Analysis Method Research Articles

ROBUST GEOGRAPHICALLY WEIGHTED REGRESSION WITH LEAST ABSOLUTE DEVIATION (LAD) ESTIMATION AND M-ESTIMATION ON GRDP OF WEST JAVA PROVINCE

Geographically Weighted Regression (GWR) is an analytical method for data that contains spatial heterogeneity effects. However, parameter estimation in the GWR model has a weakness, namely it is prone to outliers and can cause the parameter estimation to be biased. This can be overcome by the Robust Geographically Weighted Regression (RGWR) method which is more robust against the presence of outliers. This method is suitable for Gross Regional Domestic Product (GRDP) data in West Java Province, which contains outliers and also has spatial effects. The data used in this study are secondary data obtained from the Central Statistics Agency (BPS) of West Java Province. The purpose of this study is to compare the Robust Geographically Weighted Regression (RGWR) method with the Least Absolute Deviation (LAD) Estimation and M-estimation and also to find out the factors that affect the Gross Regional Domestic Product (GRDP) in West Java Province in 2021 based on the model resulting from. Selection of the best model is seen based on the value of the coefficient of determination (R2) and Mean Squared of Error (MSE). The research results show that the Robust Geographically Weighted Regression (RGWR) method with M-estimation is much more effective in estimating the distribution of GRDP in West Java Province in 2021, seen from the larger coefficient of determination and the smaller Mean Square Error (MSE). The variables that have a significant influence on GRDP in West Java Province in 2021 are the variables of foreign investment and local income.

Green determination of glucocorticoids in water environment based on novel polydopamine coated iron tetroxide via magnetic dispersive solid phase microextraction

As the potential risks on human and aquatic animal exposed to the glucocorticoids in environment, it is essential to detect anti-epidemic pharmaceutical in real water samples. In this work, a core-shell shape, magnetic suspension particle sorbents of Fe3O4@oleic acid@polydopamine (Fe3O4@OA@PDA) were synthesized for magnetic dispersive solid phase microextraction (MDSPME), which possessed considerable dispersibility in water samples and extracted three glucocorticoids through hydrogen bonding with high detection sensitivity. The adsorption process of MDSPME was investigated by thermodynamic and kinetic theory, which demonstrated that the kinetic processes of adsorption were in accordance with the quasi second order kinetic model, and the adsorption isotherm was in accordance with the Freundich model. Combined with high performance liquid chromatography-Ultraviolet spectrophotometer detector, the proposed method had a linear range of 5–200 μg/L with an ultra-low detection limit down to 0.5–1.1 μg/L. The Green Analytical Greenness Metric (AGREE) software was employed to evaluate the greenness of the analytical method. This work presented an effective strategy for creating ultrasensitive and cost-effective probe for detection in anti-epidemic drugs.

Significant increases in detection capability for assessment of organic anion transporting polypeptide-mediated drug-drug interaction in cynomolgus monkeys by modifying pretreatment of Coproporphyrin I and III, and glycochenodeoxycholate-3-sulfate in plasma

BackgroundCoproporphyrin I (CP-I), Coproporphyrin III (CP-III), and glycochenodeoxycholate-3-sulfate (GCDCA-S) act as endogenous substrates of Organic Anion Transporting Polypeptide (OATP) 1B and have been considered for application in OATP1B-mediated drug‒drug interaction (DDI) risk assessments. Prior assays of the endogenous OATP substrates might exhibit reduced DDI detection capability and possibly overlook low DDI risk. We pioneered a simultaneous assay of the three substrates in monkey plasma using ultra-performance liquid chromatography with tandem mass spectrometry (UPLC-MS/MS) and applied it to monkey studies to identify lower DDI risk. ResultsThe methodology development indicated that precursors of CP-I/III were oxidized to form CP-I/III, diminishing the detection capability in DDI risk assessments. A precursor-eliminated analytical (PEA) method was developed to eliminate the precursors through solid-phase extraction. This method aimed to prevent the oxidation of CP-I/III precursors by incorporating edaravone. For comparison, a precursor-oxidized analytical (POA) method was also developed, wherein the precursors of CP-I/III were fully oxidized to CP-I/III. The PEA method achieved high sensitivity for CP-I/III and GCDCA-S, with lower quantification limits of 0.01 ng mL-1 and 0.5 ng mL-1, respectively. Both methods ensured that the validation parameters met the acceptance criteria. The two methods were applied to a monkey study, with CP-I/III showcasing notably enhanced DDI detection capabilities through the novel PEA method in comparison to the POA method. SignificanceThis study’s methodology has future implications for OATP-mediated DDI risk assessment using endogenous substrates. The novel PEA method can identify lower OATP-mediated DDI risks for drugs that the current methods cannot detect. Our method is likely applicable in clinical settings, and its utility should be assessed in clinical trials.

