Micellar Electrokinetic Chromatography Research Articles

Pioneering simultaneous determination of breast cancer medications and metformin through sustainable micellar electrokinetic chromatographic method

The current study is the first report for the capillary electrophoretic simultaneous determination of five breast cancer medications, including febuxostat, quercetin, letrozole and doxorubicin in addition to metformin which is frequently co-administered with these drugs. The studied drugs are frequently purchased in different co-formulations used for breast cancer patients. A green micellar electrokinetic chromatographic (MEKC) method is proposed and optimized assisted by factorial design. The factors optimized include pH and concentration of buffer, surfactant concentration, as well as the applied voltage and injection time. The experimental results prove the optimum separation of the five drugs at pH 9.7 and buffer concentration of 10 mM with sodium dodecyl sulfate (SDS) concentration of 40 mM with +25 kV applied voltage. The developed method is validated considering linearity, precision, accuracy, and robustness adopting official guidelines. Good linearity is observed for all drugs, with correlation coefficients greater than 0.99. The range of percentage recoveries was from 98% to 102% with less than 2% relative standard deviation demonstrating the precision and accuracy of the established method. The study includes in-vitro assay of febuxostat, metformin, and doxorubicin in spiked human plasma. In addition, Accurate determination of the analytes under study in a variety of pharmaceutical dosage forms is accomplished by application of the proposed MEKC method. The greenness profile of the investigated method is confirmed using analytical eco-scale in addition to green analytical procedure index (GAPI) approaches.

Simple simultaneous analysis of various cardiovascular drug mixtures with vincamine: comparative eco-friendly assessment

The development of two eco-friendly analytical methods for the simultaneous determination of eight cardiovascular drugs; hydrochlorothiazide (HCT), captopril (CPL), lisinopril (LSP), valsartan (VAL), atorvastatin (ATR), bisoprolol (BSL), amlodipine (AML) and carvedilol (CVL); alongside with the nutraceutical vincamine (VIC) is essential for sustainable pharmaceutical analysis. This study explores the application of Micellar Electro Kinetic Chromatography (MEKC) and High-Performance Liquid Chromatography (HPLC) for this purpose. In MEKC method, the separation was done using fused silica capillary (41.5 cm × 50 µm id) and a back ground electrolyte consisting of 50 mM borate buffer (pH 9) containing 50 mM sodium lauryl sulphate (SLS) and 10% organic modifier (Acetonitrile). In HPLC method, separation was performed on a ZORBAX Extend-C18 (4.6 × 250 mm, 5 µm) column, using a gradient mobile phase consisting of 50 mM phosphate buffer pH 3 and methanol. Both methods attained good linearity (r ≥ 0.9996) with low values of LOD and LOQ. Both methods were successfully applied in the determination of co-administered single, binary and ternary dosage form of the studied drugs. Moreover, application of various combinations of co-administered dosage forms was achieved in rat plasma, confirming the applicability of these methods in different matrices. The use of micellar solutions in MEKC enhances separation efficiency while reducing the need for organic solvents, aligning with green chemistry principles. HPLC methods were optimized using environmentally benign solvents, ensuring reduced toxicity and waste production. The methodologies were evaluated through green, white, and blue metrics to ensure comprehensive sustainability, considering ecological impact, safety, and practical efficiency. These methods were not only cost-effective and time-saving but achieved high efficiency, sensitivity, and reproducibility making them ideal for routine use in pharmaceutical analysis.

Выбор рационального инструментария для анализа полифенолов цветков бессмертника песчаного и листьев артишока колючего в комплексе фармакологических исследований

