BACKGROUND: Personalized medicine is a rapidly revolving field that offers new opportunities for tailoring disease treatment to individual patients. The main idea behind this approach is to carefully select safe and effective medications and treatment plant based on each patient\'s unique pharmacokinetic profile. Isoniazid is a first-line anti-tuberculosis drug that has interindividual variability in its metabolic processing, leading to significant differences in plasma concentrations among patients receiving equivalent doses. This variability necessitates the creation of individualized treatment regimens as part of personalized medicine to achieve more effective therapy.
RESULTS: In this work, a deep eutectic solvent-based liquid-liquid microextraction approach for the separation and determination of isoniazid in human plasma by high-performance liquid chromatography with UV-Vis detection was developed for the first time. A new natural deep eutectic solvent based on thymol as a hydrogen bond donor and 4-methoxybenzaldehyde as a hydrogen bond acceptor was proposed as the extraction solvent. The developed microextraction procedure assumed two simultaneous processes during the mixing of the sample and extraction solvent: the derivatization of the polar analyte in the presence of 4-methoxybenzaldehyde (component of the natural deep eutectic solvent) with the formation of a hydrophobic Schiff base (1); mass transfer of the Schiff base from the sample phase to the extraction solvent phase (2). Under optimal conditions, the limits of detection and quantification were 20 and 60 μg L-1, respectively. The RSD value was <10 %, the extraction recovery was 95 %.
CONCLUSIONS: In this work, the possibility of isoniazid derivatization in the natural deep eutectic solvent phase with the formation of the Schiff base was presented for the first time. The approach provided the separation and preconcentration of polar isoniazid without the use of expensive derivatization agents and solid-phase extraction cartridges. The formation of the Schiff base was confirmed by mass spectrometry.

Residues of pesticides in milk may pose a threat to human health. This study aimed to develop a liquid-phase microextraction (LPME) method using hexafluoroisopropanol (HFIP)-based supramolecular solvent (SUPRAS) for the simultaneous extraction and purification of four pesticides (boscalid, novaluron, cypermethrin and bifenthrin) in milk. Pesticides were extracted using SUPRAS prepared with nonanol and HFIP, and the extraction efficiency was analyzed. Results showed satisfactory recoveries ranging from 80.8%-111.0%, with relative standard deviations (RSDs) of <6.4%. Additionally, satisfactory linearities were observed, with correlation coefficients >0.9952. The limits of quantification (LOQs) were in the range of 1.8 μg·L-1-14.0 μg·L-1. The established method demonstrated high extraction efficiency with a short operation time (15 mins) and low solvent consumption (2.7 mL). The HFIP-based SUPRAS LPME method offers a convenient and efficient approach for the extraction of pesticides from milk, presenting a promising alternative to conventional techniques.

Tobacco flavors are extensively utilized in traditional tobacco products, electronic nicotine, heated tobacco products, and snuff. To inhibit fungal growth arising from high moisture content, preservatives such as benzoic acid (BA), sorbic acid (SA), and parabens are often incorporated into tobacco flavors. Nonetheless, consuming preservatives beyond safety thresholds may pose health risks. Therefore, analytical determination of these preservatives is crucial for both quality assurance and consumer protection. For example, BA and SA can induce adverse reactions in susceptible individuals, including asthma, urticaria, metabolic acidosis, and convulsions. Parabens, because of their endocrine activity, are classified as endocrine-disrupting chemicals. Despite extensive research, the concurrent quantification of trace-level hydrophilic (BA and SA) and hydrophobic (methylparaben, ethylparaben, isopropylparaben, propylparaben, butylparaben, isobutylparaben, and benzylparaben) preservatives in tobacco flavors remains challenging. Traditional liquid phase extraction coupled with high performance liquid chromatography (HPLC) often results in high false positive rates and inadequate sensitivity. In contrast, tandem mass spectrometry offers high sensitivity and specificity; however, its widespread application is limited by laborious sample preparation and significant operational costs. Therefore, it is crucial to establish a fast and sensitive sample pretreatment and analysis method for the nine preservatives in tobacco flavors. In this study, a method for the simultaneous determination of the nine preservatives (SA, BA and seven parabens) in tobacco flavor was established based on three phase-hollow fiber-liquid phase microextraction (3P-HF-LPME) technology combined with HPLC. To obtain the optimal pretreatment conditions, extraction solvent type, sample phase pH, acceptor phase pH, sample phase volume, extraction time, and mass fraction of sodium chloride, were examined. Additionally, the HPLC parameters, including UV detection wavelength and mobile phase composition, were refined. The optimal extraction conditions were as follows: dihexyl ether was used as extraction solvent, 15 mL sample solution (pH 4) was used as sample phase, sodium hydroxide aqueous solution (pH 12) was used as acceptor phase, and the extraction was carried out at 800 r/min for 30 min. Chromatographic separation was accomplished using an Agilent Poroshell 120 EC-C18 column (100 mm×3 mm, 2.7 μm) and a mobile phase comprising methanol, 0.02 mol/L ammonium acetate aqueous solution (containing 0.5% acetic acid), and acetonitrile for gradient elution. Under the optimized conditions, the nine target analytes showed good linear relationships in their respective linear ranges, the correlation coefficients (r) were ≥0.9967, limits of detection (LODs) and quantification (LOQs) were 0.02-0.07 mg/kg and 0.08-0.24 mg/kg, respectively. Under two spiked levels, the enrichment factors (EFs) and extraction recoveries (ERs) of the nine target analytes were 30.6-91.1 and 6.1%-18.2%, respectively. The recoveries of the nine target analytes ranged from 82.2% to 115.7% and the relative standard deviations (RSDs) (n=5) were less than 14.5% at low, medium and high levels. The developed method is straightforward, precise, sensitive, and well-suited for the rapid screening of preservatives in tobacco flavor samples.