Wild raccoons demonstrate flexibility and individuality in innovative problem-solving.

Cognitive skills, such as innovative problem-solving, are hypothesized to aid animals in urban environments. However, the significance of innovation in wild populations, and its expression across individuals and socio-ecological conditions, is poorly understood. To identify how and when innovation arises in urban-dwelling species, we used advanced technologies and new testing and analytical methods to evaluate innovative problem-solving abilities of wild raccoons (Procyon lotor). We deployed multi-compartment puzzle boxes with either one or multiple solution types and identified raccoons using radio frequency identification. Raccoons solved these novel extractive foraging tasks, and their success was influenced by age and exploratory diversity. Successful raccoons always discovered multiple different solution types, highlighting flexible problem-solving. Using a unique, comparative sequence analysis approach, we found that variation in raccoon solving techniques was greater between individuals than within individuals, and this self-similarity intensified during times of competition. Finally, the inclusion of an easier solution in the multi-solution trials enabled previously unsuccessful raccoons to bootstrap their learning and successfully open multiple difficult solutions. Our study suggests that innovative problem-solving is probably influenced by many factors and has provided novel field and analytical methods, as well as new insights on the socio-ecological dynamics of urban populations.

Assessing spatial distribution of bioindicator elements in various cutaneous tumors using correlative imaging with laser-ablation-based analytical methods

Correlative imaging of cutaneous tumors provides additional information to the standard histopathologic examination. However, the joint progress in the establishment of analytical techniques, such as Laser-Induced Breakdown Spectroscopy (LIBS) and Laser Ablation Inductively Coupled Plasma Mass Spectrometry (LA-ICP-MS) in clinical practice is still limited. Their combination provides complementary information as it is also shown in our study in terms of major biotic (Ca, Mg, and P) and trace (Cu and Zn) elements. To elucidate changes in the elemental composition in tumors, we have compiled a set of malignant tumors (Squamous Cell Carcinoma, Basal Cell Carcinoma, Malignant Melanoma, and Epithelioid Angiosarcoma), one benign tumor (Pigmented Nevus) and one healthy-skin sample. The data processing was based on a methodological pipeline involving binary image registration and affine transformation. Thus, our paper brings a feasibility study of a practical methodological concept that enables us to compare LIBS and LA-ICP-MS results despite the mutual spatial distortion of original elemental images. Moreover, we also show that LIBS could be a sufficient pre-screening method even for a larger number of samples according to the speed and reproducibility of the analyses. Whereas LA-ICP-MS could serve as a ground truth and reference technique for preselected samples.

Berberine Contents as a Quality Marker in Medicinal Plants and Amounts of Berberine Passing into Serum

Background: Berberine is an alkaloid found in some medicinal plants. Berberine-containing plants have traditionally been used in the treatment of diseases since ancient times. Berberine is a natural compound that has an important place in traditional Chinese medicine. Currently, berberine is being evaluated extensively in clinical trials and is one of the natural products on which most scientific research studies have been published. Numerous clinical and pharmacological research results have been published on the therapeutic effect of berberine against cancer, diabetes, and heart disease Objective: The first purpose of this review is to display the berberine content of plants found in different regions of the world, and the second purpose is to provide the amount of berberine passing into the serum. Methods: Herbal supplements and extracts prepared from plants containing berberine are commercially marketed. The content of berberine in plants varies widely, and berberine is a quality indicator for many medicinal plants. Results: Different analytical methods have been developed for reliable berberine analysis. Plant and serum berberine levels reported between the years 2013 and 2022 in journals covered by SCI are collected in this review article. Conclusion: We hope that this overview of berberine amounts will be useful in future pharmaceutical and pharmacokinetic studies.