Background: Pathology of the hepatobiliary system includes a heterogeneous group of diseases of the liver and biliary system caused by viral, bacterial and parasitic infections, neoplasms, toxic chemicals, including alcohol, nutritional errors, metabolic disorders and heart failure. One of the basic groups for pharmacological correction of this group of diseases is the use of hepatoprotectors, drugs that have a predominantly selective effect on the liver. The active ingredient of most plant hepatoprotectors are flavonoids and hydroxycinnamic acids. The most popular plants – hepatoprotectors containing these active substances include – artichoke prickly (Cynara scolymus (L.)) and sandy everlasting (Helichrysum arenarium (L.) Moench), a plant with choleretic action, also capable of hepatoprotective activity. The aim of the study: Development and comparative characterisation of methods for the analysis of polyphenolic composition of sandy everlasting flowers and artichoke leaves in complex pharmacological studies using HPLC and capillary electrophoresis methods. Materials and methods: The sum of polyphenolic compounds was subjected to chromatographic separation in gradient elution mode. Capillary electrophoresis was carried out in a variant of micellar electrokinetic chromatography (MEKC). The buffer solution used was a mixture of: borate buffer 20 mM (pH - 9.3) – beta-cyclodextrin 20 mM – ethyl alcohol (10:10:5). Results: The electrophoregrams of the separation of artichoke leaf extract by the MECC method showed the presence of 7 components belonging to oxycinnamic acids and flavonoids. The dominant ones are chlorogenic acid and luteolin7-glucoside. Similar results were obtained by the HPLC method. The electrophoregram of immortelle flower extract shows 9 components, of which the dominant one belongs to isosalipurposide. Chromatographic analysis of sandy everlasting flower extract showed the presence of the same components. Conclusion: The results of the analysis of the polyphenolic complex of artichoke leaves and sandy everlasting flowers by capillary electrophoresis agree with the data obtained by HPLC chromatography. This allows us to conclude that the MECC method allows the identification and quantification of each component in artichoke leaves and HPLC chromatography flowers along with HPLC. Moreover, the performance of the analysis by CE is more economically feasible than HPLC, since it does not require the use of solvents for the mobile phase and the availability of a set of columns.

Determination of caffeine by micellar electrokinetic chromatography in different beverages

Determination of caffeine by micellar electrokinetic chromatography in different beverages

Analysis of doxorubicin and fullerenol in rat serum by micellar electrokinetic capillary chromatography.

A new micellar electrokinetic capillary chromatographic (MEKC) method has been developed and optimized for simultaneous quantitation of doxorubicin (Dox) and fullerenol (Frl) in rat serum. The separation was carried out in a capillary (48.5-40 cm to the detector - 50 µm id fused-silica capillary with bubble cell, 150 µm) at an applied voltage of 25 kV and temperature of 25 °C. For the background electrolyte 10 mmol L- 1 borate buffer pH 9.3 plus 15 mmol L-1 phosphate buffer pH 7.0 (with the final pH of the mixture adjusted to 7.0 with HCl), with added 10 % (V/V) methanol, and 15 mmol L-1 sodium dodecyl sulfate as a surfactant, were used. The hydrodynamic injection was carried out at 5.0 kPa during the period of 100 s. Linear calibration curves were established over the concentration range 0.5-500.0 mg L- 1 for Dox and 10.0-500.0 mg L- 1 for Frl (at 234 nm). The proposed MEKC procedure was fully validated and applied for the deter mination of Dox and Frl in Wistar rats after intra pe ritoneal administration of both molecules.

Antimalarial analysis of pharmaceutical formulations and biological samples by capillary electrophoresis: the state of the art and applications.

Malaria is a serious public health problem, being an endemic disease in 84 countries, mainly in Africa. This review explores the application of capillary electrophoresis (CE) techniques for analyzing antimalarial drugs, highlighting methods from 2000 to 2023 for the analysis of pharmaceutical formulations and human biological samples. The versatility, selectivity, high efficiency, cost-effectiveness, and high analytical frequency of CE techniques have become attractive choices for pharmaceutical analysis, focusing on quality control and impurity analysis applications. The evolution of achiral and chiral electromigration methods has been described based on the features of each mode of separation: capillary zone electrophoresis (CZE), micellar electrokinetic chromatography, microemulsion electrokinetic chromatography, and capillary electrochromatography. As expected, CZE is reported in most articles owing to its compatibility with drug properties and separation mode. However, it is necessary to perform other separation modes for a few drugs that are present in neutral form. After exhaustive research using different databases and statistical analyses, 27 articles using CE techniques for antimalarial drug analysis were found and are mentioned in this review.

