Development of CO2-switchable deep eutectic solvent-based liquid-liquid microextraction approach: Application in urinary excretion and tissue distribution studies.

BACKGROUND: Pharmacokinetic studies are pivotal in drug development, focusing on absorption, distribution, and excretion of active compounds. Effective sample preparation methods play a crucial role in these studies. Traditional techniques like protein precipitation and liquid-liquid extraction often involve toxic solvents and are time-consuming. Recently, deep eutectic solvent (DES) has emerged as an eco-friendly alternative due to its high efficiency, low cost, and low toxicity. This study introduces a novel sample pretreatment method using CO2-switchable DES in liquid-liquid microextraction (LLME) to enhance speed, accuracy, and sensitivity in complex biological samples analysis. RESULTS: A liquid-liquid microextraction sample pretreatment method based on switchable DES combined with high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) was established for the analysis of urine and tissue samples. The method was optimized through systematic investigation of key parameters, including DES type, volume, molar ratio, pH, vortex time, gas purge time, and salt addition. The resulting procedure exhibited satisfying linearity (r2 ≥ 0.9958), good precision (RSD ≤6.01 %), desirable recovery (52.44%-98.12 %) and matrix effect (86.22%-119.30 %), and the accuracy and precision of stability were within the ±15 % limit. The proven methods were further applied to urinary excretion study and tissue distribution study of Nelumbinis plumula (NP) extract. The results indicated that the total cumulative excretion of liensinine, isoliensinine and neferine in urine within 240 h was 4.96 %, 0.66 % and 0.44 %, respectively. The tissue distribution study showed that alkaloids mainly distribute in liver, kidney, and spleen. SIGNIFICANCE: This research introduces a groundbreaking technique distinguished by its simplicity, speed, cost-effectiveness, and environmental friendliness. This approach, utilizing CO2-switchable DES as an extraction solvent for LLME, integrates deproteinization and removal of interfering molecules into a single step. This integration showcases its efficiency and convenience, demonstrating significant promise for various applications in the analysis of biological samples. Additionally, this study provides the first report on urinary excretion and tissue distribution of alkaloids from NP using a DES-LLME method. These findings offer valuable insights into the in vivo behavior of herbal medicine, enhancing understanding of pharmacological actions and facilitating clinical rational administration.

Amine Switchable Hydrophilic Solvent Vortex-Assisted Homogeneous Liquid-Liquid Microextraction and GC-MS for the Enrichment and Determination of 2, 6-DIPA Additive in Biodegradable Film.

2, 6-diisopropylaniline (2, 6-DIPA) is a crucial non-intentionally organic additive that allows the assessment of the production processes, formulation qualities, and performance variations in biodegradable mulching film. Moreover, its release into the environment may have certain effects on human health. Hence, this study developed simultaneous heating hydrolysis-extraction and amine switchable hydrophilic solvent vortex-assisted homogeneous liquid-liquid microextraction for the gas chromatography-mass spectrometry analysis of the 2, 6-DIPA additive and its corresponding isocyanates in poly(butylene adipate-co-terephthalate) (PBAT) biodegradable agricultural mulching films. The heating hydrolysis-extraction conditions and factors influencing the efficiency of homogeneous liquid-liquid microextraction, such as the type and volume of amine, homogeneous-phase and phase separation transition pH, and extraction time were investigated and optimized. The optimum heating hydrolysis-extraction conditions were found to be a H2SO4 concentration of 2.5 M, heating temperature of 87.8 °C, and hydrolysis-extraction time of 3.0 h. As a switchable hydrophilic solvent, dipropylamine does not require a dispersant. Vortex assistance is helpful to speed up the extraction. Under the optimum experimental conditions, this method exhibits a better linearity (0.0144~7.200 µg mL-1 with R = 0.9986), low limit of detection and quantification (0.0033 µg g-1 and 0.0103 µg g-1), high extraction recovery (92.5~105.4%), desirable intra- and inter-day precision (relative standard deviation less than 4.1% and 4.7%), and high enrichment factor (90.9). Finally, this method was successfully applied to detect the content of the additive 2, 6-DIPA in PBAT biodegradable agricultural mulching films, thus facilitating production process monitoring or safety assessments.

Development of a new continuous homogenous liquid phase microextraction procedure based on in-situ preparation of deep eutectic solvent; application in the analysis of aliphatic amines in urine samples by GC-MS.