Analytical Characterization for Similarity Assessment Between an Aflibercept Biosimilar SB15 and Reference Product (Eylea®).

SB15 is a proposed biosimilar product of reference aflibercept (Eylea®), an approved biological drug product for retinal diseases including neovascular age-related macular degeneration (nAMD). This study aimed to assess the analytical similarity between SB15 and its commercially available reference product (RP) sourced from the United States (US-aflibercept) and European Union (EU-aflibercept) in terms of structural, physicochemical, and biological properties. A panel of state-of-the-art analytical methods was used for the comprehensive characterization of SB15 and US/EU-aflibercept. In terms of the structural and physicochemical properties, primary structure; post-translational modifications (PTM); higher-order structure; purity and impurities; charge variants; and glycosylation were compared. In addition, biological characterization including mechanism of action (MoA)-related and Fc-related biological activities was conducted. Analytical similarity between SB15 and US/EU-aflibercept was demonstrated. The primary and higher-order structure of SB15 was confirmed to be comparable to that of US/EU-aflibercept. In addition, there were no meaningful differences in the physicochemical properties in terms of size and charge heterogeneity between SB15 and its RP. SB15 and RP were similar in biological activities including MoA-related binding activities, potencies, and Fc-related biological functions. Consequently, SB15 was confirmed to be highly similar to US/EU-aflibercept. Based on a comprehensive analytical similarity assessment of structural, physicochemical, and biological properties, SB15 was demonstrated to be highly similar to US/EU-aflibercept RP, supporting safe and effective use of SB15.

State Estimation of Switched Time-Delay Complex Networks With Strict Decreasing LKF.

State estimation issue is investigated for a switched complex network (CN) with time delay and external disturbances. The considered model is general with a one-sided Lipschitz (OSL) nonlinear term, which is less conservative than Lipschitz one and has wide applications. Adaptive mode-dependent nonidentical event-triggered control (ETC) mechanisms for only partial nodes are proposed for state estimators, which are not only more practical and flexible but also reduce the conservatism of the results. By using dwell-time (DT) segmentation and convex combination methods, a novel discretized Lyapunov-Krasovskii functional (LKF) is developed such that the value of LKF at switching instants is strict monotone decreasing, which makes it easy for nonweighted L2 -gain analysis without additional conservative transformation. The main results are given in the form of linear matrix inequalities (LMIs), by which the control gains of the state estimator are designed. A numerical example is given to illustrate the advantages of the novel analytical method.

Precipitation of the gamma prime phase in a Ni-co-based superalloy during different stages of cooling

The cooling precipitation of the gamma primary (γ') phase in a precipitation strengthened Ni-Co-base disk superalloy was investigated by various experimental and analytical methods. The alloy was super-solvus heat treated and then slow cooled to different interrupted temperatures (IT) followed by instant water quenching. It shows that with the IT change, the γ' phase precipitated in different characteristics, such as morphologies, sizes and distributions. Through using three-dimensional atomic probe (3DAP) technique to study the γ and γ' compositions and their interface composition profiles, three types of γ' precipitates, entitled as quenching γ', primary cooling γ' and secondary cooling γ', were identified and their respective precipitation conditions and mechanisms were also discussed. According to the composition gradient across the γ/γ' interfaces and the γ' composition features, the separation mode of these γ' was determined to via the classical nucleation and growth mechanism. In addition, the effects of the γ' forming elements on the nucleation and growth processes of the different generations of γ' were evaluated. It indicates that the diffusion of Ti dominated the primary nucleation while that of Al reigned the following growth and the secondary nucleation.

Improving the food safety of bakery products by simultaneously monitoring the occurrence of pyrrolizidine, tropane and opium alkaloids

The exponential number of food alerts about concerning levels of some plant-alkaloids, such as pyrrolizidine, tropane and opium alkaloids, have stressed the need to monitor their occurrence in foods to avoid toxic health effects derived from their intake. Therefore, analytical strategies to simultaneously monitor the occurrence of these alkaloids should be developed to ensure food safety an comply with regulations. Accordingly, this work proposes an efficient multicomponent analytical strategy for the simultaneous extraction of these alkaloids from commercial bakery products. The analytical method was validated and applied to the analysis of 15 samples, revealing that 100% of them contained at least one of the target alkaloids, in some cases exceeding the maximum limits legislated. Moreover, in two samples the 3 different alkaloid families were detected. These results confirm the importance of simultaneously monitoring these alkaloids in food and highlight also considering some opium alkaloids in current legislation.