On-Line Preconcentration and Determination of Nuciferine and O-Nornuciferine in Lotus Leaves by Cation-Selective Exhaustive Injection (CSEI)-Sweeping-Micellar Electrokinetic Chromatography (MEKC)

On-line preconcentration incorporating cation-selective exhaustive injection (CSEI) and sweeping followed by micellar electrokinetic chromatography (MEKC) was developed for the simultaneous determination of the bioactive alkaloids nuciferine and O-nornuciferine. The parameters affecting the analytical performance were systematically investigated. Under the optimal conditions, the enrichment factor was significantly improved by 7000 to 13000-fold compared with traditional MEKC. The analytes were well separated within 15 min. The limits of detection for nuciferine and O-nornuciferine were 4.00 and 2.00 ng∙mL−1, and the limits of quantification were 8.00 and 10.00 ng∙mL−1, respectively. The relative standard deviations for intra-day and inter-day precision were less than 3.0%. The recoveries of the analytes were from 98.9% to 102%. Furthermore, the developed method was demonstrated to be suitable for the analysis of nuciferine and O-nornuciferine in lotus leaves, offering high performance without the loss of resolution. CSEI-sweeping-MEKC provides a simple, environmental-friendly option for preconcentration and quantification of nuciferine and O-nornuciferine.

Analytical quality by design-based development of a capillary electrophoresis method for Omeprazole impurity profiling

Omeprazole (OME) is a proton pump inhibitor used to treat gastroesophageal reflux disease associated conditions. The current study presents an Analytical Quality by Design-based approach for the development of a CE method for OME impurity profiling. The scouting experiments suggested the selection of solvent modified Micellar ElectroKinetic Chromatography operative mode using a pseudostationary phase composed of sodium dodecyl sulfate (SDS) micelles and n-butanol as organic modifier in borate buffer. A symmetric three-level screening matrix 37//16 was used to evaluate the effect of Critical Method Parameters, including Background Electrolyte composition and instrumental settings, on Critical Method Attributes (critical resolution values, OME peak width and analysis time). The analytical procedure was optimized using Response Surface Methodology through a Central Composite Orthogonal Design. Risk of failure maps made it possible to define the Method Operable Design Region, within which the following optimized conditions were selected: 72 mM borate buffer pH 10.0, 96 mM SDS, 1.45 %v/v n-butanol, capillary temperature 21 °C, applied voltage 25 kV. The method was validated according to ICH guidelines and robustness was evaluated using a Plackett-Burman design. The developed procedure enables the simultaneous determination of OME and seven related impurities, and has been successfully applied to the analysis of pharmaceutical formulations.

Comparison of aqueous and non-aqueous capillary electrophoresis for the determination of four benzalkonium chloride homologues in compound chemical disinfectants

A new method was established for the simultaneous analysis of four homologous benzalkonium chlorides (dodecyldimethylbenzyl ammonium chloride, tetradecyldimethylbenzyl ammonium chloride, hexadecyldimethylbenzyl ammonium chloride, and octadecyldimethylbenzyl ammonium chloride) in compound chemical disinfectants using non-aqueous capillary electrophoresis (CE) based on a micellar electrokinetic chromatography mode with direct ultraviolet detection. The separation was performed on an uncoated fused quartz capillary with a total length of 60.2 cm and a diameter of 25 μm. The separation buffer consisted of a mixture of methanol/acetonitrile (60:40, v/v) containing 70 mmol/L sodium acetate, 60 mmol/L trifluoroacetic acid and 20 mmol/L sodium dodecyl sulfate. The sample buffer was a methanol solution containing only 2 mmol/L trifluoroacetic acid. The separation voltage was set at 8 kV with a working current of approximately 2.3 μA. The detection wavelength was 214 nm. Under optimal conditions, the limit of detection and limit of quantification for these four benzalkonium chlorides (BACs) were 1.0 mg/L and 5.0 mg/L, respectively. Good linearities were observed in the concentration ranges from 5.0 to 100.0 mg/L, with correlation coefficients above 0.999 for all compounds. The recoveries of these four BACs ranged from 92.5 % to 109.1 % with relative standard deviations below 4.7 %. With the new method, all four BACs could be analyzed in a single injection. In contrast, the aqueous CE method in the National Standard GB/T 26369-2020 only allowed for the simultaneous analysis of the first three homologous. The new method demonstrated the improved peak shape compared to the aqueous CE method and then was successfully applied to the analysis of 19 commercially available samples, such as object table disinfectants, hand sanitizers, and disinfectant wipes, which claimed to contain quaternary ammonium compound. The results obtained using the new method were compared with those of the aqueous CE of the National Standard Method, and no statistically significant differences were observed. The new method is simple in pre-treatment and provides accurate results, making it highly suitable for routine analysis.

