Simultaneous Quantification of Two Neonicotinoids Using QuEChERS-LC-MS/MS in Moroccan Spearmint (Mentha Spicata.L): Qualimetry of the Method by Uncertainty Estimation Using Generalized Pivotal Quantities Approach and Monte Carlo Simulation.

BACKGROUND: Neonicotinoids (NEOs) are used for the phytosanitary treatment of Mentha Spicata.L crops, and this practice requires precise control of these harmful substances at very low concentrations. OBJECTIVE: The objective of this study is to apply an approach allowing simultaneously validation and evaluation of measurement uncertainty based on total error methodology, in order to accurately quantify the presence of two NEOs in Mentha Spicata.L utilizing a Quick, Easy, Cheap, Effective, Rugged, and Safe (QuEChERS)-LC-MS/MS methodology. METHODS:  The quantification of imidacloprid and acetamiprid employing a QuEChERS extraction method, coupled with LC-MS/MS, ensuring the accuracy of the analytical method and managing the risks associated with its routine use. A complete and exhaustive validation approach based on the "ß-content, γ-confidence" tolerance interval was used for the uncertainty assessment, using the generalized pivot quantity (GPQ) concept and Monte Carlo simulation, which avoids the need for additional data while achieving intermediate precision for each concentration level within predetermined acceptable limits. RESULTS: The validation procedure is based on the choice of a quadratic model for the two NEOs, allowing the validation of acetamiprid and imidacloprid by LC-MS/MS assay within the range of working concentration. The flexibility of the uncertainty profile intervals was demonstrated with a variation in ß-content values (66.7, 80, and 90%) and risk values (10 and 5%), which remained within the acceptability limits of 20%, and the relative expanded uncertainty did not exceed 15 and 11%. CONCLUSION: A QuEChERS-LC-MS/MS method for the analysis of two NEOs has been successfully fully validated using the uncertainty profile strategy. HIGHLIGHTS: Implementation of an overall validation strategy, which involves both the validation and uncertainty assessment known as the uncertainty profile, for the quantification of two important NEOs in Mentha Spicata.L using QuEChERS-LC-MS/MS. This qualimetric approach has been conducted by computing the measurement uncertainty of the method utilizing data from analytical validation under conditions of intermediate precision at each level of concentration without additional effort. After that we have demonstrated the flexibility of this strategy for the LC-MS/MS quantification of acetamiprid and imidacloprid, using a decision tool that enables the choice and modification of ß-content and γ-confidence values.

QSAR modeling for cytotoxicity of sulfur-containing Shikonin oxime derivatives targeting HCT-15, MGC-803, BEL-7402, and MCF-7 cell lines.

Targeting cancer cells through drug-based treatment or combination therapy protocols involving chemical compounds can be challenging due to multiple factors, including their resistance to bioactive compounds and the potential of drugs to damage healthy cells. This study aims to investigate the relationship between the structure of novel sulfur-containing shikonin oxime compounds and the corresponding cytotoxicity against four cancer types, namely colon, gastric, liver, and breast cancers, through computational chemistry tools. This investigation is suggested to help build insights into how the structure of the compounds influences their activity and understand the mechanisms behind it and subsequently might be used in multi-cancer drug design process to propose novel optimized compounds that potentially exhibit the desired activity. The findings showed that the cytotoxic activity against the four cancer types was accurately predictable (R2 > 0.7, NRMSE <20%) by a combination of search and machine learning algorithms, based on the information on the structure of the compounds, including their lipophilicity, surface area, and volume. Overall, this study is supposed to play a crucial role in effective multi-cancer drug design in cancer research areas.

Intra-GUM comparisons for the estimation of measurement uncertainty: Application to a chromatographic assay of four statins in a dry form.