In the present work, a new microextraction procedure combined with gas chromatography-mass spectrometry has been developed for the analysis of several aliphatic amines from urine sample. The sample preparation method was a continuous homogenous liquid phase microextraction that was based on in-situ preparation of 4-chlorophenol: choline chloride deep eutectic solvent. The deep eutectic solvent was prepared by passing the mixture of related compounds through a syringe barrel filled with exothermic salts (calcium chloride and potassium bromide). The released heat by dissolving the salts and increasing the solution ionic strength assists the formation of the deep eutectic solvent. The influence of various factors on the efficiency of the proposed procedure including salts amount, flow rate, pH, salting-out effect, and extraction solvent volume was studied. The calibration curves were linear broadly over the concentration range of 1.2-250 ng mL-1 with coefficient of determinations ≥0.996. The enrichment factors were in the range of 188-246 and the limits of detection and quantification were 0.16-0.37 and 0.56-1.2 ng mL-1, respectively. Based on the results, the offered method was sensitive, rapid, eco-friendly, and efficient for extracting and determining aliphatic amines in urine samples.

Detection of trace components in Xiangdan injection of Dalbergia odorifera based on microextraction and back-extraction along with bar-form-diagram strategy.

Xiangdan Injection are commonly used traditional Chinese medicine formulations for the clinical treatment of cardiovascular diseases. However, the trace components of Dalbergia odorifera in Xiangdan Injection pose a challenge for evaluating its quality due to the difficulty of detection. This study proposes a technology combining dispersive liquid-liquid microextraction and back-extraction (DLLME-BE) along with Bar-Form-Diagram (BFD) to address this issue. The proposed combination method involves vortex-mixing tetradecane, which has a lower density than water, with the sample solution to facilitate the transfer of the target components. Subsequently, a new vortex-assisted liquid-liquid extraction step is performed to enrich the components of Dalbergia odorifera in acetonitrile. The sample analysis was performed on HPLC-DAD, and a clear overview of the chemical composition was obtained by integrating spectral and chromatographic information using BFD. The combination of BFD and CRITIC-TOPSIS strategies was used to optimize the process parameters of DLLME-BE. The determined optimal sample pre-treatment process parameters were as follows: 200 µL extraction solvent, 60 s extraction time, 50 µL back-extraction solvent, and 90 s back-extraction time. Based on the above strategy, a total of 29 trace components, including trans-nerolidol, were detected in the Xiangdan Injection. This combination technology provides valuable guidance for the enrichment analysis of trace components in traditional Chinese medicines.

The selective extraction of dietary polyamines from chicken breast using the application of a lab-on-a-chip electromembrane and dispersive liquid-liquid microextraction followed by gas chromatography-mass spectrometry.

Excessive dietary polyamines (PAs), including putrescine (PUT), spermine (SPM), and spermidine (SPD), have become a worldwide concern due to their carcinogenicity and reduced shelf life. A modern miniaturized on-chip electromembrane extraction (EME) has been applied to extract these compounds from chicken breast samples. This method is based fundamentally on ionic compounds' electrostatic attraction, diffusion, and solubility in the acceptor phase. The chemical structure of polyamines enables their efficient extraction using an electric driving force on a microchip device. HCl solution (0.1 mol L-1) was applied as an aqueous acceptor solvent. Dispersive liquid-liquid microextraction was performed after EME to facilitate joining three-phase EME to GC-MS and improve the merit figures. The total ranges of 3.77-7.89 µg g-1, 3.48-7.02 µg g-1, and 0.78-2.20 µg g-1 were acquired as PUT, SPM and SPD concentrations in chicken breast, respectively. The results demonstrate that the level of PAs in fresh chicken breast samples is not concerning, but it may reduce the quality of chicken meat over time. This novel analytical technique has several advantages: high recovery, substantial quickness, remarkable selectivity, and good enrichment factors. This emerging method could be generalized to other studies to analyze different foodstuffs.

Determination of phenytoin at trace levels in domestic wastewater and synthetic urine samples by gas chromatography-mass spectrometry after its preconcentration by simple liquid-phase microextraction.