Multi-criteria decision analysis: technique for order of preference by similarity to ideal solution for selecting greener analytical method in the determination of mifepristone in environmental water samples

This work proposes the use of multi-criteria decision analysis (MCDA) to select a more environmentally friendly analytical procedure. TOPSIS, which stands for Technique for Order of Preference by Similarity to Ideal Solution, is an example of a MCDA method that may be used to rank or select best alternative based on various criteria. Thirteen analytical procedures were used in this study as TOPSIS input choices for mifepristone determination in water samples. The input data, which consisted of these choices, was described using assessment criteria based on 12 principles of green analytical chemistry (GAC). Based on the objective mean weighting (MW), the weights for each criterion were assigned equally. The most preferred analytical method according to the ranking was solid phase extraction with micellar electrokinetic chromatography (SPE-MEKC), while solid phase extraction combined with ultra-high performance liquid chromatography tandem mass spectrometry (SPE-UHPLC-MS/MS) was ranked last. TOPSIS ranking results were also compared to the green metrics NEMI, Eco-Scale, GAPI, AGREE, and AGREEprep that were used to assess the greenness of thirteen analytical methods for mifepristone determination. The results demonstrated that only the AGREE metric tool correlated with TOPSIS; however, there was no correlation with other metric tools. The analysis results suggest that TOPSIS is a very useful tool for ranking or selecting the analytical procedure in terms of its greenness and that it can be easily integrated with other green metrics tools for method greenness assessment.

Simultaneous separation and determination of seven biphenyl cyclooctene lignans in Schisandra chinensis and its preparations by micellar electrokinetic chromatography with dual organic solvent system.

Gomisin is a natural dibenzo cyclooctene lignan, which is mainly derived from the family Magnoliaceae. It has anti-inflammatory, antioxidant, anti-tumor, anti-aging, and hypoglycemic effects. Gomisins play important roles as medicines, nutraceuticals, food additives, and cosmetics. The objective of this study is to establish a micellar electrokinetic chromatography (MEKC) method for simultaneous separation and determination of seven biphenyl cyclooctene lignans (Gomisin D, E, G, H, J, N, and O) in Schisandra chinensis and its preparations. The method was optimized by studying the effects of the main parameters on the separation. The method has been validated and successfully applied to the determination of seven Gomisins in S.chinensis and its preparations. In the separation system, the running buffer was composed of 20 mM Na2HPO4, 8.0 mM sodium dodecyl sulfate (SDS), 11% (v/v) methanol, and 6.0% (v/v) ethanol. A diode array detector was used with a detection wavelength of 230 nm, a separation voltage of 17 kV, and an operating temperature of 25°C. Under this condition, the seven analytes were separated at baseline within 20 min, and a good linear relationship was obtained with correlation coefficient ranging from 0.9919 to 0.9992. The limit of detection (LOD, S/N = 3) and the limit of quantification (LOQ, S/N = 10) ranged from 0.8 to 0.9μg/mL and from 2.6 to 3.0μg/mL, respectively. The recovery rate was between 99.1% and 102.5%. The experimental results indicated that this method is suitable for the separation and determination of seven Schisandra biphenyl cyclooctene lignan compounds in real samples. At the same time, it provides an effective reference for the quality control of S.chinensis and its preparations.

