Shuang Hu's research while affiliated with Shanxi Medical University and other places

Based on the specific binding of drug molecules to cell membrane receptors, a screening and separation method for active compounds of natural products was established by combining phospholipase C (PLC) sensitized hollow fiber microscreening by a solvent seal with high‐performance liquid chromatography technology. In the process, the factors affecting the screening were optimized. Under the optimal screening conditions, we screened honokiol (HK), magnolol (MG), negative control drug carbamazepine, and positive control drug amentoflavone, the repeatability of the method was tested. The PLC activity was determined before and after the screening. Experimental results showed that the sensitization factors of PLC of HK and MG were 61.0 and 48.5, respectively, and amentoflavone was 15.0, carbamazepine could not bind to PLC. Moreover, the molecular docking results were consistent with this measurement, indicating that HK and MG could be combined with PLC, and they were potential interacting components with PLC. This method used organic solvent to seal the PLC greatly ensuring the activity, so this method had the advantage of integrating separation, and purification with screening, it not only exhibited good reproducibility and high sensitivity but was also suitable for screening the active components in natural products by various targets in vitro.

Fatty acids (FAs) have attracted many interests for their pivotal roles in many biological processes. Imbalance of FAs is related to a variety of diseases, which makes the measurement of them important in biological samples. Over the past two decades, mass spectrometry (MS) has become an indispensable technique for the analysis of FAs owing to its high sensitivity and precision. Due to complex matrix effect of biological samples and inherent poor ionization efficiency of FAs in MS, sample preparation including extraction and chemical derivatization prior to analysis are often employed. Here, we describe an updated overview of FA extraction techniques, as well as representative derivatization methods utilized in different MS platforms including gas chromatography-MS, liquid chromatography-MS, and mass spectrometry imaging based on different chain lengths of FAs. Derivatization strategies for the identification of double bond location in unsaturated FAs are also summarized and highlighted. The advantages, disadvantages, and prospects of these methods are compared and discussed. This review provides the development and valuable information for sample pretreatment approaches and qualitative and quantitative analysis of interested FAs using different MS-based platforms in complex biological matrices. Finally, the challenges of FA analysis are summarized and the future perspectives are prospected.

In this study, a hydroxyl‐rich ferrofluid was prepared by dispersing silica‐coated magnetic nanoparticles into a methyltrioctylammonium chloride‐glycerol deep eutectic solvent and then employed in the preconcentration of trace‐level of cinnamic acid derivatives (caffeic acid, p ‐hydroxycinnamic acid, ferulic acid, and cinnamic acid) in traditional Chinese medicine prior to high‐performance liquid chromatography analysis. The structures of the synthesized materials were characterized by X‐ray diffraction and infrared spectroscopy. The experimental parameters affecting the extraction performance, such as deep eutectic solvent composition, dosage of ferrofluid, pH of aqueous sample solution, salt concentration, extraction time, type, and volume of desorption solvent, were studied and optimized. Under the optimum conditions, the enrichment factors of four cinnamic acid derivatives were in the range of 107–114. Low detection limits (0.2–0.9 ng/mL), good precisions (relative standard deviations 1.2%–9.5%), and satisfactory recoveries (96.0%–104.7%) were achieved. Subsequently, the possible microextraction mechanism of the proposed method was explored and elucidated. It showed that the prepared ferrofluid is easily dispersed in the aqueous sample and achieved recovery after the extraction. The developed approach is a simple, convenient, and efficient method for preconcentration and determination of cinnamic acid derivatives in complex matrices.

A simple and rapid instantaneous nebulization dispersive liquid-phase microextraction method was developed, and combined with high-performance liquid chromatography for determination of the contents of seven analytes in traditional Chinese medicines. In this study, using the sprinkler device to achieve instantaneous synchronous dispersion and extraction, only one spray can rapidly achieve the concentration and enrichment of seven kinds of chalcone and isoflavones. The key factors affecting the extraction efficiency were optimized including the type and volume of extractant, the pH and salt concentration of the sample phase, and the number of dispersion. Under the optimal conditions, the enrichment factor of the target analytes ranged from 103.1 to 180.9, with good linearity and correlation coefficients above 0.9970. The limits of detection ranged from 0.02 to 0.15 ng/mL, with good accuracy (recoveries 91.1 to 108.9%) and precision (relative standard deviations 1.5-7.1%). This method has short extraction time (2 s), low organic solvent consumption and high enrichment effect, so it has a wide application prospects.