This work presents a sensitive and accurate analytical method for the determination of phenytoin at trace levels in domestic wastewater and synthetic urine samples by gas chromatography-mass spectrometry (GC-MS) after the metal sieve-linked double syringe liquid-phase microextraction (MSLDS-LPME) method. A metal sieve was produced in our laboratory in order to disperse water-immiscible extraction solvents into aqueous media. Univariate optimization studies for the selection of proper extraction solvent, extraction solvent volume, mixing cycle, and initial sample volume were carried out. Under the optimum MSLDS-LPME conditions, mass-based dynamic range, limit of quantitation (LOQ), limit of detection (LOD), and percent relative standard deviation (%RSD) for the lowest concentration in calibration plot were figured out to be 100.5-10964.2 µg kg-1, 150.6 µg kg-1, 45.2 µg kg-1, and 9.4%, respectively. Detection power was improved as 187.7-folds by the developed MSLDS-LPME-GC-MS system while enhancement in calibration sensitivity was recorded as 188.0-folds. In the final step of this study, the accuracy and applicability of the proposed system were tested by matrix matching calibration strategy. Percent recovery results for domestic wastewater and synthetic urine samples were calculated as 95.6-110.3% and 91.7-106.6%, respectively. These results proved the accuracy and applicability of the proposed preconcentration method, and the obtained analytical results showed the efficiency of the lab-made metal sieve apparatus.

Developing of an eco-friendly liquid-liquid microextraction method by using menthol-based hydrophobic deep eutectic solvent for determination of basic fuchsin dye: assessment of the greenness profile.

Herein, we aimed to develop a new environmentally friendly liquid-liquid microextraction (LLME) method based on hydrophobic deep eutectic solvent (hDES) synthesized using biodegradable dl-menthol and decanoic acid for the spectrophotometric determination of toxic basic fuchsin dye in environmental water samples. The parameters affecting the extraction efficiency such as pH, mole ratio, and volume of hDES (1:2) and type and volume of organic solvent, sample volume, times of vortex, ultrasonic bath and centrifuge, ionic strength, and matrix effect were investigated and optimized. Under optimal conditions, the calibration curve showed linearity in the range of 7.4-167 µg L-1 with a coefficient of determination of 0.9994. The limit of detection, intra-day and inter-day precision, and recovery values were 2.25 µg L-1, 2.46% and 4.45%, and 105 ± 3%, respectively. The preconcentration and enrichment factors were found to be 30 and 61.5, respectively. The proposed hDES-LLME methodology was successfully applied to the environmental water samples to detect toxic BF dye (95-105%). Finally, the ecological impact of the suggested method was evaluated using the analytical eco-scale (PPS:88), complementary green analytical procedure indexe (ComplexGAPI), and the Analytical GREEnness tool (0.63). The assessment results showed that the presented analytical method can be regarded as a green LLME approach for the determination of the BF in water.

Discrimination of Diptera order insects based on their saturated cuticular hydrocarbon content using a new microextraction procedure and chromatographic analysis.

The nature and proportions of hydrocarbons in the cuticle of insects are characteristic of the species and age. Chemical analysis of cuticular hydrocarbons allows species discrimination, which is of great interest in the forensic field, where insects play a crucial role in estimating the minimum post-mortem interval. The objective of this work was the differentiation of Diptera order insects through their saturated cuticular hydrocarbon compositions (SCHCs). For this, specimens fixed in 70 : 30 ethanol : water, as recommended by the European Association for Forensic Entomology, were submitted to solid-liquid extraction followed by dispersive liquid-liquid microextraction, providing preconcentration factors up to 76 for the SCHCs. The final organic extract was analysed by gas chromatography coupled with flame ionization detection (GC-FID), and GC coupled with mass spectrometry was applied to confirm the identity of the SCHCs. The analysed samples contained linear alkanes with the number of carbon atoms in the C9-C15 and C18-C36 ranges with concentrations between 0.1 and 125 ng g-1. Chrysomya albiceps (in its larval stage) showed the highest number of analytes detected, with 21 compounds, while Lucilia sericata and Calliphora vicina the lowest, with only 3 alkanes. Non-supervised principal component analysis and supervised orthogonal partial least squares discriminant analysis were performed and an optimal model to differentiate specimens according to their species was obtained. In addition, statistically significant differences were observed in the concentrations of certain SCHCs within the same species depending on the stage of development or the growth pattern of the insect.

