Dispersive Liquid-liquid Microextraction Research Articles

Ionic liquids-based adsorbents for extraction and separation: A review emphasizing recent advances in sample preparation

Ionic liquids (ILs) exhibit remarkable physical and chemical properties, encompassing negligible vapor pressure, non-flammability, high thermal stability and mechanical robustness. Moreover, ILs can be readily tailored for specific functions by altering the combination of cations and anions. These unique attributes have led to the widespread adoption of ILs as highly efficient adsorbents in sample preparation. To meet the requirements of various applications, ILs are often immobilized or functionalized. This review summarizes the primary types of currently available ILs-based adsorbents, including poly(ionic liquids), ILs-modified silica-based adsorbents, ILs-modified carbon-based adsorbents, ILs@metal–organic frameworks composite adsorbents, and ILs@covalent organic frameworks composite adsorbents. Additionally, the applications of ILs-based adsorbents in sample preparation techniques such as dispersive liquid-liquid microextraction, single-drop microextraction, hollow fiber liquid-phase microextraction, solid-phase extraction, magnetic solid-phase extraction, and solid-phase microextraction are introduced. Furthermore, the review provides insights into the challenges and prospects for the future development of ILs-based adsorbents.

Effervescence-assisted dispersive liquid-liquid microextraction for the extraction and preconcentration of pesticide residues in fruit juice samples

BackgroundThe widespread use of pesticides for the protection of fruits has resulted in the presence of pesticide residue levels beyond their limit in fruits. This ensures their transfer to processed products, such as juices, posing a threat to human health. Therefore, an efficient and selective method is required for monitoring pesticide residues in fruit juices. Hence, an effervescence-assisted dispersive liquid-liquid microextraction based on solidification of floating organic droplets was developed for the simultaneous extraction of five pesticide residues of different classes. An environmentally green low-density organic solvent, 1-undecanol, was used as extraction solvent. (94) ResultsThe developed method was optimized and validated for quantitative extraction of multiclass pesticide residues at trace levels from fruit juice samples, including apple, pineapple, guava and orange samples. The method showed good linearity in the range of 0.8 to 300 ng mL-1 for all pesticide residues with a regression coefficient ranging from 0.9979 to 0.9997 under the optimized conditions. The LOD and LOQ of the method ranged between 0.03-0.16 ng mL-1 and 0.11-0.52 ng mL-1, respectively, indicating the high sensitivity of the proposed method. Repeatability and reproducibility, in terms of %RSD, were obtained in the range of 1.16-5.50% and 3.12-7.72%, respectively. (101) SignificanceThe developed method exhibited acceptable mean recoveries (%R) in the range of 73.77-113.34 % with %RSDs (n=3) ranging from 1.25 to 7.74% for all the analytes studied. Therefore, the developed method can be used as a selective, sensitive and efficient extraction method for the extraction of multiclass pesticides from fruit juice samples. (52)

Application of magnetic AlFu MOF nanocomposite for the extraction and preconcentration of some pesticides from different distillates

This research used a magnetic AlFu nano-metal-organic framework as an adsorbent for the first time. This approach extracts and preconcentrates eight pesticides from various distillates through a two-step process: magnetic dispersive micro solid phase extraction and dispersive liquid-liquid microextraction. Initially, the nanocomposite is dispersed into a sample solution containing the pesticides and Na2SO4. The target pesticides are then adsorbed onto the nanocomposite, which is subsequently isolated from the aqueous phase using an external magnetic field. Acetonitrile is used to elute the adsorbed analytes pesticides from the nanocomposite surface. The resulting acetonitrile extract, containing the concentrated pesticides, is then mixed with a tiny amount of another solvent and injected into a NaCl solution. Centrifugation allows the organic phase, enriched with the pesticides, to settle down. An aliquot of this organic layer is then analyzed using a gas chromatography-flame ionization detector. Optimization of the procedure led to favorable performance, including good extraction recovery of the pesticides (68–98 %), significant enrichment (enrichment factors of 340–489), a wide range of detectable concentrations (2.90–1400 µg L−1), and low detection (0.15–0.88 µg L−1) and quantification limits. (0.49–2.90 µg L−1)

Personalization of pharmacotherapy with sirolimus based on volumetric absorptive microsampling (VAMS) in pediatric renal transplant recipients-from LC-MS/MS method validation to clinical application.