The chromatographic method (HPLC) is well-known for its dependability and precision in pharmaceutical analyses for assessing the quality and efficacy of drug products. However, the characteristics of the HPLC method make sense only after a careful evaluation of the measurement uncertainty. Nevertheless, it has been observed that precise identification of the sources of uncertainty resulting from the operational mode using the HPLC technique to assess their standard uncertainty based on the ISO-GUM approach is not obvious. Because of our extensive bibliographic search, we noticed that many studies published on the estimate of the uncertainty in chromatographic methods (HPLC) using the Eurachem/Citac guide are somewhat diverse in their use of this approach. The documentary research revealed four mathematical models namely, GUM1, GUM2, GUM3, and GUM4 that are most used to estimate the measurement uncertainty of the HPLC technique. Hence, a comparison between the four GUM mathematical models was carried out graphically and statistically using one-way ANOVA followed by Tuckey and Scheffe tests. The comparison results show a significant difference, which may create confusion in the reporting of measurement results as well as problems in making sound decisions. This leads to the suggestion that alternative approaches, such as the approach of a total error or ISO 11325, be used to check the ISO-GUM method's calculations of measurement uncertainty.

The Uncertainty Profile Used for Full Validation of the HPLC Method to Determine 22 Azo Amines in Fabrics.

BACKGROUND: Azo dyes are synthetic dyes that can degrade to carcinogenic amines, therefore determining their exact concentration is crucial. OBJECTIVE: The purpose of this study is to demonstrate that an HPLC method may be used to quantify 22 azo dye amines in a textile matrix. METHODS: The HPLC-DAD (Diode Array Detector) technique for measuring 22 amines in a textile matrix was tested using a new graphical statistical strategy based on the building of ß-content, γ-confidence tolerance intervals, which allows for good qualimetry of analytical procedures. In this way, we established the approach's ability to perform a full validation of the analytical technique as well as its ability to estimate measurement uncertainty in a simple and uncomplicated way with minimum effort, utilizing only the data collected during the analytical validation. RESULTS: The findings suggest that this technique can properly assess the validity of the HPLC method for simultaneous determination of 22 amines, with 67-90% of compliance results falling within acceptable limits. CONCLUSION: Using the uncertainty profile methodology, the full validation of an HPLC method for the determination of 22 azo amines in a textile matrix was successfully established. HIGHLIGHTS: The development and evaluation of an efficient HPLC technique for the simultaneous determination of 22 azo amines in a textile matrix have been completed. The total reliability of the analytical procedure was established by evaluating its measurement uncertainty at each concentration level using the suggested uncertainty profile approach and confirming proportions 67 to 90% of compliance.

The synergic approach between machine learning, chemometrics, and NIR hyperspectral imagery for a real-time, reliable, and accurate prediction of mass loss in cement samples.

Alternative and non-destructive analytical methods that predict analyte concentration accurately and immediately in a specific matrix are becoming vital in the analytical chemistry domain. Here, a new innovative and rapid method of predicting mass loss of cement samples based on a combination of Machine Learning (ML) and the emerging technique called Hyperspectral Imaging (HSI) is presented. The method has proved its reliability and accuracy by providing a predictive ML model, with satisfactory best validation scores recorded using partial least squared regression, with a reported ratio of performance to inter-quartile distance and root mean squared error of 12,89 and 0.337, respectively. Moreover, the possibility of optimizing and boosting the performance of the method by optimizing the predictive model performance has been suggested. Therefore, a features selection approach was conducted to disqualify non-relevant wavelengths and stress only relevant ones in order to make them the only contributors to a final optimized model. The best selected features subset was composed of 28 wavelengths out of 121, found by applying genetic algorithm combined to partial least squares regression as a feature selection method, on spectra preprocessed consecutively by the first-order savitzky-golay derivative calculated with 7-point quadratic SG filter, and multiplicative scatter correction method. The overall results show the possibility of combining HSI and ML for fast monitoring of water content in cement samples.

The Flexibility of ß-Content, γ-Confidence Tolerance Intervals to Qualimetry a Simultaneous 22 Aromatic Amines Derived from Azo Dyes in Fabric Using a Sensitive GC-MS Technique.