Development of Uv-visible and Hplc Analytical Methods for Quantitative Analysis of Antiulcer Drugs in Dosage Forms

Precise measurement of active pharmaceutical ingredients (APIs) in dosage forms is crucial in the pharmaceutical business to guarantee the quality, effectiveness, and safety of the product. This research is focused on creating and confirming analytical techniques for accurately measuring the amount of antiulcer medicines in different types of medication. The measurement of antiulcer medicines in their respective formulations was carried out using two analytical techniques: UV-Visible spectroscopy and High-Performance Liquid Chromatography (HPLC). UV-Visible spectroscopy is a straightforward and cost-effective method that allows for quick examination. It is particularly useful for regular quality control applications. HPLC, in contrast, offers exceptional sensitivity, specificity, and precision, facilitating the isolation and measurement of many constituents in complex matrices. The technique development procedure included optimizing experimental parameters, including solvent systems, detection wavelengths, column types, mobile phase composition, and flow rates. The reliability and robustness of the suggested procedures were ensured by validation studies done in accordance with ICH recommendations. The adequacy of the procedures for their intended purpose was assessed by evaluating parameters such as linearity, precision, accuracy, specificity, and robustness. The UV-Visible and HPLC techniques that were developed showed exceptional linearity over the examined concentration range, with correlation values (R²) above 0.99. The precision experiments showed low relative standard deviations (RSDs), suggesting excellent repeatability and moderate accuracy. The accuracy checks demonstrated that the recovery values were within acceptable ranges, therefore verifying the dependability of the methodologies used for quantitative analysis.

Impacts of Unsteady MHD Hybrid Nanofluid over a Non-linear Stretchable Porous Sheet with Thermal Radiation and Gyrotatic Microorganisms

This study offers a numerical assessment of unsteady laminar flow, heat and mass transfer of conventional hybrid nanofluid considering activation energy which is noticed in chemical processes. Further, non linear radiation and bioconvection flow with first order slip is also accounted. Nanoparticles as Cu and Al2O3 in the base fluid H2O are included in this analysis. Similarity transformation is applied to the governing model equations to reduce dimensionless form and "bvp4c" a MATLAB solver, is applied to get numerical outputs of flow problem. Validation of numerical outcomes is done by an analytical approach optimal auxiliary function method (OAFM). This analysis reports better thermal characteristics when volume fractions 0.0 ≤ φ1 ≤ 0.5 and 0.0 ≤ φ2 ≤ 0.5 of both nanoparticles Cu and Al2O3 are enhanced. Results for present analysis are interpreted numerically and graphically for distinct enhanced values of dimensionless parameters and physical quantities. The high resistance offered by velocity slip (0 ≤ Sv1 ≤ 1.0) and Forchheimer parameter (0 ≤ Fr ≤ 10) cause a drop in velocity profiles. It is noticed that bioconvection Peclet number (0 ≤ Pe ≤ 0.7) leading to a drop (χ(η = 1) = 0.139972to χ(η = 1) = 0.0817063) in density distribution of motile microorganisms.

A Reduced-Order Impedance Model and Analytical Loop-Correction Stabilization Method for Electric Vehicle DC Charging Station

A Reduced-Order Impedance Model and Analytical Loop-Correction Stabilization Method for Electric Vehicle DC Charging Station

Extension of Analytical Solution Methods to the Stability of Exposed Stratified Cemented Backfills

Extension of Analytical Solution Methods to the Stability of Exposed Stratified Cemented Backfills

Cutting failure behavior of foam core sandwich plates

During the ship, collisions with reefs or grounding may cause damage to the hull of ships made of sandwich plates. The cutting failure mechanism of sandwich panels is still not fully understood. In this paper, the failure behavior of metal foam sandwich plates under cutting load by a wedge-shaped indenter is studied through analytical, experimental, and numerical methods. An analytical model is proposed to describe the cutting failure behavior of foam core sandwich plates. Based on experimental results, three distinct failure modes of foam sandwich plates with varying thicknesses are observed. Numerical simulations are performed, and analytical and numerical results capture experimental results reasonably. The effects of core thickness, face-sheet thickness, and tip angle and cutting angle of wedge indenter on the failure mode, load-carrying capacity and energy absorption performance of the sandwich plates are explored. The present analytical model can effectively predict the cutting failure behavior of sandwich plates.