The benefits of pharmacotherapy with sirolimus (SIR) in pediatric transplant recipients are well established. Traditionally, whole blood samples have been used to measure SIR concentrations. Volumetric Absorptive Microsampling (VAMS) is an alternative sampling strategy suitable for Therapeutic Drug Monitoring (TDM). In this study, we developed and validated two liquid chromatography-tandem mass spectrometry (LC-MS/MS) methods for determining SIR concentrations in whole blood (WB) and capillary whole blood samples collected using a VAMS-Mitra™ device. We used protein precipitation during WB sample preparation and dispersive liquid-liquid microextraction (DLLME) with methyl tert-butyl ether for VAMS sample preparation to optimise the analyte extraction process. The described validation protocols were cross-validated, confirming the equivalence of the whole-blood and VAMS-based methods. Furthermore, the developed methods were evaluated in two three-level rounds of an external proficiency-testing scheme. The analytical methods were successfully validated within the calibration range of SIR (0.5-60 ng/ml). The validation parameters met the European Medicines Agency (EMA) and the International Association of Therapeutic Drug Monitoring and Clinical Toxicology (IATDM&CT) acceptance criteria. No hematocrit (tested in the range of 24.3-64.1%), matrix, or carry-over effects were observed. Cross-validation confirmed the interchangeability between VAMS-LC-MS/MS and WB-LC-MS/MS methods. The developed methods were successfully implemented for SIR determination in 140 clinical samples (70 each of WB and VAMS) from pediatric renal transplant recipients, demonstrating their practicality and reliability. The VAMS-based method has been rigorously tested and is clinically equivalent to the reference WB-LC-MS/MS method. Additionally, clinical validation confirmed the utility of the presented methods for TDM of the SIR in the pediatric population after renal transplantation.

Determination of Hydroxylated Polyaromatic Hydrocarbons in Urine by Gas Chromatography–Mass Spectrometry Using Dispersive Liquid-Liquid Microextraction and Injector-Port Derivatization

Determination of Hydroxylated Polyaromatic Hydrocarbons in Urine by Gas Chromatography–Mass Spectrometry Using Dispersive Liquid-Liquid Microextraction and Injector-Port Derivatization

Application of deep eutectic solvent based dispersive liquid–liquid microextraction method followed by HPLC-DAD for quantification of selected neonicotinoid pesticides in vegetable oils

The use of deep eutectic solvents (DES) as alternative green solvents in various analytical chemistry fields has garnered attention of researchers globally. Therefore, this study presents environmentally friendly DES for extraction of selected neonicotinoids (acetamiprid, imidacloprid, thiacloprid and thiamethoxam) prior to their determination using high-performance liquid chromatography- diode array detector (HPLC-DAD). The DES mixture that resulted in the highest extraction recoveries of neonicotinoids (NEOs) was choline chloride with ethylene glycol (CCl:EG) and nuclear magnetic resonance and Fourier transform infrared confirmed the successful synthesized CCl:EG. Thereafter, the CCl:EG was applied in dispersive liquid–liquid microextraction (DLLME) for the preconcentration and extraction of acetamiprid, imidacloprid, thiacloprid and thiamethoxam. The optimum factors affecting extraction efficiency of the DES-DLLME procedure were 0.8 mL (DES volume), 4.5 min (extraction time), 0.5 mL (eluent volume), 7 pH and 75 s (eluent time). The optimized DES-DLLME achieved limit of detection (LOD) and quantification (LOD) range of 0.4–4.95 ng.µL−1 and 1.43–9.70 ng.µL−1 respectively. Additionally, the extraction method achieved good accuracy (79.0–119.6 %), preconcentration factors (39.3–118), interday (0.61–1.62 %) and intraday (0.1–0.98 %) precisions. The greenness assessment of the proposed DES-DLLME method using AGREE, NEMI and AES tools revealed that the method was green. Finally, the developed DES-DLLME method was applied to real vegetable oils and the concentrations were below detection limits.