BACKGROUND: Azo dyes are among the most widely used dyes in the textile industry, releasing a series of carcinogenic aromatic amines that can be absorbed through the skin. OBJECTIVE: This work aims to show that 22 azo dye amines in a textile matrix can be quantified using a GC-MS method. METHODS: Based on the notion of total error and ß-content, γ-confidence tolerance intervals (ß,γ-CCTI), a chemometric approach known as the "uncertainty profile" has been used to completely validate a GC-MS method for the simultaneous assay of 22 azo amines in fabrics. According to International Organization for Standardization (ISO) in ISO 17025 guidelines, analytical validation and measurement uncertainty estimates have evolved to be two main principles for ensuring the accuracy of analytical results and controlling the risk associated with their use. RESULTS: The calculated tolerance intervals allowed for the determination of the uncertainty limits at each concentration level. These limits when compared to the acceptable limits show that a significant portion of the expected outcomes is in conformity. Additionally, the relative expanded uncertainty values, calculated with a proportion of 66.7% and a 10% risk, do not exceed 27.7, 12.2, and 10.9% for concentration levels 1, 15, and 30 mg/L, respectively. CONCLUSION: The capability and flexibility of the ß-content, γ-confidence intervals have been established through the use of this innovative approach to carrying out qualimetry of the GC-MS method depending on the behavior, required conformity proportion, and acceptable tolerance limits of each amine. HIGHLIGHTS: An efficient GC-MS technique for the simultaneous determination of 22 azo amines in a textile matrix has been developed. Analytical validation using a new strategy based on the uncertainty concept is reported, uncertainty associated to measurement results is estimated, and the applicability of our approach to the GC-MS method is investigated.

An Overall Validation Approach Based on ß-Content, γ-Confidence Tolerance Interval, and Uncertainty Profile: Application to LC-MS/MS Quantification of Carbendazim in Drinking Water.

BACKGROUND: Carbendazim is a fungicide which can seep into the water supply, presenting a public health risk, and therefore the accurate trace determination of this substance is very important. OBJECTIVE: The purpose of the study is to take a top-down analytical validation approach in order to determine the amount of carbendazim in drinking water by using an SPE-LC-MS/MS technique. METHODS: Quantification of carbendazim using solid-phase extraction coupled with LC-MS/MS was used in order to ensure the accuracy of the analytical method and to control the risk of its routine application. An overall validation methodology based on two-sided tolerance interval type ß-content, γ-confidence has been applied for the validation and estimation of uncertainty by building a decision graphical tool called the "uncertainty profile" by using the statistical process known as the Satterthwaite approximation with no recourse to additional data by satisfying intermediate precision condition for each concentration level within the acceptance limits fixed in advance. RESULTS: The process of validation is based on the selection of a linear weighted 1/X model enabling validation of the carbendazim dosage using LC-MS/MS in the range of working concentrations as the ßγ-CCTI fell inside acceptable limits of ±10%, and the relative expanded uncertainty did not surpass 7% regardless of the ß values (66.7, 80, and 90%) and the 1- γ = risk (10 and 5%). CONCLUSION: The application of the uncertainty profile approach for full validation of a SPE-LC-MS/MS assay for the quantification of carbendazim has been successfully achieved. HIGHLIGHTS: Implementation of a full validation strategy based on validation and measurement uncertainty with no additional effort using data from analytical validation under intermediate precision conditions at each level of concentration for carbendazim quantification in drinking water using SPE-LC-MS/MS. So we have shown the flexibility of this approach for carbendazim assay by LC-MS/MS. Indeed, It provides an efficient decision-making tool that allows selection and modification of ß-content and γ-confidence values.

Characterization of Ziziphus lotus' Activated Carbon and Evaluation of Its Adsorption Potential.

This study aims to prepare activated carbon from an interesting biomaterial, corresponding to the cores of Ziziphus lotus, for the first time to the best of our knowledge, according to a manufacturing process based on its chemical and thermal activation. These cores were chemically activated by sulfuric acid for 24 h and then carbonized at 500°C for 2 hours. The obtained activated carbon was characterized by scanning electron microscopy, X-ray diffraction, Fourier transform infrared spectroscopy, and Brunauer-Emmett-Teller (BET) analysis. The adsorption of methylene blue (MB) on the activated carbon was evaluated, by Langmuir and Freundlich models examination, in order to explain the adsorption efficiency in a systematic and scientific way. Moreover, pseudo-first-order and pseudo-second-order kinetic models were used to identify the mechanisms of this adsorption process. The characterization results showed an important porosity (pore sizes ranging from 10 to 45 µm), a surface structure having acid groups and carboxylic functions, and a specific surface of 749.6 m2/g. Results of the MB adsorption showed that this process is very fast as more than 80% of MB is adsorbed during the first 20 minutes. In addition, increasing the contact time and temperature improves the MB removal process efficiency. Moreover, this adsorption's kinetic modeling follows the pseudo-second-order model. Furthermore, data on the adsorption isotherm showed a maximum adsorption capacity of 14.493 mg/g and fit better with the Langmuir model. The thermodynamic parameters (∆G0, ∆S0, and ∆H0) indicate that the adsorption process is endothermic and spontaneous. Therefore, Ziziphus lotus can be used as a low-cost available material to prepare a high-quality activated carbon having a promising potential in the wastewater treatment.