High-throughput semi-automated emulsive liquid-liquid microextraction for detecting SDHI fungicides in water, juice, and alcoholic beverage samples via UHPLC-MS/MS.

Herein, a High-Throughput Semi-automated Emulsive Liquid-Liquid Microextraction (HTSA-ELLME) method was developed to detect Succinate Dehydrogenase Inhibitor (SDHI) fungicides in food samples via UHPLC-MS/MS. The Oil-in-Water (O/W) emulsion comprising a hydrophobic extractant and water was dilutable with the aqueous sample solution. Upon injecting the primary emulsion into the sample solution, a secondary O/W emulsion was formed, allowing SDHI fungicides to be extracted. Subsequently, a NaCl-saturated solution was injected in the secondary O/W emulsion as a demulsifier to rapidly separate the extractant, eliminating the need for centrifugation. A 12-channel electronic micropipette was used to achieve a high-throughput semi-automation of the novel sample pretreatment. The linear range was 0.003-0.3 µg L-1 with R2 > 0.998. The limit of detection was 0.001 µg L-1. The HTSA-ELLME method successfully detected SDHI fungicides in water, juice, and alcoholic beverage samples, with recoveries and relative standard deviations of 82.6-106.9% and 0.8-5.8%, respectively. Unlike previously reported liquid-liquid microextraction approaches, the HTSA-ELLME method is the first to be both high-throughput and semi-automated and may aid in designing pesticide pretreatment processes in food samples.

Development of a hollow fiber-liquid phase microextraction method using tissue culture oil for the extraction of free metoprolol from plasma samples.

In this research, a method known as a hollow fiber-liquid-phase microextraction was employed to extract and concentrate free metoprolol from plasma samples. The extracted analyte was subsequently determined using high-performance liquid chromatography coupled with a diode-array detector. Several parameters, including hollow fiber length, sonication time, extraction temperature, and salt addition, were investigated and optimized to enhance extraction efficiency. After extracting the analyte under optimum conditions from plasma samples, the enrichment factor and extraction recovery were 50 and 86 %, respectively. Moreover, the method exhibited detection and quantification limits of 0.41 and 1.30 ng mL-1, respectively. The analysis of real samples demonstrated satisfactory relative recoveries in the range of 91-99 %.

Development of a vortex-assisted switchable-hydrophilicity solvent-based liquid phase microextraction for fast and reliable extraction of Zn (II), Fe (II), Pb (II), and Cd (II) from various baby food products.

This manuscript describes the development of a novel liquid phase microextraction (LPME) method for the extraction and determination of Zn (II), Fe (II), Pb (II), and Cd (II) in various infant/baby food and supplements products. The method is based on vortex-assisted extraction combined with a switchable-hydrophilicity solvent (SHS) sample preparation. The SHS, which undergoes reversible phase changes triggered by pH change, enables selective extraction and easy phase separation. A flame atomic absorption spectroscopy was used in the final determination step. Optimization studies revealed, that the optimal pH of the sample solution (after digestion) during analytes extraction is 5.5. A l-proline is added to the sample (375 mM) to ensure the complexation of the target metal cations. After the complexation step, 750 µL of SHS - a N, N-Dimethylcyclohexylamine along with 0.9 mL of 2 M of acetic acid solution is added (hydrophilicity switch-on stage) and mixed manually to obtain a homogeneous solution. In the last stage, 0.45 mL of 10 M NaOH solution (hydrophilicity switch-off stage) is added to the sample solution and a vortex for 100 s is applied to ensure the effective extraction and separation of the complex containing the analytes. At this stage, a cloudy solution is immediately obtained. Finally, the effective phase separation is obtained at the centrifugation step (4000 rpm for 2 mins). The method limit of detection was as 0.03, 0.009, 0.6, and 0.2 ng/L for Zn (II), Fe (II), Cd (II), and Pb (II) respectively with RSD% below 2.0 %. The analysis of certified reference materials and real samples proved the full applicability of the method for routine analysis, contributing to the field of heavy metal analysis and ensuring the safety of baby products. According to the AGREE methodology, this method can be named as green analytical chemistry method with a score of 0.77.

Development of UV-Vis spectroscopy-based analysis method for determination of tin(IV) in epilobium parviflorum (hoary willowherb) tea using deep eutectic solvent based preconcentration.