Online Flow-Batch Dispersive Liquid-Liquid Microextraction System for ET AAS Determination of Molybdenum in Water and Complex Matrices

Online Flow-Batch Dispersive Liquid-Liquid Microextraction System for ET AAS Determination of Molybdenum in Water and Complex Matrices

Preparation of a New Hexafluorobutanol-Farnesol Based Supramolecular Solvent and Its Application in Microextraction of Sudan Dyes From Beverage and Water Samples.

In this work, a new supramolecular solvent (SUPRAS) was prepared for the first time using hexafluorobutanol (HFB) and farnesol (FO). FO acts as an amphiphile and HFB as a coacervation inducer and density regulator. The method of dispersive liquid-liquid microextraction followed by high-performance liquid chromatography, supported by a vortex technique, was established using the prepared SUPRAS for the determination of Sudan dyes in aqueous samples. The extraction parameters, including FO content, HFB content, vortex time, salt addition, and solution pH, were thoroughly investigated and optimized. Under the optimized conditions, the linearity range is 10-750ng/mL for Sudan I, and 10-1000ng/mL for Sudan III and Sudan IV, respectively. The limits of detection for Sudan dyes were in the range of 0.8-3.1ng/mL. The inter- and intra-day relative standard deviations for Sudan dyes were in the range of 1.3%-4.1% and 0.2%-2.6%, respectively. Finally, the proposed method was applied to the determination of Sudan dyes in beverage and river water samples with recoveries ranging from 93.9% to 122.1%. Compared to conventional techniques for the extraction of Sudan dyes in real samples, the proposed method is simpler, faster, and more environmentally friendly.

Preconcentration of Cinnamic Acid Derivatives in Traditional Chinese Medicines by an Effective Dispersive Liquid-Liquid Microextraction Based on a Hydrophobic Deep Eutectic Solvent.

A dispersive liquid-liquid microextraction based on hydrophobic deep eutectic solvent (hDES) was developed for the extraction and quantification of four cinnamic acid derivatives in traditional Chinese medicines coupled with high-performance liquid chromatography-ultraviolet detection. In this method, a hDES (tetrabutylammonium chloride-hexanoic acid, molar ratio of 1:2) was prepared as the extractant. It only took 15 s to handle multiple samples simultaneously by hand-assisted dispersion. The use of a narrow-bore tube reduced the amount of the hydrophobic extractant with easier recovery. The approach was influenced by several key parameters, including the composition and consumption of the DES, sample phase pH, salt amount, extraction time, and centrifugation time, all of which had been investigated and optimized. Moreover, the formation of the DES was characterized by Fourier-transform infrared spectroscopy and differential scanning calorimetry. Under the optimal conditions, enrichment factors of the target analytes ranged from 135 to 220. Satisfactory linearities (r ≥ 0.9977), detection limits (0.2-0.4ng/mL), precision (<8.5%), and accuracy (recoveries: 90.0%-104.6%) were obtained. The method has been successfully applied to the simultaneous extraction and preconcentration of four cinnamic acid derivatives in Chinese medicinal samples with rapidness, high efficiency, and convenience.