Impact of internal standard selection on measurement results for long chain fatty acids in blood

IntroductionInternal standards correct for measurement variation due to sample loss. Isotope labeled analytes are ideal internal standards for the measurement of fatty acids in human plasma but are not always readily available. For this reason, quantification of multiple analytes at once is most often done using only a single or few internal standards. The magnitude of the impact this has on method accuracy and precision is not well studied for gas chromatography-mass spectrometry systems. ObjectiveThis study aims to estimate bias and changes in uncertainty associated with using alternative fatty acid isotopologue internal standards for the estimation of similar or dissimilar long chain fatty acids. MethodUsing a previously reported method for the quantification of 27 fatty acids in human plasma using 18 internal standards we obtained estimates of bias and uncertainty at up to three levels of fatty acid concentration. ResultsWith some notable exceptions, method accuracy remained relatively stable when using an alternative internal standard (Median Relative Absolute Percent Bias: 1.76%, Median Spike-Recovery Absolute Percent Bias: 8.82%), with larger changes in method precision (Median Increase in Variance: 141%). Additionally, the degree of difference between analyte and internal standard structure was related to the magnitude of bias and uncertainty of the measurement. ConclusionThe data presented here show that the choice of internal standard used to estimate fatty acid concentration can affect the accuracy and reliability of measurement results and, therefore, needs to be assessed carefully when developing analytical methods for the measurement of fatty acid profiles.Disclaimer: The findings and conclusions in this report are those of the author(s) and do not necessarily represent the official position of the Centers for Disease Control and Prevention/the Agency for Toxic Substances and Disease Registry. Use of trade names is for identification only and does not imply endorsement by the Centers for Disease Control and Prevention, the Public Health Service, and the US Department of Health and Human Services.

Application of ion chromatographic fingerprint analysis for quality evaluation of tobacco flavors

Tobacco flavor, an important tobacco additive, is an essential raw material in cigarette production that can effectively improve the quality of tobacco products, add aroma and taste, and increase the suction flavor. The quality consistency of tobacco flavors affects the quality stability of branded cigarettes. Therefore, the quality control of tobacco flavors is a major concern for cigarette and flavor manufacturers. Physical and chemical indices, odor similarity, and sensory efficacy are employed to evaluate the quality of tobacco flavors, and the analysis of chemical components in tobacco flavors is usually conducted using gas chromatography (GC) and high performance liquid chromatography (HPLC). However, because the composition of tobacco flavors is complex, their quality cannot be fully reflected using a single component or combination of components. Therefore, establishing an objective analytical method for the quality control of tobacco flavors is of extreme importance. Chromatographic fingerprint analysis is routinely used for the discriminative analysis of tobacco flavors. Chromatographic fingerprints refer to the general characteristics of the concentration profiles of different chemical compounds. In the daily procurement process, fingerprints established by GC and HPLC are effective for the evaluation and identification of tobacco flavors. However, given continuous improvements in aroma-imitation technology, some flavors with high similarity cannot be directly distinguished using existing methods. In this study, a method for the determination of organic acids and inorganic anions in tobacco flavors based on ion chromatography (IC) was developed to ensure the quality consistency of tobacco flavors. A 1.0 g sample of tobacco flavors and 10 mL of deionized water were mixed and vibrated for 30 min. The aqueous sample solution was passed through a 0.45 μm membrane filter and RP pretreatment column in succession to eliminate interferences and then subjected to IC. Standard solutions containing nine organic acids and seven inorganic anions were used to identify the anions in the tobacco flavors, and satisfactory reproducibility was obtained. The relative standard deviations (RSDs) for retention times and peak areas were <0.71% and <6.02%, respectively. The chromatographic fingerprints of four types of tobacco flavors (samples A-D) from five different batches were obtained. Nine tobacco flavor samples from different manufacturers (samples AY1-AY3, BY1-BY2, CY1-CY2, DY1-DY2) were also analyzed to obtain their chromatographic fingerprints. Hierarchical cluster and similarity analyses were used to evaluate the quality of tobacco flavors from different manufacturers. Hierarchical clustering refers to the process of subdividing a group of samples into clusters that exhibit a high degree of intracluster similarity and intercluster dissimilarity. The dendrograms obtained using SPSS 12.0 indicated good quality consistency among the samples in different batches. Samples AY3, BY2, CY2, and DY1 clustered with the batches of standard tobacco flavors. Therefore, hierarchical cluster analysis can effectively distinguish the quality of products from different manufacturers. The Similarity Evaluation System for Chromatographic Fingerprint of Traditional Chinese Medicine (version 2.0) was used to evaluate the similarity between the standard tobacco flavors and products from different manufacturers. Among the samples analyzed, samples AY3, BY2, CY2, and DY1 showed the highest similarity values (>97.7%), which was consistent with the results of the hierarchical cluster analysis. This finding indicates that IC combined with chromatographic fingerprint analysis could accurately determine the quality of tobacco flavors. GC combined with ultrasonic-assisted liquid-liquid extraction was also used to analyze the tobacco flavors and verify the accuracy of the proposed method. Compared with GC coupled with ultrasonic-assisted liquid-liquid extraction, IC demonstrated more significant quality differences among certain tobacco flavors.