In this study, a UV-Vis Spectroscopy-based method was developed for the determination of tin(IV) in epilobium parviflorum tea samples after preconcentration. The preconcentration process was carried out using the liquid-liquid microextraction technique. Before starting the analysis, optimization studies were carried out for the variables likely to affect the experimental results. As a result of the analyzes performed under optimum conditions, the detection limit of our method was calculated as 16.83 µg/L. The percent relative standard deviation value was calculated as 1.25% (n = 8) and linearity was found in the range of 10-1000 µg/L. Recovery experiments were performed on epilobium parviflorum tea samples using the matrix matching method. As a result of the analyzes made on teas belonging to three different brands, recovery results ranging from 92 to 117% were obtained.

Evaluate the aluminum concentrations in whey milk samples of cows from different areas using deep eutectic solvent-based ultrasound-assisted dispersive liquid-liquid microextraction method.

This study investigates the contamination of cow milk with aluminum (Al) and its potential health implications, particularly for children. Cow milk samples were collected from both nonexposed and exposed areas in Sindh, based on the source of livestock drinking water (fresh canals and groundwater). An environmental friendly deep eutectic solvent (DES) was used with ultrasonic-assisted dispersive liquid-liquid microextraction (UDLLµE) to enrich trace amounts of Al in whey milk and water samples. The enriched samples were then analyzed using inductively coupled plasma optical emission spectrometry. Certified reference materials were employed to validate the methodology, and the experimental results exhibited acceptable conformity. The DES-based dispersive liquid-liquid microextraction method was environmental friendly, devoid of acids and oxidizing agents, and used safe and inexpensive components for routine trace metal analysis in diverse samples. The resulting data revealed that Al in whey milk samples was observed in the range of 31-45 %, corresponding to (160-270) µg L-1 and (700-1035) µg L-1 in nonexposed and exposed whole cow milk samples, respectively. Additionally, it was observed that milk boiling in Al utensil for 10-20 min enhanced the Al levels from 3 to 8% of its total contents in milk samples.

Terpenes based hydrophobic deep eutectic solvents for dispersive liquid-liquid microextraction of aliphatic aldehydes in drinking water and alcoholic beverages.

Aliphatic aldehydes are a class of organic compounds containing aldehyde groups, which are widespread, and closely related to people's daily life and health. In this work, a series of terpenes based hydrophobic deep eutectic solvents were designed and synthesized using hexafluoroisopropanol as hydrogen bond donor and menthol/thymol as hydrogen bond acceptor. Then they are used as extraction solvent in dispersive liquid-liquid microextraction for extracting and determining seven aliphatic aldehydes from drinking water and alcoholic beverage combined with high performance liquid chromatography-ultraviolet. Due to the fact that these hydrophobic deep eutectic solvents are liquid at the room temperature, a density greater than that of water, a lower viscosity (≤26.10 mPa s, 25 °C), after extraction and centrifugation, the microvolume DES-rich phase in the bottom is convenient for collection and direct analysis without further dissolution or dilution with organic solvents. Some factors affecting the extraction recovery were optimized by one-variable-at-a-time and response surface methodology. Under the optimal conditions, the enrichment factors for the seven aliphatic aldehydes were 48-56. The method had good performance: linear ranges of 1.0-200, 0.5-200, 0.2-200, 0.4-400, 1.0-400, 0.4-400 and 0.4-400 µg L-1 for seven aliphatic aldehydes (r2 ≥ 0.9949), limits of detection of 0.1-0.5 µg L-1, intra-day and inter-day precisions <4.9%. The recoveries of seven aliphatic aldehydes ranged from 76.0 to 119.0%. The proposed dispersive liquid-liquid microextraction method is simple, rapid, highly efficient, and green, which effectively reduces the amount of toxic chemical reagents used and their impact on the environment. Rapid and efficient detection of aliphatic aldehydes helps ensure a healthy diet and has great application prospects in food safety analysis.

Synthesis and characterization of a novel ionic liquid for preconcentration of Brilliant Blue FCF (E 133) from some foods by ultrasound assisted temperature controlled ionic liquid dispersive liquid liquid microextraction method prior to spectrophotometric analysis; A comparative study.