Design of a novel deep eutectic solvent for microextraction of Lissamine green B from food Samples: A green approach

The extraction of Lissamine Green B (LGB) from food matrices poses a challenge due to its low concentration and interference from other matrix compounds. In this study, a novel green approach utilizing a deep eutectic solvent (DES) for dispersive liquid microextraction (GDES- DLLME) of LGB is presented. The DES, formulated from eco-friendly components and synthesized through mechanochemical methods for the first time, presents a sustainable alternative to traditional solvents. The DES characterization was implemented via 1H and 13C Nuclear Magnetic Resonance spectroscopy (NMR) analysis. The microextraction procedure was optimized for maximum efficiency, considering factors such as extraction time, DES composition, and sample pH, THF volume, NaCl amount, sample volume etc. The developed method was then applied to various food samples using spectrophotometric detection for the quantitative analysis of LGB, including water samples, beverages and foods. Furthermore, analytical performance values such as limit of detection (LOD), limit of quantification (LOQ), relative standard deviation (RSD), and preconcentration factor (PF) were calculated as 0.76 ng/mL, 2.56 ng/mL, % 4.6, and 22.5 respectively. The results demonstrated the effectiveness of simply generated DES as an extraction solvent and enabled sensitive and selective determination of LGB in complex food matrices. This eco-friendly method is promising for food safety and quality control applications, providing a sustainable solution for the analysis of LGBs in food.

A Simple Dispersive Liquid-Liquid Microextraction for the Determination of Copper II in the Water Samples of the Halfaya Oil Field in Maysan

Background: Copper, an important trace element for life on Earth, is crucial to many metabolic processes. This includes its role in the production and breakdown of nucleic acids and the metabolism of proteins, lipids, and carbohydrates. Objective: We aim to integrate DLLME with a spectrophotometric method to establish a novel approach for quantifying trace amounts of copper in water samples. Methods: In this study, a new ligand known as a 2-(4 aminophenol) benzimidazole azo derivative was successfully synthesized. This ligand was created by converting 2-(4-aminophenyl) benzimidazole into a diazonium salt and coupling it with 8-hydroxyquinoline in an alkaline environment. The resulting product was a brown azo dye, which served as the ligand for detecting copper (II) in aqueous samples. Results: To analyze copper (II) in both pure and aqueous samples, we developed and validated micro-extraction techniques combined with UV-Vis measurement. Specifically, we used the DLLME (dispersive liquid-liquid microextraction) method to separate, enrich, and assess copper (II) in both its pure form and in aqueous samples. UV-Vis spectroscopy at a wavelength of 503 nm was used for this purpose. We considered several variables during the experiment, including the type and volume of the dispersive solvent, the extraction solvents, the temperature, the reaction duration, and the centrifuging time. By optimizing these conditions, we achieved linear procedures within the concentration range of (1.0–25.0) and (2.0–25.0) μg/mL for spectroscopy and DLLME methods, respectively. For the spectroscopic and DLLME approaches, the coefficient of determination (R2) was found to be 0.9963 and 0.9979 for the spectrophotometric and DLLME methods, respectively. The limit of detection (LOD) for copper (II) was found to be 0.23 and 0.04 μg/mL, respectively. Moreover, the recovery of the target analyte in aqueous samples was found to be between 95.6% and 101% for the spectroscopy method and between 102.4% and 108.2% for the DLLME method. Conclusions: These results demonstrate the effectiveness and accuracy of both methods in analyzing copper (II) in aqueous samples.

Development of a green microextraction procedure for determining polyaromatic hydrocarbons in electronic equipment plastics

