenyloethylen) and benzamide are beneficial for human health. To increase the stilbene ring activity, a new series of its derivatives containing benzamide structure was synthesized and evaluated for their in vitro antioxidant power., Methods: 1H nuclear magnetic resonance, mass spectroscopy, and chromatographic analyses were used to confirm the successful synthesis. The antioxidant properties were determined by the elimination of O 2 ˙-, HO˙ , DPPH˙ , ABTS+˙ radicals, total antioxidant status (TAS) and the ferric reducing antioxidant activities (TAC) measurements., Results: Stilbenebenzamide compounds showed a wide spectrum of antioxidant ability; however, their total antioxidant power was weaker than those of butylated hydroxytoluene (BHT), ascorbic acid, and resveratrol. The highest antiradical activity towards O 2 ˙ and HO˙ was shown by the compounds with structures containing amine group (SBEBA, SBA) (O 2 ˙: 37.7 - 38.0% and 40.8 - 43.5%, HO˙ : 29.8%, 28.7% inhibition, respectively) at1.25 mM concentration. The antiradical power of SBEBA (0.29) in DPPH˙ assay was lower than those of resveratrol (1.83), ascorbic acid (3.63) and BHT (4.09). The TAS values of the synthesized compounds ranged from 152.9±5.3 to 240.2±6.7μM trolox equivalent/gram (TE/g) and were much lower than those of BHT (1304±43.0), reservatrol (1360±29.0) and ascorbic acid (2782±39.7) μM TE/g. Similarly, the TAC values ranging from 29.7±0.9 to 41.5±1.6 μM TE were weaker than that of resveratrol (239.2 ±6.7 μM TE/g)., Conclusion: The results suggest that the presence of the hydroxyl group in the stilbene ring should be considered in the further design of stilbenebenzamide compounds to enhance their antioxidant activity., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Objective: This paper analyzes the potential outliers in the bioanalytical and clinical part of a bioequivalence study, the effect on bioequivalence decisions whether or not it is appropriate to eliminate them from the statistical evaluation of bioequivalence., Materials and Methods: The clinical part was a cross-over, two periods, two sequences bioequivalence study concerning two piroxicam formulations, on healthy subjects. A simulation study evaluated the influence of 10% errors on the percent bias of calculated concentrations from nominal ones., Results: In bioequivalence studies, it is not possible to distinguish between relevant types of outliers based only on statistical criteria. The "problem" is particularly acute when the omission of outliers leads to a bias in the decision concerning bioequivalence from rejection to acceptance. In such cases, there is the suspicion of subjective analysis and torture of data. The effect of analytical errors at high plasma levels was criticized for the calculated concentrations in the neighborhood of lower limit of quantification. Errors at low concentrations have a less significant effect. In the pharmacokinetic analysis, several types of outliers were shown: single points, curves, pairs of curves corresponding to the same subject, intrasubject ratios of areas under curves and maximum concentrations. These pharmacokinetic outliers could have had, at the same time, bioanalytical, physiological and physicochemical causes., Conclusion: Considering the results, it was proposed the following algorithm in the analysis of outlier data and outlier subjects in bioequivalence studies: evaluation of the implications of the decision concerning elimination of outliers on the decision concerning bioequivalence; application of the statistic tests for detection of outliers data; evaluations from the point of view of physiological pharmacokinetics, final decision concerning elimination of outliers.