Seasonal Paspalum vaginatum Physiological Characteristics Change with Agricultural Byproduct Biochar in Sandy Potting Soil.

A plastic pot open-air trial was conducted with the Paspalum vaginatum (seashore paspalum) using different rates of biochar or compost addition to sandy loam soil and two water treatments (60% and 20% of the water-holding capacity of the control) during three seasons (winter, spring, and summer). Paspalum growth, physiological characteristics, and physicochemical properties of soil were investigated. The effect of biochar on soil properties was assessed using factor analysis of mixed data (FAMD). Additionally, multiple factorial designs (MFA) were used to examine the impact of three biochars on physiological functions. Peanut hull biochar application increased soil fertility and chlorophyll concentration of paspalum leaves significantly compared to the other biochars. Physiological characteristics were significantly improved with peanut hull biochar under summer compared to winter and spring due to the accumulation of nutrients in the soil by the decomposition of biochar. The application rate of the three biochars reduced the water requirements of paspalum. The best result was obtained by incorporating 6% peanut hull biochar into the soil, which resulted in better soil quality and healthy grass in dryland conditions while using 47.5% less water. These findings can be suitable for golf managers and can serve as a solution for dry zones.

Application of Design Space, Uncertainty, and Risk Profile Strategies to the Development and Validation of UPLC Method for the Characterization of Four Authorized Phosphodiesterase Type 5 Inhibitors to Combat Counterfeit Drugs.

BACKGROUND: Counterfeit medicines are an increasing scourge that are difficult to identify and they have become industrialized and widespread through highly organized illegal channels. OBJECTIVE: This research aims to develop a robust method to determine four phosphodiesterase type-5 inhibitors in counterfeit drugs based on ultra-performance liquid chromatography. METHOD: Experimental design methodology (DOE) and design space (DS) recommended by ICH Q8 were used side-by-side in the development phase to define the optimal parameters as well as the robustness of the chromatographic method. Moreover, both the uncertainty and risk profile derived from the ß-content and γ-confidence tolerance interval were investigated during the validation phase to examine the performance of this method. RESULTS: Successful chromatographic results, in a high resolution between the four active ingredients and an optimal analysis time of less than 1.6 min, were achieved at the end of the optimization phase. In addition, validation results show a low risk of future measurements outside acceptance limits set at 5%. CONCLUSIONS: Our procedure was successfully applied in the routine phase to identify 23 illicit formulations of an erectile dysfunction drug. HIGHLIGHTS: An efficient method for the characterization of 4 authorized phosphodiesterase in less than 1.6 min was established. A DS approach was applied to test the performance of this analytical method during analytical development. A risk profile was then carried out to approve the validity of the analytical method through the uncertainty profile approach.

Validation and Measurement Uncertainty Assessment of a Microbiological Method Using Generalized Pivotal Quantity Procedure and Monte-Carlo Simulation.

Recently, a novel and effective statistical tool called the uncertainty profile has been developed with the purpose of graphically assessing the validity and estimating the measurement uncertainty of analytical procedures. One way to construct the uncertainty profile is to compute the ß-content, γ-confidence tolerance interval. In this study, we propose a tolerance interval based on the combination of the generalized pivotal quantity procedure and Monte-Carlo simulation. The uncertainty profile has been applied successfully in several fields. However, in order to further confirm its universality, this newer approach has been applied to assess the performance of an alternative procedure versus a reference procedure for counting of Escherichia coli bacteria in drinking water. Hence, the aims of this research were to expose how the uncertainty profile can be powerfully applied pursuant to ISO 16140 standards in the frame of interlaboratory study and how to easily make a decision concerning the validity of the procedure. The analysis of the results shows that after the introduction of a correction factor, the alternative procedure is deemed valid over the studied range because the uncertainty limits lie within the acceptability limits set at ±-0.3 log unit/100 ml for a ß = 66.7% and γ = 90%.