The global proliferation of electronic devices, driven by technological advancements, has led to the release of organic pollutants from the plastic components of these devices, particularly in indoor environments. Among these pollutants, polycyclic aromatic hydrocarbons (PAHs), which are emitted into the air from plastic components, play a critical role in the field of indoor environment pollution. Consequently, effectively monitoring the PAH content in plastics used in electronic equipment is crucial for preventing indoor contamination.In this study we aimed to develop a fast, inexpensive, easy, and environmentally friendly analysis method for determining PAH content in plastic equipment. A dispersive liquid liquid microextraction (DLLME) combined with solidified organic drop (SFO) microextraction technique was developed.Considering the eleven number of parameters that can affect the signal in the DLLME-SFO method, Plackett Burmann's design was applied to select the most three impactful parameters for 18 PAH species. A Box-Behnken experimental design was also applied to optimize the identified parameters. The optimal conditions for the most influential parameters such as solvent type, pH, and the sample weight were identified as 1-dodecanol, 12 and 0.24 g, respectively.The proposed method was validated under these optimized conditions, yielding low detection limits ranging from 0.004 to 0.11 ng mL−1. The calibration curves were linear with correlation coefficients above 0.98 and relative standard deviation (RSD) values ranging from 2.4% to 20%. This method was successfully applied to analyze PAH content in the plastic components of electronic devices. The extraction technique developed in this study is a newly developed technique and has not been previously used to analyze organic pollutants that may be present in electronic equipment plastic.

Natural deep eutectic solvent-based dispersive liquid-liquid microextraction of pesticides in drinking waters combined with GC-MS/MS detection

The current research aims to develop a new analytical method applying a dispersive liquid-liquid microextraction (DLLME) assisted by vortex and using an environmentally friendly extractant for the preconcentration of organochlorine and organophosphorus pesticides followed by gas chromatography-tandem mass spectrometry (GC-MS/MS) analysis. The extractant (i.e., natural deep eutectic solvent (NADES)) is safe, cheap, biodegradable and can be prepared by simply mixing DL-menthol and decanoic acid (molar ratio 2:1). The main experimental factors affecting the extraction of all analytes evaluated (19 organochlorine and organophosphorus pesticides) have been optimised using a multivariate analysis consisting in two steps: a Plackett-Burman design followed by a central composite design (CCD). Seven experimental factors have been evaluated: (i) sample volume; (ii) NADES volume; (iii) sample pH; (iv) extraction time; (v) centrifugation time; (vi) centrifugation speed; and (vii) ionic strength (NaCl %, w v−1). For the significant variables, the optimum values were 10 mL sample and 45 μL NADES. No pH adjustment as well as addition of NaCl were needed. The other variables were set at 3 min extraction time, 5 min centrifugation time and 900×g centrifugation speed, respectively. Under the optimised extraction conditions, the limit of quantification (LOQ) values ranged between 0.2 and 78 ng L−1 for all analysed pesticides. Furthermore, the proposed analytical method has been successfully applied to drinking water (bottled spring water). The recovery study (n = 3) has been evaluated at 0.1, 1.0 and 5.0 μg L−1 spiking levels, obtaining relative recovery values within the range of 70 % and 117 % and RSD values between 1 % and 20 % for all the analytes studied, except for p,p-DDT (56–77 % in high conductivity water samples).

Handshake of deep eutectic solvent and ionic liquid: Two liquid-liquid microextraction procedures for plant analysis

Plants are subjects of interest due to the secondary metabolites in their extracts which are promising as new pharmaceuticals. Phytochemistry do not have united system of sample preparation or analysis still due to different structure of plant cells, wide broad range of chemical properties and concentrations of bioactive compounds. Such challenges can be addressed in a green chemistry manner using new approaches through smart materials in routine monitoring and researches. Liquid smart materials, such as ionic liquids (ILs) and deep eutectic solvents (DESs) are attractive due to flexible properties, lots of extraction approaches, recycle potential, and direct compatibility with powerful analytical methods.In this study DES-based microextraction procedure with pH-switching was developed. Four choline chloride DESs were suggested as selective extraction phases for polar compounds from acetonitrile extracts. Method was successfully tested on four plants (Iris sibirica L., Hypericum perforatum L., Scutellaria baicalensis G, Citrus reticulata B.). Developed procedure was optimized and validated for the choline chloride – urea (1:2 mol/mol) DES that demonstrated better results in extraction. LOD for rutin was found as 0.05 mg ml−1. For low-polar compound, imidazolium ionic liquid-based dispersive liquid-liquid microextraction procedure was developed. 1-hexyl-3-methylimidazolium salts have demonstrated desired selectivity. The main factors influencing the extraction efficiency have been identified and optimized by design of experiment on two model plants (Iris sibirica L. and Scutellaria baicalensis G.). Validation procedures were done for thymol. LOD for thymol was found as 0.021 mg ml−1.The methods were compared with each other and traditional methanol extraction. The selectivity of the smart materials supports each other, usage of such extraction phases provides same or better results as obtained with methanol.