Three stochastic microsensors based on graphite powder modified with three different oleamides: N-(2-piperidin-1-ylethyl)oleamide, N-(3,4-dihydroxyphenethyl)oleamide and N-(2-morpholinoethyl)oleamide, were designed, characterized, and used to assess DNA damage in cancer by assaying two biomarkers namely 8-nitroguanine and 8-hydroxy-2'-deoxyguanosine. The two biomarkers were determined from urine and whole blood samples. The characterization of the microsensors was done at two pHs 7.40 and 3.00. The best microsensor for the simultaneous determination of biomarkers in whole blood and urine samples was the one based on the graphite paste modified with N-(3,4-dihydroxyphenethyl)oleamide. The results indicated that the proposed microsensors can be reliably used for pattern recognition and quantitative determination of 8-nitroguanine and 8-hydroxy-2'-deoxyguanosine in whole blood and urine, and accordingly, for the assessment of DNA damage in cancer patients., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Adulteration of olive oil with the other cheap oils and fats plays an important role in economics and has nutritional benefits. In this work, metabolite profiling was performed using gas chromatography-mass spectrometry to identify and quantify animal fat (lard) adulteration in vegetable oil (olive oil). Principal component analysis could correctly identify and clustering olive oil, sunflower oil, sesame oil, lard, and adulterated samples through the changes in their fatty acid methyl esters (FAMEs) profile. A targeted metabolomics method was then optimized and validated through construction of calibration curves of known FAMSs in olive oil and lard. The method was presented high linearity (R 2  > 0.96) and good intra and inter day accuracy and precision (79-101 and 86-102% and 2-7 and 3-7, respectively) for determination of FAMEs. Afterwards the absolute concentration and relative percentage of FAMEs were successfully determined in 12 commercial olive oils and 3 lards samples. Methyl myristate, methyl palmitate, methyl oleate, and methyl stearate were selected as discriminant markers to identify and quantify lard adulteration even at a low level of lard (5%w/w), with errors less than 2% in the comparison of the absolute or relative concentrations of FAMEs using several statistical methods. The proposed methodology allowed us to quantify the FAMEs simultaneously and also could predict small amount of lard in the adulterated olive oil samples., Competing Interests: Conflict of interestThe authors declare that they have no conflict of interest., (© Association of Food Scientists & Technologists (India) 2020.)

One of the most common techniques for assessing the intestinal absorption characteristics of drugs is single-pass intestinal perfusion (SPIP) method. Metoprolol tartrate (MT, reference standard) and phenol red (PR, zero permeability marker) are the compounds that are normally used in SPIP studies. The aim of this study was to develop a reverse phase high-performance liquid chromatography (RP-HPLC) method combined with UV-detection for the simultaneous determination of MT and PR in the perfusion medium used in SPIP experiments. Elution was performed using a Restek Raptor C18 column (5 μm, 4.6 mm × 250) at a temperature of 25 °C. The mixture of the mobile phase consisted of (MeOH):(Phosphate buffer solution, PBS), (20 mM, pH 3.0 adjusted with ortho-phosphoric acid),(55:45, v/v). Flow rate and column temperature were set at 1.2 mL min -1 and 25 °C, respectively. MT and PR were injected as 20 µL into the HPLC system. UV detection was performed at 227 nm. The obtained retention times were reported as 2.89 and 3.80 min for MT and PR, respectively. The developed RP-HPLC method was validated according to Q2(R1) guideline of The International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH). The method was linear within the range of 2-50 μg mL -1 for PR and 10-75 μg mL -1 for MT. The developed RP-HPLC method was successfully applied on determination of MT and PR in perfusion medium. The developed method could be helpful for researchers working on in-situ rat intestinal permeability studies and it could be easily modified on further studies., Competing Interests: Declaration of Competing Interest Authors declare that there is no conflict of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

High-performance liquid chromatography (HPLC) and solid phase micro membrane tip extraction (SPMMTE) methods are developed for the simultaneous analysis of eleven cardiovascular drugs in human plasma. Iron nanoparticles were obtained by the green method, characterized by XRD, FT-IR, TEM, and EDS and utilized in SPMMTE for sample preparation. The mobile phase used was ammonium acetate buffer-methanol-acetonitrile (65:18:17) with a 1.0 mL/min flow rate at 260 nm detection. Column used was Sunshell C 18 150 × 4.6 mm, 2.6 µm. The values of k, α, and Rs were ranged from 040 to109.22, 1.20 to 2.67 and 1.0 to 26.18. SPMMTE and HPLC methods were fast, reproducible, precise, robust, economic and rugged for analysis of methyldopa, hydrochlorothiazide, prazosin hydrochloride, furosemide, labetalol, propranolol, valsartan, losartan potassium, diltiazem, irbesartan and spironolactone in human plasma. The recoveries (%) of methyldopa, hydrochlorothiazide, prazosin hydrochloride, furosemide, labetalol, propranolol, valsartan, losartan potassium, diltiazem, irbesartan, and spironolactone were 91.0, 85.2, 92.3, 90.4, 90.1, 85.6, 86.6, 86.2, 85.1, 86.6, and 85.7, respectively. These results showed that SPMMTE and HPLC methods can be applied to test the described drugs in several matrices., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