Purines recognition and quantitative analysis by surface-enhanced Raman spectroscopy

The common quantification methods of purines, including high-performance liquid chromatography, micellar electrokinetic chromatography, reverse phase ion pair chromatography, and capillary zone electrophoresis, have been used for the analysis of purines. These conventional techniques are limited by long operation times, large sample volumes, requirements for pretreatment and separation processes, or sophisticated, bulky and expensive equipment. Here, we have developed a simple method to prepare a probe for the quantitative analysis of purines using the surface-enhanced Raman scattering (SERS) method. The SERS probe is a rough Ag wire obtained with simple electrochemical treatment, which is optimized to reach the maximum SERS signal enhancement. The Raman enhancement factor (EF) of Ag wire after roughening can reach ∼106. Under optimized conditions, the rough Ag wire is capable of recognizing four purine bases (namely, guanine, adenine, hypoxanthine, and xanthine) in the range of 10−5 to 10−1 mg/mL with a linear relationship between SERS intensity of signature peak and purine concentration. The recovery rate of each purine base is higher than 80% in the mixture of four purines. The overall method was successfully applied to the monitoring of the level of purines in marketplace beer beverages. The novel wire-based SERS sensor used with portable Raman spectroscopy is prospective in diet safety and personalized point-of-care medical detection.

Rapid indirect separation of glutamine enantiomers by micellar electrokinetic chromatography. Analysis of dietary supplements.

Glutamine is the most abundant free proteinogenic α-amino acid. It is naturally produced in the organism and acts as a precursor for the synthesis of different biologically important molecules (such as proteins or nucleotides). However, under stressful conditions, the organism is unable to produce it in enough amounts to function properly. Thus, glutamine (Gln)-based supplements have become increasingly popular over the last decade. Since legal regulations establish that amino acid-based dietary supplements must contain only the L-enantiomer and not the racemate, adequate chiral methodologies are required to achieve their quality control. In this work, an analytical methodology based on the use of micellar electrokinetic chromatography is proposed for the rapid enantiomeric determination of DL-Gln in dietary supplements. Using (+)-1-(9-fluorenyl)-ethyl chloroformate as a derivatizing agent and ammonium perfluorooctanoate as separation medium, the Gln diastereoisomers formed under optimal conditions were separated in 8min with a resolution of 2.8. The analytical characteristics of the method were evaluated in terms of linearity, precision, accuracy, and limits of detection/quantitation, and they were found appropriate for the analysis of L-Gln-based dietary supplements.

Abstract TP162: Polyamine Levels Are Elevated After Intracerebral Hemorrhage

Introduction: Intracerebral hemorrhage (ICH) has high morbidity and mortality without available targets for intervention. Polyamines are metabolites implicated in neurological diseases such as traumatic brain injury, Alzheimer’s Disease, and ischemic stroke. No studies have evaluated polyamines as they relate to ICH occurrence or outcomes. In this pilot study, we sought preliminary data on whether polyamines could be potential novel targets to improve outcomes after ICH. Methods: We analyzed plasma samples from 7 ICH cases and 10 control participants from the Genetics and Environmental Risk Factors for Stroke (GERFHS) IV study for polyamine measurements using Capillary Electrophoresis with Laser Induced Fluorescence Detection with the modality of Micellar Electrokinetic Chromatography. Plasma samples were deproteinized and derivatized with Fluorescein Isothiocyanate. Samples were spiked with standard solutions and compared with standard curves developed per each polyamine. We report median age and sex of the cohort. Peak spermine, spermidine and putrescine levels were compared using a student’s t-test. Results: In this pilot study of participants enrolled into GERFHS IV (median age 67 vs 61, cases vs controls respectively, 50% female) all three unacetylated polyamine levels were higher in cases. Although sample size is modest, there was a trend towards increased spermidine levels with higher mRS at 90 days (r 2 = 0.3342) (Figure 1). Conclusions: For the first time, we have shown that polyamines are elevated after ICH, and that higher polyamine levels may be associated with worse outcomes. This preliminary data supports further evaluation of polyamines as potential targets to improve outcomes after ICH in a larger cohort.