Combined treatment of Thymus vulgaris L., Rosmarinus officinalis L. and Myrtus communis L. essential oils against Salmonella typhimurium: Optimization of antibacterial activity by mixture design methodology.

To increase the sensibility of Salmonella typhimurium strain, a mixture of Thymus vulgaris L. (T. vulgaris L.), Rosmarinus officinalis L. (R. officinalis L.) and Myrtus communis L. (M. communis L.) essential oils (EOs) was used in combined treatment by experimental design methodology (mixture design). The chemical composition of EOs was firstly identified by GC and GC/MS and their antibacterial activity was evaluated. The results of this first step have shown that thymol and borneol were the major compounds in T. vulgaris and M. communis L. EOs, respectively, while 1,8-cineole and α-pinene were found as major compounds in R. officinalis L. The same results have shown a strong antibacterial activity of T. vulgaris L. EO followed by an important power of M. communis L. EO against a moderate activity of R. officinalis L. EO. Besides, 1/20 (v/v) was the concentration giving a strain response classified as sensitive. From this concentration, the mixture design was performed and analyzed. The optimization of mixtures antibacterial activities has highlighted the synergistic effect between T. vulgaris L. and M. communis L. essential oils. A formulation comprising 55% of T. vulgaris L. and 45% of M. communis L. essential oils, respectively, can be considered for the increase of Salmonella typhimurium sensibility.

Chemometric investigation of light-shade effects on essential oil yield and morphology of Moroccan Myrtus communis L.

BACKGROUND: To investigate the effect of environmental factors such as light and shade on essential oil yield and morphological traits of Moroccan Myrtus communis, a chemometric study was conducted on 20 individuals growing under two contrasting light environments. RESULTS: The study of individual's parameters by principal component analysis has shown that essential oil yield, altitude, and leaves thickness were positively correlated between them and negatively correlated with plants height, leaves length and leaves width. Principal component analysis and hierarchical cluster analysis have also shown that the individuals of each sampling site were grouped separately. The one-way ANOVA test has confirmed the effect of light and shade on essential oil yield and morphological parameters by showing a statistically significant difference between them from the shaded side to the sunny one. Finally, the multiple linear model containing main, interaction and quadratic terms was chosen for the modeling of essential oil yield in terms of morphological parameters. CONCLUSIONS: Sun plants have a small height, small leaves length and width, but they are thicker and richer in essential oil than shade plants which have shown almost the opposite. The highlighted multiple linear model can be used to predict essential oil yield in the studied area.

Large-scale retrospective evaluation of regulated liquid chromatography-mass spectrometry bioanalysis projects using different total error approaches.

The current approach in regulated LC-MS bioanalysis, which evaluates the precision and trueness of an assay separately, has long been criticized for inadequate balancing of lab-customer risks. Accordingly, different total error approaches have been proposed. The aims of this research were to evaluate the aforementioned risks in reality and the difference among four common total error approaches (ß-expectation, ß-content, uncertainty, and risk profile) through retrospective analysis of regulated LC-MS projects. Twenty-eight projects (14 validations and 14 productions) were randomly selected from two GLP bioanalytical laboratories, which represent a wide variety of assays. The results show that the risk of accepting unacceptable batches did exist with the current approach (9% and 4% of the evaluated QC levels failed for validation and production, respectively). The fact that the risk was not wide-spread was only because the precision and bias of modern LC-MS assays are usually much better than the minimum regulatory requirements. Despite minor differences in magnitude, very similar accuracy profiles and/or conclusions were obtained from the four different total error approaches. High correlation was even observed in the width of bias intervals. For example, the mean width of SFSTP's ß-expectation is 1.10-fold (CV=7.6%) of that of Saffaj-Ihssane's uncertainty approach, while the latter is 1.13-fold (CV=6.0%) of that of Hoffman-Kringle's ß-content approach. To conclude, the risk of accepting unacceptable batches was real with the current approach, suggesting that total error approaches should be used instead. Moreover, any of the four total error approaches may be used because of their overall similarity. Lastly, the difficulties/obstacles associated with the application of total error approaches in routine analysis and their desirable future improvements are discussed.