Natural deep eutectic based dispersive liquid-liquid microextraction and solidified floating organic drop for cadmium determination by electrothermal atomic absorption spectrometry with multivariate optimization (DLLME-SFOD-NADES-ETAAS)

A novel method was developed for cadmium determination based on dispersive liquid-liquid microextraction and solidified floating organic drop by multivariate optimization with electrothermal atomic absorption spectrometric detection using a natural deep eutectic solvent (NADES) of (L)-menthol and formic acid. Important factors, including pH, final concentration of PAN, mole ratio of formic acid, volume of NADES, type of dispersive solvent, and vortex time, were assessed using two-level fractional factorial design (FFD), and circumscribed central composite design (CCC). The analytical performance parameters, encompassing linearity range, limit of detection (LOD), limit of quantification (LOQ), and precision, were evaluated. The linearity range ranged from 0.72 to 2.50 ng/L, with corresponding LOD and LOQ values of 0.22 and 0.72 ng/L, respectively. Precision was evaluated by conducting three replicates of the three concentration levels, resulting in %RSD values of 11.8 %, 5.1 %, and 3.9 %, respectively. An enrichment factor (EF) of 112 was achieved. The optimized method was applied for cadmium determination in various matrices, including drinking water, environmental water, seafoods, yielding %recovery in the ranges of 78.05–102.41 %. Finally, comparison of t-values between the developed method and CRMs demonstrated satisfactory results at a 95 % confidence level.

Spectrophotometric Determination of Cobalt(II) by Natural Deep Eutectic Solvent (NADES) Air-Assisted Dispersive Liquid-Liquid Microextraction (AA-DLLME)

Cobalt is beneficial for human activity but has adverse effects when discharged in large quantities. Therefore, its precise and accurate quantification in samples is of importance. Here, a natural deep eutectic solvent (NADES), composed of camphor (H-bond acceptor) and menthol (H-bond donor), has been used for the preconcentration of Co(II) from water samples before determination by a spectrophotometer at 398 nm. The 8-hydroxyquinoline-Co(II) complex was transferred to the NADES using air-assisted dispersive liquid-liquid microextraction (AA-DLLME). The extraction efficiency was enhanced through fine tuning of various parameters, including pH, NADES volume, and quantity of dispersant. Similarly, the centrifugation rate and time, quantity of the complexing agent, matrix effects, and salt concentration were also evaluated. Under the optimized conditions, an enrichment factor of 37.5 and a preconcentration factor of 37.5 were obtained. The limits of detection (LOD) and quantification (LOQ) were 0.44 µg/L and 1.47 µg/L, respectively. For seven replicates of 50 µg/L Co(II), the relative standard deviation was 3.2%. The developed method was employed for the determination of Co(II) in water samples, with quantitative recovery values from 94.5 to 98.5%.

Development and validation of a DLLME-HPLC-FLD method for determination of aflatoxins in Chrysanthemum morifolium based on quality by design principles.