There is an increasing need to address the potential risks arising from combined exposures to multiple residues from pesticides in the diet. Pesticide residue-related pollution is a problem that arises because of the increased use of pesticides in agriculture to meet the growing demands of food production. In this study, pesticide residue data were obtained based on an optimized extraction method. For this purpose, we established a method based on quick, easy, cheap, effective, rugged, and safe (QuEChERS) extraction for simultaneous determination of imidacloprid (IMI) and acetamiprid (ACT) in pistachio nuts. The parameters influencing the QuEChERS method were the sample-to-water ratio and adsorbent amounts. As a result, both were optimized to improve the recovery of the analytes as well as the clean-up efficiency of the pistachio matrix. Our results indicated that a freeze-out step and use of primary and secondary amines as an adsorbent led to much cleaner chromatograms with lower baseline drift, without using graphitized carbon black and C 18 -based adsorbent, which reduced both cost and time of analysis. Following extraction, the pesticide residues were separated and quantified by reverse-phase HPLC. For validation purposes, recovery studies were carried out using a concentration range from 20 to 2500 μg/L at nine levels. The suitable linearity, precision, and accuracy were obtained with HPLC-UV with recoveries of 70.37%-89.80% for IMI and 81.05%-113.57% for ACT, with relative standard deviations <12%. The validated method was successfully applied to the analysis of pistachio samples collected from a field trial to estimate maximum residue limits. There was no significant health risk for consumers via pistachio consumption., (© 2019 John Wiley & Sons, Ltd.)

Background: A series of eight new flavone derivatives containing a piperazine chain with different substitution were synthesized and their structures were determined., Methods: Their antiradical and antioxidant activities were evaluated using superoxide anion radical, hydroxyl radical, 2,2-diphenyl-1-picrylhydrazyl radical, 2,2'-azino-di(3-ethylbenzthiazoline sulphonate) radical cation (ABTS + ) scavenging (as measure total antioxidant status TAS), ferric reducing antioxidant power (TAC), and hydrogen peroxide decomposition. The antioxidant activities of the synthesized compounds were compared with standard antioxidants trolox, ascorbic acid, butylated hydroxytoluene (BHT) as positive controls, reference antibiotics (doxycycline, dicloxacillin), and medicinal plants (Menthae piperita, Cistus incanus). Chemiluminescence, spectrophotometry, electron spin resonance (ESR) spectroscopy in conjunction with 5,5-dimethyl-1-pyrroline-1-oxide (DMPO) as the spin trap were the measurement techniques., Results: The results show that the synthesized compounds exhibit weak, albeit a wide spectrum of antiradical and antioxidant activities. The TAS values were measured as trolox equivalents, ranging from 209.6 ± 6.1 to 391.1 ± 8.2 µM TE/g; the TAC values were in ranges from 10.8 ± 0.5 to 49.5 ± 0.5 µM TE/g being higher than that of dicloxacillin (241.0 ± 16.5 and 9.73 ± 0.8 µM TE/g, respectively), but lower than ascorbic acid, BHT, doxycycline, and medicinal plants. Best antioxidant activities were found for the piperazinyl analogues with methoxy group on phenyl piperazine ring., Conclusion: We suggest that the synthesized compounds may be used as lead molecules for optimization of molecular structure to maximize the antioxidant potency., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Aim: A new, accurate and sensitive reversed-phase high-performance liquid chromatography (RP-HPLC) as an analytical method for the quantitative determination of eight antifungal drugs in spiked human plasma has been described optimized and validated., Materials and Methods: The analyzed compounds were voriconazole (VOR), luliconazole (LUL), clotrimazole (CLO), tioconazole (TIO), posaconazole (POS), ketoconazole (KET), sertaconazole (SER) and terconazole (TER)., Results: The separation of the analyzed compounds was conducted using a novel pentabromobenzyl column known as COSMOSIL PBB-R (150 mm × 4.6 mm I.D., particle size 5 μm). The analysis of the studied drugs was determined within 14 min using a diode array detector and the mobile phase consisted of: 10 mM potassium dihydrogen phosphate buffer (pH 2.1): Methanol (2: 98 v/v). A linear response was observed for all compounds in the range of concentration studied. Sample preparation was done through liquid-liquid extraction using diethyl ether., Conclusion: This proposed method was validated in terms of linearity, limit of quantification, limit of detection, accuracy, precision and selectivity. The method was successfully applied for the determination of these drugs in their pharmaceutical formulations and in human plasma samples., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