Simultaneous determination of 21 perfluorinated and polyfluoroalkyl substances in plant oils by ultra-high performance liquid chromatography-triple quadrupole mass spectrometry

Edible plant oils are a key component of the daily human diet, and the quality and safety of plant oils are related to human health. Perfluorinated and polyfluoroalkyl substances (PFASs) are pollutants that can contaminate plant oil through the processing of raw materials or exposure to materials containing these substances. Thus, establishing a sensitive and accurate analytical method for the determination of PFASs is critical for ensuring the safety of plant oils. In this study, a method based on acetonitrile extraction and solid phase extraction purification combined with ultra-high performance liquid chromatography-triple quadrupole mass spectrometry (UHPLC-MS/MS) was developed for the simultaneous determination of 21 PFASs, including perfluorocarboxylic acids, perfluoroalkyl sulfonic acids, and fluorotelomer sulfonic acids, in edible plant oils. The chromatographic conditions and MS parameters were optimized, and the influences of the extraction solvents and purification method were systematically studied. Plant oil samples were directly extracted with acetonitrile and purified using a weak anion-exchange (WAX) column. The 21 target PFASs were separated on a reversed-phase C18 chromatographic column and detected using a triple quadrupole mass spectrometer with an electrospray ionization source. The mass spectrometer was operated in negative-ion mode. The target compounds were analyzed in multiple reaction monitoring (MRM) mode and quantified using an internal standard method. The results demonstrated that the severe interference observed during the detection of PFASs in the co-extracted substances was completely eliminated after the extraction mixture was purified using a WAX column. The 21 target PFASs showed good linearity in their corresponding ranges, with correlation coefficients greater than 0.995. The limits of detection (LODs) and limits of quantification (LOQs) of the method were in the range of 0.004-0.015 and 0.015-0.050 μg/kg, respectively. The recoveries ranged from 95.6% to 115.8%, with relative standard deviations (RSDs) in the range of 0.3%-10.9% (n=9). The established method is characterized by simple sample pretreatment, good sensitivity, high immunity to interferences, and good stability, rendering it suitable for the rapid analysis and accurate determination of typical PFASs in edible plant oils.