In this study, a novel ionic liquid (3-(3-chloro-2-hydroxypropyl)-1-butyl-1H-imidazol-3-ium hexafluorophosphate, (IL-2) was synthesized and characterized by FT-IR, NMR (1H,13C,31P) spectroscopy, and TGA. Two microextraction methods, ultrasonic assisted ionic liquid dispersive liquid liquid microextraction (USA-IL-DLLME) and ultrasonic assisted-temperature controlled ionic liquid DLLME, have been developed for preconcentration of Brilliant Blue FCF (E133) from some food products by the sythesized IL-2. For optimization of the both methods, several parameters such as volume of IL-2, pH, temperature, ultrasonication time, extraction time, centrifugation time, and salt effect were investigated. The obtained results for both methods under optimum conditions were compared. According to these results, the best limit of detection (4.55 µg L -1), enrichment factor (58), preconcentration factor (50), linear range (15-80 µg L -1), relative standard deviation % (1.15 %) were obtained by use of USA-TC-IL-DLLME method. Furthermore, the developed USA-TC-IL-DLLME method was succesfully applied to real samples for the preconcentration of Brilliant Blue FCF.

Switchable hydrophilicity solvent-assisted solidified floating organic drop microextraction for separation and determination of arsenic in water and fish samples.

The aim of the current study was to separate and determine arsenic in water and fish samples using a novel and green solidified floating organic drop microextraction (SFODME), which is based on switchable hydrophilicity solvent (SHS)-assisted procedure followed by hydride generation atomic absorption spectrometry (HG-AAS). The 4-((2-hydroxyquinoline-7-yl)diazenyl)-N-(4-methylisoxazol-3-yl)benzene sulfonamide (HDNMBA) and tertiary amine (4-(2-aminoethyl)-N,N-dimethylbenzylamine (AADMBA) were used as ligand and SHS, respectively. The use of SHS promotes quantitative extraction of arsenic complexes into an extraction solvent (1-undecanol). Some factors that impact extraction recovery were studied. Under optimal conditions, the limit of detection (LOD) and limit of quantification (LOQ) were 0.005 µg L-1 and 0.015 µg L-1, respectively. The calibration graph was linear up to 900.0 µg L-1 arsenic, with the enrichment factor is 267. The proposed SHS-SFODME methodology for arsenic quantification in water and fish samples was successfully implemented. The environmental friendliness and safety of proposed method were approved by the Analytical Greenness Calculator (AGREE) and the Blue Applicability Grade Index (BAGI) tools.

Dispersive liquid-liquid microextraction followed by sweeping micellar electrokinetic chromatography-tandem mass spectrometry for determination of six breast cancer drugs in human plasma.

Herein, we have developed a novel method of aqueous-sample dispersive liquid-liquid microextraction (AqS-DLLME) followed by sweeping micellar electrokinetic chromatography-tandem mass spectrometry (MEKC-MS/MS) for simultaneous determination of breast cancer drugs letrozole, anastrozole, palbociclib, ribociclib, abemaciclib, and fulvestrant in human plasma. Coupling of MEKC to MS was possible due to the use of ammonium perfluorooctanoate (APFO) as a volatile surfactant. The MEKC and MS conditions were optimized to achieve a fast, sensitive, selective, and green analysis enabling full separation of the analytes within 16 min. Electrophoretic buffer was 125 mM APFO at apparent pH 10.5 in 32 % MeOH, while sheath liquid was 70 % MeOH with 0.2 % formic acid, delivered at 10 µL/min. Excellent extraction recoveries from plasma ranging from 89.4 to 104.9 % were obtained with a combination of protein precipitation and DLLME. The developed method was validated according to the ICH guidelines. Remarkable selectivity, accuracy (bias < 6.7 %), precision (RSD < 15.8 %), and stability (bias < 10.4 %) with insignificant matrix effect (RSD < 14.0 %) and no carry-over were obtained over a wide range of concentrations. Linearity with inter-day slope RSD lower than 8.7 % was demonstrated. With this method, very low concentrations could be detected after the injection of only 68.7 nL of the sample. The method was applied to plasma samples from six women currently receiving breast cancer treatment. Determined concentrations of the drugs of interest agreed with concentrations found in clinical studies, thus proving the suitability of the developed method for therapeutic drug monitoring as a superior alternative to published LC-MS methods.

Comparison of the applicability of electromembrane extraction and liquid-phase microextraction for extraction of non-polar basic drugs from different biological samples: Using clozapine as the model analyte.