The commercial value of cashew nut shell liquid (CNSL) has become a cornerstone of the agrowaste industry. It is the by-product of the cashew industry and has an 1/8 inch thickness of soft honeycomb structure. CNSL contains phenolic lipids with aliphatic chains such as anacardic acid, cardanol, cardol and methyl cardol, and their derivatives. The developed GC-MS method is rapid, accurate and selective using a selected derivatizing reagent, namely N-methyl-N-(trimethylsilyl)-trifluoroacetamide that was previously diluted 1:1% with anhydrous pyridine. The proposed GC-MS method was applied for the analysis of different CNSL samples. The results showed that all classes of CNSL compounds were detected. The four alkyl phenols were detected with their different alkyl sidechains without any interference. This method is also specified for the detection of fatty acids of saturated and unsaturated chains. Silylation did not cause any alteration in the chemical structure of CNSL compounds regardless of esterification action. Silylation is considered a safe derivatizing agent compatible with GC chromatography and specific for all volatile and nonvolatile polar and nonpolar CNSL compounds that could be detected in CNSL samples., (© 2019 John Wiley & Sons, Ltd.)

Chiral stationary phases are conveniently used for enantiomeric separation of drugs by liquid chromatography. Consumption of large volumes of hazardous solvents is considered as a common challenge for the sustainability of this technique. To this end, a columnar chromatography has been adopted using 50-mm-length stationary phases. The study comprised five Phenomenex Lux cellulose- and amylose-based columns for the separation of guaifenesin (GUA) enantiomers. In addition, an experimental design was used to optimize the gradient profile for the separation of racemic GUA and ambroxol HCl (AMB) binary mixture. The chromatographic method was achieved using Lux Cellulose-1 (50 × 4.6 mm) as a chiral stationary phase and ethanol/water as a mobile phase with linear gradient elution of 20% to 70% ethanol in 6 minutes at a flow rate of 1.0 mL min -1 and UV detection at 270 nm. Linearity ranges were found to be 50 to 1000 μg mL -1 and 15 to 450 μg mL -1 for each GUA enantiomer and AMB, respectively. Environmental, health and safety tool was used to assess and compare greenness of the proposed and reported methods. Short column indeed reduces the environmental impact by decreasing waste by about 60% and utilizing only 1-mL ethanol in the mobile phase. The proposed method is a safer alternative for the simultaneous determination of drugs in their combined pharmaceutical formulation. The method has been validated and compared favorably with a reported one., (© 2019 Wiley Periodicals, Inc.)

A quality-by-design approach was adopted for enantioseparation of atenolol on Vancomycin and Teicoplanin-based chiral stationary phases using reversed phase (RP) mode and polar ionic mode (PIM), respectively to account for major forces involved in enantiorecognition of β-blockers on macrocyclics. A fractional factorial screening design for the two modes; followed by a central composite optimization design and regression analysis were able to point out critical factors and chromatographic responses and robust surface of the design. Within the studied range of flow the optimal was 0.3 mL/min for Chirobiotic T and 1 mL/min for Chirobiotic V. In PIM, a composition of 100% methanol was mandatory to compromise between best separation and least retention with equal amounts of the acid and base modifiers for enantiomers of atenolol, as model drug in addition to metoprolol and pindolol as structurally related compounds for possible extrapolation of results on members of the same class. However, in RP mode, only triethylamine acetate was needed as buffer for atenolol enantiomers. Chiral recognition of atenolol in both elution modes, further confirmed via extrapolation of the models on the two other β-blockers showed that ionic interactions rather than any other forces governed chiral recognition on the two macrocyclic stationary phases in both modes., (© The Author(s) 2019. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