A simple and efficient supramolecular solvent based liquid phase microextraction method for the preconcentration of nickel from dandelion tea samples before FAAS quantification, and the practicality and greenness assessment of developed method

A sensitive, accurate and practical analytical method (supramolecular solvent based liquid phase microextraction – flame atomic absorption spectrometry (SUPRAS-LPME-FAAS) was developed for the determination of nickel in dandelion tea samples. All influential parameters of SUPRAS-LPME were optimized to attain low detection/quantification limits using a univariate optimization approach. Under the optimum SUPRAS-LPME-FAAS conditions, dynamic range, limit of detection (LOD) and limit of quantification (LOQ) were found to be 25.86–497.64 µg/kg, 8.20 µg/kg and 27.35 µg/kg, respectively. The detection power of FAAS system was augmented as 28-fold with the help of SUPRAS-LPME method. Recovery experiments were performed for the evaluation of the accuracy and the applicability of the SUPRAS-LPME-FAAS method and percent recovery results for the spiked dandelion tea samples were calculated between 86.0 – 131.8 % via matrix matching calibration strategy. Additionally, the practicality and greenness evaluations for the SUPRAS-LPME-FAAS method were carried out using BAGI and AGREEprep software, respectively.

Development and validation of stability indicating HPLC-DAD assay of adapalene, methylparaben and propylparaben in a cosmeceutical gel matrix with blueness, greenness and whiteness assessment via relative ranking: An ab initio-sub finem juxtaposed non-traditional approaches

Adapalene (ADA) is primarily used as a cosmeceutical gel in the treatment of mild-moderate acne and is also used off-label to treat keratosis pilaris as well as other skin conditions. A stability-indicating fit-for-purpose (FFP) method has been developed for co-determination of ADA, methylparaben (MPN), and propylparaben (PPN) combined in a cosmeceutical gel dosage form. This method was based on a reversed-phase RP-HPLC separation of the cited analytes. It avoided the use of tetrahydrofuran (THF), which is commonly used by both compendial and published procedures for determination of ADA, thus improving method blueness (applicability), greenness and whiteness. The method development and validation followed non-traditional eco-friendly approaches including chemical simulations and empirical modelling. The HPLC separation was performed on an RP Zorbax Eclipse XDB-C8 analytical column [150 × 4.6 mm, 5 µm (80 Å)] with gradient elution system of HPLC grade acetonitrile and 50 mM aqueous sodium dihydrogen phosphate buffer containing 5 mM ethylenediaminetetraacetic acid (EDTA) adjusted to pH 8.0 as the mobile phase at a flow rate of 2.5 mL min−1 and column oven was set at 25 °C. EDTA played an important role for reproducibility of retention time of the three analytes especially for ADA. It controlled control deprotonation of the three acidic analytes under study and hence reproduce their ionization, hydrophobicity, and hence retention time. Quantitation was achieved with the photodiode array detection (DAD) at wavelengths of 258 nm for both MPN and PPN and 312 nm for ADA. Target Measurement Uncertainty (TMU) for the three analytes was determined via two approaches; misclassification rates approach employing 100,000 Monte Carlo simulations (MCS) and in-specification probability (ISP) to ascertain fitness-for-purpose of the proposed method. Microsoft Excel workbooks were developed for both TMU calculation approaches in addition to calculation of procedure capability index (Ppk) and sigma level for each analyte and attached in the Supplementary material. Moreover, linearity of the method underwent additional assessment using the previously mentioned TMU and procedure capability determination techniques. The robustness of the method was checked using Plackett-Burman experimental design (PBD) as an empirical modelling technique which was examined thoroughly to detect some interactions. The calibration graphs for each drug were rectilinear in the range of 0.34–7.08, 0.38–7.00 and 0.08–1.75 µg mL−1 for ADA, MPN, and PPN, respectively. The stress testing revealed photostability of the three components and variable degrees of degradation in the other conditions. The proposed HPLC-DAD method was successfully validated and applied for the determination of the investigated analytes in a gel matrix. In addition, method blueness and greenness were comparatively evaluated via very recent approaches of Blue Applicability Grade Index (BAGI), Green Solvents Selection Tool (GSST), Spider Diagram for Assessment of the Green Analytical Index (SDAGI), Analytical Method Greenness Score (AMGS), Carbon Footprint (CF), Modified Complementary Green Analytical Procedure Index (ComplexMoGAPI), and Analytical GREEnness Metric Approach (AGREE). Furthermore, the method whiteness was assessed via Red Green Blue Twelve (RGB 12) model following a relative ranking approach.