Aflatoxins, potent carcinogens produced by Aspergillus species, present significant health risks and commonly contaminate herbal products such as Chrysanthemum morifolium. Detecting these toxins in C. morifolium proves challenging due to the complex nature of the herbal matrix and the fluctuating levels of toxins found in different samples. This study aimed to develop and optimize a novel method for the detection of aflatoxins in C. morifolium using dispersive liquid-liquid microextraction combined with high-performance liquid chromatography-fluorescence detection based on quality by design principles. The method involved determining critical method attributes and parameters through the Plackett-Burman design, followed by optimization using the Box-Behnken design. Monte Carlo simulation was employed to establish a design space, which was experimentally verified. Method validation was performed to confirm accuracy, precision, and stability. The developed method exhibited excellent linearity (R2 > 0.9991) for aflatoxins B1, B2, G1, and G2 across a range of concentrations, with recovery rates between 85.52% and 102.01%. The validated method effectively quantified aflatoxins in C. morifolium under different storage conditions, highlighting the impact of temperature and storage time on aflatoxin production. This study successfully established a reliable and effective method for the detection of aflatoxins in C. morifolium, highlighting the importance of strict storage conditions to reduce aflatoxin contamination. Using a quality by design framework, the method demonstrated robustness and high analytical performance, making it suitable for routine quality control of herbal products.

Alcohol-based hydrophobic deep eutectic solvents and ultrasound-assisted liquid phase microextraction followed by GC-MS for the extraction and analysis of organophosphorus pesticides in the blood of farmers.

Organophosphorus pesticides (OPPs) are a group of pesticides that are most widely used in the agricultural sector, and farmers are exposed to these chemicals more than other members of society. In this work, an environmentally friendly, simple, and safe ultrasound-assisted dispersive liquid-liquid microextraction (USA-DLLME) method using alcohol-based hydrophobic deep eutectic solvents (HDESs) followed by gas chromatography-mass spectroscopy (GC-MS) was developed for the extraction and determination of OPPs in the blood of farmers studied in Ravansar cohort. DESs synthesized from thymol as hydrogen bond donor (HBD) and aliphatic alcohols as hydrogen bond acceptor (HBA) have been used as extractants. Under optimal experimental conditions, the reproducibility of the method based on 7 replicate measurements of 10 µg L-1 of OPPs in blood samples was in the range of 1.4-3.8%. The method showed a linearity in the range of 0.01-150 µg L-1. The limits of detection and limits of quantification were between 0.003 and 0.02 µg L-1 and 0.01-0.05 µg L-1, respectively. The matrix effect and accuracy of the method were confirmed by spiking different amounts of OPPs in real blood samples and obtaining relative recoveries in the range of 91-112%. The results showed that the concentration of OPPs in the case group was significantly higher than in the control group, which is because the case group was exposed to OPPs during the spraying of agricultural products.

Effervescence tablets based on magnetic ionic liquids as simple microdevices for the in situ dispersive liquid-liquid microextraction of urinary biomarkers