A novel bio-supramolecular solvent (bio-SUPRAS) based on rhamnolipids (RLs) was designed for efficient extraction of pyrethroid insecticides in water and food matrices. Benefiting from RLs as amphiphiles equipped with the attractive properties of bio-degradable, low toxicity and high stability, bio-SUPRAS was spontaneously generated through salt induced coagulation. The bio-SUPRAS was characterized by cryo-scanning electron microscope and main factors influencing the extraction performance were investigated in detail. Under the optimized conditions, the method was found to have desirable limits of detection (5∼10 μg l-1), good precision (RSDs<16.9 %) and satisfactory recovery (75.2 %∼94.3 %). More importantly, the extraction mechanism was studied by density functional theory systematically. Following greenness assessment, the technique was successfully used for enrichment of pyrethroid pesticides in real samples before HPLC-UV analysis. Thus, the method showed the outstanding merits of eco-efficient, green, time-saving, and had favorable application prospect to remove trace analytes from intricate sample matrices.

Lead (Pb) poisoning is estimated to account for 1 % of the global disease burden. The gold standard for diagnosing lead poisoning in human body relies on blood lead level (BLL), which is always performed in hospitals using expensive instruments. However, there are still many countries and regions with a lack of medical resources (without enough professional medical staff and analytical instruments). To achieve a facile diagnosis of lead poisoning by ordinary residents (without any expertise), this study conducted a research study on 810 participants to discover and validate a new lead poisoning indicator (creatinine-corrected urinary lead level, cULL) beyond BLL in non-invasive samples. A point-of-care testing (POCT) device to measure cULL was developed, equipped with liquid-phase microextraction and electromembrane extraction on a paper-based analytical device for on-site separation of lead and creatinine in the urine, using a smartphone for the quantification of analytes. The cULL as a novel indicator and the POCT device developed could be effective in reducing the risk of damage from lead contamination.

A deep eutectic solvent (DES) with the ability to change from hydrophilic to hydrophobic was designed and synthesized and applied to the determination of organophosphorus (OPP) pesticides in honeysuckle dew samples. Choline chloride, phenol, and tetrahydrofuran (THF) were used as the hydrogen bond acceptor, hydrogen bond donor, and demulsifier, respectively. Eight OPP pesticides were extracted by DES coupled with ultrasonic-assisted extraction (UA) and then chromatographed by GC-MS. DES used as an extract solvent has the advantages of high extraction efficiency, low cost, and environmental protection. Furthermore, DES is compatible with GC-MS. The single factor experiment design and Box-Behnken design (BBD) were applied to the optimization of experimental factors, including the type and composition of extraction solvent, type of demulsifier solvent, the volume of DES and THF, pH of sample solution, and ultrasonic time. Under the optimum experimental conditions, the high degree of linearity from 0.1 to 20.0 ng mL-1 (R2 ≥ 0.9989), the limits of detection from 0.014 to 0.051 ng mL-1 (S/N = 3), and the recoveries of analytes from 81.4 to 104.4% with relative standard deviation below 8.6%. In addition, the adsorption mechanism of OPPs on DES was explored by adsorption kinetic studies. These results have demonstrated that the present method has offered an effective, accurate, and sensitive methodology for OPP pesticides in honeysuckle dew samples, and this method provides a reference for the detection of pesticide residues in traditional Chinese medicine.

Despite the therapeutic properties of capsaicin for some diseases, it shows some side effects for human health. The goal of this study was to develop a precise and accurate analytical strategy for the trace determination of capsaicin in different food, biological and environmental samples including pepper, saliva and wastewater by gas chromatography-mass spectrometry (GC-MS) after spraying-based fine droplet formation-liquid phase microextraction (SFDF-LPME) and quadruple isotope dilution (ID4) method. Acetic anhydride was used as derivatizing agent, and the extraction method was used to enrich the analyte derivative to reach low detection limits. Under the optimum conditions, limit of detection (LOD) and limit of quantitation (LOQ) were determined to be 0.33 and 1.10 µg/kg, respectively. Percent recoveries calculated for SFDF-LPME-GC-MS method ranged between 84.1 and 131.7 %. After the application of ID4-SFDF-LPME-GC-MS method, percent recoveries were obtained in the range of 94.9 and 104.0 % (%RSD ≤ 2.8) for the selected samples. It is obvious that the isotope dilution-based method provided high accurate and precise results due to the elimination of errors during the derivatization, extraction and measurement steps.