The body of evidence from the past three decades demonstrates that oxidative stress can be involved in several diseases. This study aims to summarise the current state of knowledge on the association between oxidative stress and the pathogenesis of some characteristic to the biological systems diseases and aging process. This review also presents the effect of physical activity on redox homeostasis. There is strong evidence from studies for participation of reactive oxygen and nitrogen species in pathogenesis of acute and chronic diseases based on animal models and human studies. Elevated levels of pro-oxidants and various markers of the oxidative stress and cells and tissues damage linked with pathogenesis of cancer, atherosclerosis, neurodegenerative diseases hypertension, diabetes mellitus, cardiovascular disease, atherosclerosis, reproductive system diseases, and aging were reported. Evidence confirmed that inflammation contributes widely to multiple chronic diseases and is closely linked with oxidative stress. Regular moderate physical activity regulates oxidative stress enhancing cellular antioxidant defence mechanisms, whereas acute exercise not preceded by training can alter cellular redox homeostasis towards higher level of oxidative stress. Future studies are needed to clarify the multifaceted effects of reactive oxygen/nitrogen species on cells and tissues and to continue study on the biochemical roles of antioxidants and physical activity in prevention of oxidative stress-related tissue injury.

A simple, fast and highly sensitive RP-UPLC-MS/MS method was developed and validated for the simultaneous determination of sofosbuvir (SR) and its metabolite GS331007 in human plasma using ketotifen as an internal standard (IS). The separation was achieved on Acquity UPLC BEH C 18 (50 × 2.1 mm, i.d. 1.7 µm, Waters, USA) column using acetonitrile:5 mM ammonium formate:0.1% formic acid (85:15:0.1% v / v / v ) as a mobile phase at a flow rate of 0.35 mL/min in an isocratic elution. The Xevo TQD UPLC-MS/MS was operated under the multiple-reaction monitoring mode using positive electrospray ionization. Extraction with dichloromethane was used in the sample preparation. Method validation was performed as per the Food and Drug Administration (FDA) guidelines and the calibration curves of the proposed method were found to be linear in the range of 1-1000 ng/mL for SR and in the range of 10-1500 ng/mL for its metabolite (GS331007) with an elution time of 1.83 min. All validation parameters were within the acceptable range according to the bioanalytical methods validation guidelines. Furthermore, the obtained results of matrix effects indicate that ion suppression or enhancement from human plasma components was negligible under the optimized conditions. The proposed method can be applied in high-throughput analysis required for pharmacokinetic and bioequivalence studies in human samples.

In this study, the concentrations of lead, cadmium and manganese were determined in horse mackerel (Trachurus mediterraneus) and whiting (Merlangius merlangus euxinus) that were caught in the Sea of Marmara. These are commonly consumed fish species in this region. Fish were provided by a fishermen quarterly between March 2013 and December 2013 and, separated according to size (small, medium and large). Pb(II), Cd(II) and Mn(II) levels were determined using the wet digestion method by Graphite furnace atomic atomic absorption spectrophotometer. According to this study, for horse mackerel, the highest concentration of lead, cadmium, and manganese was 6.69 µg kg -1 (September), 5.24 µg kg -1 (March) and 9.24 µg kg -1 (June), respectively. For whiting, the highest concentration of lead, cadmium, and manganese was 2.25 µg kg -1 (June), 0.263 µg kg -1 (September) and 10.4 µg kg -1 (June), respectively. These heavy metal levels in fish were found to be acceptable for human consumption according to World Health Organization border values.

An easily performed, specific, sensitive, rapid, reliable and inexpensive procedure for the spectrofluorometric quantitation of ascorbic acid was proposed using acriflavine as a fluorescence quenching reagent. The procedure was based on the determined quenching effect of ascorbic acid on the natural fluorescence signal of acriflavine and the reaction between ascorbic acid and acriflavine in Britton-Robinson buffer solution (pH 6) to produce an ion-associated complex. The reduction in acriflavine fluorescence intensity was detected at 505 nm, while excitation occurred at 265 nm. The relationship between quenching fluorescence intensity (∆F) and concentration of ascorbic acid was linear (R 2  = 0.9967) within the range 2-10 μg/ml and with a detection limit of 0.08 μg/ml. No significant interference was detected from other materials often found in pharmaceutical nutritional tablets. The obtained results were compared with those from high-performance liquid chromatography and appeared in good agreement, with no important differences in precision or accuracy. The proposed spectrofluorimetric method was used to determine the amount of ascorbic acid in a number of commercial pharmaceutical nutritional supplement tablets with a 95% confidence performance., (© 2019 John Wiley & Sons, Ltd.)