BackgroundMagnetic ionic liquids (MILs) have been explored in dispersive liquid-liquid microextraction (DLLME). Their usage allows to substitute centrifugation and/or filtration steps by a quick magnetic separation. Besides, effervescence-assisted DLLME is one of the most known options to improve the dispersion of the extractant in the sample, while allowing to avoid the consumption of external energy during dispersion. Despite these interesting features, only one study incorporates MILs containing the tetrachloroferrate anion in effervescence tablets. These MILs are highly viscous and liquid at room temperature, thus compromising the stability of the tablets when used as extraction microdevices in effervescence-assisted DLLME, and only allowing their use in the conventional MIL-DLLME mode. ResultsA new class of effervescence tablets containing a Ni(II)-based MIL, that is solid at room temperature, is here proposed. This type of tablets permits their use, for first time, in the in situ DLLME mode, occurring through the transformation of a water-soluble MIL into a water-insoluble MIL microdroplet. This way, the tablet formulation included: the MIL, the metathesis reagent lithium bis[(trifluoromethyl)sulfonyl]imide, NaH2PO4 and K2CO3 as effervescence precursors salts, and Na2SO4 as salting-out and desiccating agent. The method is combined with high-performance liquid-chromatography and both fluorescence and ultraviolet detection, for the determination of monohydroxylated polycyclic aromatic hydrocarbons (OH-PAHs) and benzophenones (BPs), as biomarkers in urine. The method simply involved the addition of the effervescence tablet to the sample, thus taken place simultaneously the effervescence process and the metathesis reaction, without requiring any external energy consumption. The method presented limits of detection down to 10 ng L−1 for OH-PAHs and to 0.60 μg L−1 for BPs, inter-day relative standard deviations lower than 17 %, and average relative recoveries of 94 % in urine. The determined OH-PAHs contents in urine were between 0.40 and 16 μg L−1, and between 17.8 and 334 μg L−1 for BPs. SignificanceWe have developed the first MIL-based effervescence tablets that are completely solid, thus improving the stability and robustness of these microdevices with respect to previously reported tablets involving MILs, while permitting to perform into the in situ DLLME mode (thus gaining in extraction efficiency). This approach including the MIL-based effervescence tablets constitutes an alternative on-site platform for the analysis of urine, as satisfactory precision, accuracy, and sensitivity are achieved despite not involving any external energy input within the analytical sample preparation setup. This method also constitutes the first application of MIL-based effervescence tablets for bioanalysis.

Efficient Green Solvent Extraction and Bioassay Studies of Favipiravir in Rat Dried Blood Spots Using Ionic Liquid-Based Dispersive Liquid-Liquid Microextraction (IL-DLLME) Coupled with HPLC-PDA: Application to Bioequivalence Studies

Background: Favipiravir is an antiviral drug having pyrazine group moiety. It is a reliable and an efficient green solvent, and a highly recoverable bio-sampling method is required for it. It is widely used in COVID-19 treatment for the prevention of the spread of viral infections in the body Objective: This proposed green solvent (ionic liquid)-based bioassay study aimed to quantify favipiravir in rat-dried blood spots using Dispersive Liquid-liquid Microextraction (IL-DLLME). Methods: The proposed bioassay separation was achieved through an isocratic elution mode using a hybrid silica-based ODS column (250 × 4.6 mm; 5 μm), a column temperature of 25°C, an injection volume of 10 μL, a flow rate of 1.0 mL/min, and a detector wavelength set at 310 nm. The run time was less than 10 minutes. Mobile phase was delivered with acetonitrile, methanol, and 10 mM Na2HPO4 at pH 4.0 ± 0.5, (15: 20: 65, v/v/v). In a microtube, 50 mL of Ionic Liquid (IL), 500 μL of disperser ACN, 50 μL of 10% NaCl, and IS (20 ng mL-1) were added to perform the Dried Blood Spot (DBS) sample extraction methodology. The advantages of the proposed methodology have been found to include minimum hematocrit effect and an adequate blood volume for testing, easy transportation, and significant extraction recovery. The sample analysis has been carried out using HPLC-PDA with oseltamivir used as an internal standard. Results: We have investigated the important variables, i.e., salt concentration (10% NaCl, analyte recovery being higher) and disperser solvent [50μL of BMIHP plus 500 μL of ACN (v/v) yielding the highest recovery], in the extraction process. Extraction Recovery (ER) and Enrichment Factor (EF) were also evaluated using the IL-DLLME method. The calibration curve examined a range of 0.5-150 μg/mL, with a lower Limit of Quantification (LOQ) being 0.5 μg/mL in QC as well as calibration samples, respectively. Conclusion: Significant bioanalytical validation has been performed and all the parameters have been evaluated systematically as per bioanalytical method validation protocols, i.e., US FDA- 2018 guidelines. The following analytical parameters have been covered: standard curve, limit of quantification, range, recovery, stability, accuracy, precision, sensitivity, ER, EF, and selectivity. The developed bioassay method has been successfully applied in the pharmacokinetic studies of rats and successfully applied in bulk drugs.