Capillary electrophoresis separations with deep eutectic solvents as greener separation media: A proof-of-concept study

Capillary electrophoresis (CE) has conventionally been classified into aqueous and non-aqueous categories based on the types of buffer solvents employed. Traditionally, non-aqueous CE has always been associated with the use of organic solvents, which are considered hazardous to health and environmentally detrimental. In this work, we introduce deep eutectic solvents (DESs) as CE separation media for the first time, presenting a novel and environmentally friendly approach to CE separations. The DES employed consists of proline and urea (Proline:Urea, PU), both of which are naturally occurring compounds that are readily available, cost-effective, and environmentally benign. Various fundamental aspects of the DES-type CE media were investigated, including thermal property, viscosity, electroconductivity, Joule heating effect, and compatibility with detectors. A simulated complex mixture of ten naphthalene-based compounds with varied charges and sizes was separated using the DES-based medium in capillary zone electrophoresis (CZE) mode. Moreover, we also established a DES-based micellar electrokinetic chromatography (MEKC) system utilizing Tween-20 as the surfactant. Six structurally similar naphthalene derivatives (isomers) that couldn't be resolved by CZE were effectively separated due to their strong hydrophobic interaction with Tween-20 micelles within the DES medium. Given that DESs are “designer” solvents with highly tunable properties and environmentally friendly characteristics, this study demonstrates the potential of employing DESs as an alternative to organic solvents for greener CE separations.

Comparative characteristics of different methods for electrophoretic determination of mono- and disaccarides using derivatization

The following variants of electrophoretic determination of sugars with prior derivatization are considered in the article: reductive amination using p-aminobenzoic acid ethyl ester (ABEE) and condensation with 1-phenyl-3-methyl-5-pyrazolone (PMP). Derivatization products were separated using capillary electrophoresis in both zone and micellar modes, and comparative estimate characteristics were obtained. The best efficiency (ca. 650 thousand theoretical plates), selectivity (2.1–2.4), and LOD (0.8–2.9 μg/mL) was observed for the separation of reductive amination products using micellar electrokinetic chromatography (MEKC). Optimization of derivatization conditions was performed for the reductive amination using the central composite experiment design. Additionally, LOD was lowered by the sample intracapillary concentration in sweeping mode, and sample enhancement factors (SEF) of 13–19 were achieved. A proof-of-concept possibility of the intracapillary reductive amination ensuring electrophoretic mobility of the derivatization reagent using detergent micelles as carrying agents was demonstrated. Both derivatization methods were applied for the analysis of baby food.

Determination of vitamins K1 and K3 in green tea and in pharmaceutical supplements by capillary micellar electrokinetic chromatography

A method based on capillary micellar electrokinetic chromatography (MEKC) was developed for vitamin K1 and K3 determination. Experimental and instrumental parameters optimized for electrophoretic separation with better peak efficiency were: borate buffer at 0.05 mol L−1, pH 8.5, cetyltrimethylammonium bromide (CTAB) at 0.05 mol L−1, acetonitrile 20 % v/v, 25 °C and a negative potential difference of 30 kV. Sample introduction was made by hydrodynamic at 50 mbar for 15 s. Migration times for vitamins K1 and K3 were (5.2 ± 0.1) and (3.4 ± 0.1) min respectively. Limits of detection and quantification were on the order of 10−5 g L−1 and 10−4 g L−1. For vitamin K1, the precision was between 2 and 7 % for the peak area. Recoveries were 101 ± 2 % and 103 ± 2 % for green tea and vitamin supplement samples, respectively. For vitamin K3, recoveries were 99 ± 3 % for vitamin supplement. Comparative tests were performed with the reference method based on liquid chromatography with agreement of results. The uncertainty and the contribution of the relevant sources was carefully evaluated. The method was found adequate to enable reliable and sensitive measurements of different forms of vitamin K with low consumption of solvents and less generation of waste.

On-line concentration and separation of multiple derivatized monosaccharides from edible fruit with cyclodextrin-encapsulated sweeping by micellar electrokinetic chromatography