The present work describes a capillary electrophoretic (CE) generic strategy used for chiral enantioseparation of Fluconazole (as an example of acidic drugs) and donepezil (as an example of basic drugs). Several modified cyclodextrins (CDs) were applied for enantioseparation of racemates such as highly sulfated α, γ CDs, hydroxyl propyl-β-CD, and sulfobutyl ether-β-CD. The starting screening conditions consist of 50 mM phosphate-triethanolamine buffer at pH 2.5, an applied voltage of 15 kV, and a temperature of 25 °C. The design of experiment (DOE) was based on a full factorial design of the crucial two factors (pH and %CD) at three levels, to make a total of nine (3 2 ) experiments with high, intermediate, and low values for both factors. Evaluation of the proposed strategy pointed out that best resolution was obtained at pH 2.5 for the investigated racemates using low percentages of HS-γ-CD, while SBE-β-CD was the most successful chiral selector offering acceptable resolution, with best separation at low pH values and at higher %CD within 10 min runtime. Regression study showed that the linear model shows a significant lack of fit for all chiral selectors, anticipating that higher orders of the factors are most likely to be present in the equation with possible interactions.

Immunoassay technique performs a fast, simple, reliable, and sensitive analysis of different compounds, being applied in several areas of interest such as clinical analysis for medical diagnosis, as well as in environmental analysis, and food quality control. The latest research activities in this field are represented by the attempts to achieve a low limit of detection by developing of new signal amplification strategies, eliminate the interferences, and decrease the cost of analysis.

The enantioseparation of three fluoroquinoline antibacterial drugs, namely, flumequine, ofloxacin and lomefloxacin using high-performance liquid chromatography was optimized on seven polysaccharide-derived chiral stationary phases, namely, Chiralpak® IB, chiralpak® IA, Chiralpak® AD, Chiralcel® OJ, Chiralcel® OD, Chiralcel® OD-H and Chiralcel® OZ-3 and applying different mobile phases in isocratic mode is described. The role of addition of organic additives was also investigated. A baseline separation of flumequine, ofloxacin and lomefloxacin enantiomers was achieved. Parameters influencing enantioseparation including mobile phase, organic additive and chemical nature of the chiral selector found to be highly influencing on the enantiomeric separation were investigated. Chiral recognition mechanism(s) are also presented.

Aim: Synthesis of novel 2(2-hydroxyphenyl) pyrimidine/benzothiazole piperazinyl-substituted flavones end evaluate their antioxidant activity., Results: Six novel 2-(2-hydroxyphenyl) pyrimidine/benzothiazole-substituted flavones were synthesized, their structures were confirmed by elementary and spectral analyses. The compounds were evaluated for their in vitro antioxidant potency by employing various antioxidant assays., Conclusion: All tested compounds acted as scavengers of free radicals like hydroxyl (15-45%), 2,2-diphenyl-1-picrylhydrazyl • (17-48%) at 1.25 and 0.5 mM concentrations respectively. The total antioxidant status activity values of the compounds ranged from 234.1 to 464.1 μm trolox equivalent/g, the total antioxidant capacity - from 24.9 to 52.7 μm trolox equivalent per gram. Compounds incorporating the benzothiazole group on the piperazine ring were more effective antioxidants than those with the 2-(2-hydroxyphenyl) pyrimidine group.

Multidimensional gas chromatography (MDGC) is well-established GC method used for a diverse range of applications. Enantioselective MDGC (enantio-MDGC) has been suggested as the method of preference for the separation of extremely overlapping enantiomers. An extensive number of literatures describe enantio-MDGC of polychlorinated biphenyls, essential oils and flavor and fragrance and amino acids were reported. In this review, the applications of MDGC approaches both, heart cutting GC-GC and comprehensive GC × GC in chiral analysis is presented. Since the application of these techniques in this filed is very broad so it will be divided into sections according to the type of the compounds.