Capsule phase microextraction (CPME) is an efficient bioanalytical technique that streamlines the sample preparation by integrating the filtration and stirring mechanism directly into the device. A novel composite sorbent designed to be selective towards the target analytes consisting of mixed-mode sorbent chemistry synthesized by sol-gel technology is found promising and superior to the conventional C18 sorbents. Herein we describe the encapsulation of an ionic liquid (IL)/Carbowax 20M-functionalized sol-gel sorbent (sol-gel IL/Carbowax 20 M) in the lumen of porous polypropylene tubes for the capsule phase microextraction of three phosphodiesterase-5 inhibitors namely avanafil, sildenafil, and tadalafil in human serum and urine samples. The CPME device was characterized by Scanning Electron Microscopy (SEM) and Fourier-Transform Infrared Spectroscopy (FT-IR). The experimental parameters of CPME procedure (e.g. sample pH and ionic strength, extraction time, stirring rate, elution solvent and volume) were carefully optimized to achieve the highest possible extraction efficiency for the analytes. Method validation was conducted in terms of precision, linearity, accuracy, matrix effect, lower limits of quantification, and limits of detection (LOD). The method linearity was investigated in the range of 50-1000 ng mL-1 for all analytes while the precision was less than 11.8 % in all cases. For all analytes, the LOD values were 17 ng mL-1. The IL/CW 20M-functionalized microextraction capsules could be reused at least 25 times both for urine and serum samples. The green character and the applicability of the proposed method were evaluated using the ComplexGAPI and BAGI indexes. The optimized CPME protocol exhibited reduced consumption of organic solvent and generation of waste, cost-effectiveness, and simplicity. Finally, the proposed method was successfully applied to the analysis of sildenafil in human urine after administration of drug-containing formulation.

A combination of the dispersive liquid-liquid microextraction (DLLME) method based on the total vaporization procedure and cooling-assisted organic solvent-coated thin film microextraction (TFME) was applied for extracting chlorpyrifos (as the model compound). Based on the high thermal conductivity, a nickel foam thin film with the dimensions of 5.0 mm × 5.0 mm was used as a substrate for holding the organic solvent. Supporting thin film by organic solvent increases the thickness and contact area of the film relative to TFME or single drop microextraction (SDME) alone, resulting in a dramatic increase in the extraction efficiency. To protect the organic solvent and enhance the analyte distribution coefficient between the film and the vapor phase, a cooling system was applied. The proposed design was effective due to condensing the target analyte only on the uniform cooled thin film and not on the other regions in the extraction chamber. A corona discharge ionization source-ion mobility spectrometer was employed to identify the analyte. After optimizing the effective parameters, the limits of quantification (S/N = 10) and detection (S/N = 3) were calculated 0.1 and 0.03 μg L-1, respectively, and the dynamic range was measured between 0.1 and 7.0 μg L-1, with a determination coefficient of 0.9997. For three concentration levels of 0.1, 3.0, and 7.0 μg L-1, the relative standard deviations (n = 3) as the repeatability index were to be 6 %, 5 %, and 4 % for intra-day and 9 %, 6 %, and 5 % for inter-day, respectively. The enrichment factor was also calculated to be 3630 for the analyte concentration of 1.0 μg L-1. Well water, potato, and agricultural wastewater were analyzed as the real samples and the relative recovery values were measured between 92 % and 99 %. The accuracy of the proposed technique was validated by the European Standards EN 12393 method. In this approach, two steps of analyte extraction (DLLME and TFME) were used consecutively, resulting in better preconcentration and reduced matrix interference during cleaning-up.

This study introduced an innovative magnetic effervescence-assisted microextraction method, streamlining the preparation of effervescent tablets through a one-pot method that blends a CO2 donor (Na2CO3) and an H+ donor (NaH2PO4) with bare magnetic particles (Fe3O4) and an adsorbent (hydroxylated multi-walled carbon nanotubes), followed by pressing. During the extraction process, the bare magnetic particles and adsorbent undergo in-situ self-assembly to create a magnetic adsorbent. The effervescence generates bubbles that enhance effective extraction and magnetism facilitates the easy separation of the magnetic adsorbent from the sample solution, completing the process within 4 min. Applied to organochlorine pesticide analysis in fruit juices and herbal extracts, the method exhibits excellent linearity (R2 > 0.993), sensitivity (detection limits: 0.010-0.125 ng/mL), accuracy (recoveries: 85.8-99.9%), and precision (RSDs < 9.7%) with GC-ECD. Overall, this approach stands out for its simplicity, cost-effectiveness, and suitability for on-site analysis, owing to its operational ease and independence from specialized equipment.