An on-line enrichment and separation of multiple derivatized monosaccharides with cyclodextrin-encapsulated sweeping (CDES) by micellar electrokinetic chromatography (MEKC) was presented. Five monosaccharides (L-(−)-Mannose, D-(+)-Glucose, D-(−)-Ribose, D-(+)-Xylose, and L-(+)-Rhamnose) were derivatized with 1-phenyl-3-methyl-5-pyrazolone, subsequently concentrated and separated by MEKC. The optimized conditions were as follows: 50 mM phosphoric acid (PA), 100 mM sodium dodecyl sulfate (SDS), and 30 % (v/v) methanol in background solution; 140 s injection of sample solution containing 50 mM CD and 100 mM PA, followed by 90 s injection of 40 mM SDS solution. Under the optimized conditions, the correlation coefficients ≥ 0.9953, and the limits of detection ranged from 4.2 to 7.4 ng/mL. Relative standard deviation values ranged from 0.24–4.23 %, and sensitivity enrichment factors were in the range of 53–82 compared with typical injection (50 mbar, 3 s). The CDES-MEKC method was successfully applied to Jujube with good recoveries of 84.22–104.33 %. The method provides new ideas for the on-line enrichment and detection of trace monosaccharides and even other target analytes in foods with complex matrices.

Analytical Methods and Regulative Viewpoint of Antimicrobial Preservatives in Cosmetics

Cosmetics need to be resistant to microbial contamination to protect consumer health and increase shelf life, much like any other product containing water, organic and inorganic components. The aims of anti-microbiological activity are to protect consumers from potentially harmful bacteria and to preserve products subject to degradation. Chemical, physical, or physicochemical methods are used to ensure this. Organic acid preservatives, alcohols, formaldehyde releasers, halogenated preservatives, isothiazolinones, quaternary ammonium salts and chlorhexidine are among the preservatives included in the legislation. Indeed, high quantitiesare more successful from a preservation standpoint, nevertheless they are toxic to consumers, whereas low amounts can lead to microbial resistance. Accordingly, the criteria of several international legislation and validation methods for introducing microbiologically safe items to the market have become essential. Although there are many approaches based on gas chromatography (GC) as per literature, the most common methods for the determination of preservatives are based on liquid chromatography (LC). Both of these procedures, as well as capillary electrophoresis (CE) and micellar electro kinetic chromatography (MEKC), have been frequently utilized in the cosmetics industry to determine preservative levels. Analytical approaches have been primarily focused on parabens, whereas the number of available methods to investigate other preservatives is limited. There is a tendency toward the usage of miniature extraction processes where new and improved sample preparation and extraction techniques including matrix solid-phase dispersion, solid-phase extraction, pressurized liquid extraction/supercritical fluid extraction and microextraction-based method have been introduced with high levels of efficiency and extraction capacities. Considering the significance and relevance of preservatives in cosmetics, this study highlights the most recent state-of-the-art information on their safety and regulatory concerns. Given the rising influence on consumer health, sample preparation and analytical methods forpreservative detection were also investigated which have been proposed by the international scientific literature.
 Keywords: Preservatives, Cosmetics, Analytical Techniques, Derivatization, Extraction

A novel cation-selective exhaustive injection and sweeping micellar electrokinetic chromatography method for the simultaneous determination of second-generation triazoles in human plasma

In this study, we introduce the first capillary electrophoresis method that combines cation-selective exhaustive injection and sweeping micellar electrokinetic chromatography (CSEI-sweeping-MEKC) for the simultaneous and sensitive quantification of voriconazole (VRC), posaconazole (PSC), and isavuconazole (ISV) levels in human plasma. The sensitivity was remarkably improved, with a 5374-fold enhancement compared to the traditional MEKC method. We systematically optimized key parameters affecting sensitivity, resolution, and efficiency. The separation buffer included 100 mM NaH2PO4, 13 % acetonitrile, and 13 % tetrahydrofuran. This was followed by a high-conductivity buffer zone (1 psi, 50 s) of 100 mM NaH2PO4, an extended electrokinetic sample injection (10 kV, 600 s), and analyte sweeping with 100 mM sodium dodecyl sulfate micelles at −20 kV. Under these optimized conditions, the method allowed for an analytical run in 10 min and was validated for linearity (r ≥ 0.9997), precision (%RSD ≤ 8.8 %), and accuracy (%RE ≤ 2.20 %), delivering satisfactory results. The limit of detection was 2.55 ng/mL for ISV, 0.89 ng/mL for PSC, and 1.04 ng/mL for VRC. This method was successfully applied to analyze plasma samples from patients undergoing triazole antifungal treatment, demonstrating its feasibility for clinical testing.