Understanding and comparing the applicability of electromembrane extraction (EME) and liquid-phase microextraction (LPME) is crucial for selecting an appropriate microextraction approach. In this work, EME and LPME based on supported liquid membranes were compared using biological samples, including whole blood, urine, saliva, and liver tissue. After optimization, efficient EME and LPME of clozapine from four biological samples were achieved. EME provided higher recovery and faster mass transfer for blood and liver tissue than LPME. These advantages were attributed to the electric field disrupting clozapine binding to interfering substances. For urine and saliva, EME demonstrated similar recoveries while achieving faster mass transfer rates. Finally, efficient EME and LPME were validated and evaluated combined with liquid chromatography-tandem mass spectrometry (LC-MS/MS). The coefficient of determination of all methods was greater than 0.999, and all methods showed acceptable reproducibility (≤14%), accuracy (90%-110%), and matrix effect (85%-112%). For liver and blood with high viscosity and complex matrices, EME-LC-MS/MS provided better sensitivity than LPME-LC-MS/MS. The above results indicated that both EME and LPME could be used to isolate non-polar basic drugs from different biological samples, although EME demonstrated higher recovery rates for liver tissue and blood.

Development of salt-induced homogeneous liquid-liquid extraction using a deep eutectic solvent performed in a narrow-bore tube for the extraction of Zn(II), Cu(II), and Cd(II) ions from honey samples.

In this study, a sample preparation procedure based on salt-induced homogeneous liquid-liquid extraction performed in a narrow-bore tube was used for the preconcentration and extraction of Zn(II), Cu(II), and Cd(II) ions from honey samples. To perform the procedure, a mixture of working solution containing sodium chloride, acetonitrile, and a synthesized deep eutectic solvent (as an extraction solvent) was transferred into a narrow tube filled with solid sodium chloride up to a specific level. As the solution flowed through the tube, tiny droplets of the extraction solvent were formed at the boundary between the solution and salt layer. The droplets moved upwards in the tube and eventually collected as a distinct layer on the top of the solution. The separated phase was removed and dispersed into ionized water. After centrifugation, tiny droplets of the extraction solvent containing the analytes were sedimented at the bottom of the tube. The concentrated analytes were measured using flame atomic absorption spectrophotometry. The linear ranges and extraction recoveries were obtained in the ranges of 1.5-100 µg kg-1 and 89.6-94.8%, respectively. The detection limits ranged from 0.35 to 0.48 µg kg-1. Low relative standard deviations (C = 10 µg L-1, n = 6) of 3.1, 2.8, and 3.4% for Zn(II), Cu(II), and Cd(II), respectively, were obtained. Finally, the optimized method was successfully used in determination of concentration of the selected heavy metal ions in various honey samples.

Development of a generic sample preparation method using dispersive liquid-liquid microextraction for the monitoring of leachable compounds in hospital pharmacy-prepared prefilled drug products.

Performant sample preparation is mandatory in any leachable study to clean and preconcentrate analytes within the sample to offer the best possible extraction recovery as well the best precision for any given substance. The aim consists in developing a sample preparation method for hospital pharmacy-prepared drug products such as long-term storage prefilled syringes, vials and IV bags for the screening of leachable compounds. The Quality Control Laboratory of the Pharmacy of the Lausanne University Hospital (Switzerland) has developed a time- and cost-effective, highly sensitive, robust, and fast method using liquid chromatography coupled with high-resolution mass spectrometry (LC-HRMS) for the analysis of 205 plastic additives. An innovative setup, based on postcolumn infusion (PCI) using 2% ammonium hydroxide in methanol was used to boost the signal intensity of the analytes in MS detection. A database for extractable and leachable trace assessment (DELTA) was built to assist in the screening process of 205 plastic packaging-related compounds. The development of the sample preparation was based on 33 plastic additive candidates in different hospital pharmacy compounding solutions, and their extraction recovery rates as well as their relative standard deviation were taken into consideration. In conclusion, the developed DLLME was assigned with ultrasound assistance and triple extraction, which brought about extraction recovery rates between 67% and 92%, a good RSD <10%, and a preconcentration factor of 50×. Therefore, DLLME could be considered suitable for the semiquantitative screening of leachable additives in simple hospital pharmacy-prepared prefilled drug products.