A supramolecular solvent based dispersive liquid‐liquid microextraction was proposed for extraction and determination of lignans in Forsythiae Fructus combined with HPLC. The supramolecular solvent, consisting of tetrabutylammonium bromide and n‐hexanol, was mixed with the sample solution to extract the analytes by a vortex. After accomplishing the extraction, the extraction phase was separated by centrifugation and collected for HPLC analysis. In this work, the important extraction variables such as the type and amount of extraction solvent, pH and salt amount in sample phase, and extraction time were optimized. The synthesis of supramolecular solvent was studied and its microstructure was characterized by transmission electron microscopy. Under the optimal conditions, the analytes’ enrichment factors were between 6 and 170 for the proposed procedure. Satisfactory linear ranges (r ≥ 0.99), detection limits (0.025–0.4 ng/mL), precisions (<9.2%), and accuracies (recoveries: 96.5%–104.8%) were obtained. The method has been successfully applied to the preconcentration of lignans in Forsythiae Fructus with simple and rapid operation, low cost, and environmental friendliness. This article is protected by copyright. All rights reserved

A homogeneous liquid-liquid microextraction (HLLME) was established based on a switchable deep eutectic solvent (DES) for the preconcentration and determination of six flavonoids with different polarity in "Scutellariae Radix" combined with high performance liquid chromatography (HPLC). A switchable DES composed of N,N-dimethylethanolamine (DMEA) and heptanoic acid was used as an extraction solvent in the HLLME method, which was miscible thoroughly with the aqueous sample phase initially, and then underwent rapid phase transition induced by the addition of an inorganic acid. After the extraction, the upper hydrophobic layer was recovered for HPLC analysis. Different experimental parameters were optimized, and the optimal extraction conditions were as follows: the switchable DES extraction phase, 90 µL of DMEA-heptanoic acid (1:1 mole ratio); phase-switching trigger, 100 µL of 5 mol/L HCl; 10% (w/v) of salt concentration in sample phase; extraction time, 0.3 min. Furthermore, the structures of the switchable DES and the upper hydrophobic layer were characterized by Fourier transform infrared spectroscopy, proton nuclear magnetic resonance spectroscopy and differential scanning calorimetry to illustrate the phase-switching mechanism of the extraction phase during the extraction process. Under the optimized conditions, the enrichment factors for six target analytes were between 0.4 and 104. The calibration curves were linear (r≥0.9866) in the range of 0.033-8.65 mg/L for scutellarin, 0.022-5.77 mg/L for baicalin, 0.0033-0.865 mg/L for scutellarein and wogonoside, and 0.0022-0.577 mg/L for baicalein and wogonin, respectively. Low detection limits (≤8.0 × 10-3 mg/L) and quantification limits (≤2.4 × 10-2 mg/L) as well as good precisions (relative standard deviations lower than 9.2%) and acceptable accuracies (spiked recoveries 89.3-114.4%) were also obtained. The proposed method is a simple, fast, and eco-friendly sample pretreatment method.

Chlorogenic acid and caffeic acid often coexist in traditional Chinese medicines (TCMs) and play roles as antioxidation, antiviral, antitumor and anti-inflammatory agents. Due to their low content and the presence of structural analogues, they cannot be effectively separated by conventional extraction methods. Molecularly imprinted polymers, as synthesized receptors with antibody-like binding properties, have significant advantages in separating structural analogues. However, the harsh imprinting conditions easily induced the degradation of chlorogenic acid. Therefore, caffeic acid was used as an epitope template to replace chlorogenic acid for imprinting. Boronic acid-functionalized magnetic nanoparticles (MNPs) were selected as substrates, which could not only facilitate the immobilization and removal of the templates by pH regulation, but also achieve rapid separation under an external magnetic field. Tetraethyl orthosilicate was selected as an imprinting monomer which allowed for precise control of the thickness of the imprinting layer by adjusting the imprinting time. The prepared epitope-imprinted MNPs showed excellent specificity, in combination with high performance liquid chromatography, have been successfully applied to the selective separation and detection of chlorogenic acid and caffeic acid in TCMs.

A novel deep eutectic solvent - loaded magnetic solid phase extraction (DES-L-MSPE) method was proposed, which was based on the direct loading of a hydrophobic DES composed of L-menthol and lactic acid (1:2) into the pores of core-shell magnetic Fe3O4@MIL-101(Cr) nanoparticles. The function of DES was to condition the Fe3O4@MIL-101(Cr) and promote liquid phase microextraction for the analytes. Through coupling with HPLC-UV analysis, this method was utilized for the determination of six non-steroidal anti-inflammatory drugs (NSAIDs), including ketoprofen, naproxen, flurbiprofen, diclofenac sodium, ibuprofen, and mefenamic acid in environmental water samples. The influencing parameters such as type and ratio of DES, amount of adsorbent, sample solution pH, salt concentration, extraction time, elution solvent and time were investigated and optimized in detail. Under the optimal conditions, the method exhibited good linearity (5.0-1000 μg/L for ketoprofen, ibuprofen, 1.5-600 μg/L for flurbiprofen, mefenamic acid, 2.5-1000 μg/L for naproxen and 3.0-600 μg/L for diclofenac sodium with the correlation coefficients ranging from 0.9972 to 0.9993), low limits of detection (0.20-1.1 μg/L), and high precision (RSD < 8.2%). Besides, the recoveries in spiked lake and river water samples were 89.8%-110.4% and 83.8%-109.0%, respectively. Taken together, the established method was proved to be simple, fast, highly sensitive and accurate for the determination of NSAIDs from aqueous matrices.

To explore the mechanism of extraction and enrichment of three nitrophenol isomers by charge-transfer supramolecular synergistic three-phase microextraction system, a charge transfer supramolecular-mediated hollow fiber liquid-phase microextraction (CTSM-HF-LPME) combined with high-performance liquid chromatography-ultraviolet detector (HPLC–UV) method was established for the determination of real environmental water samples. In this study, the three nitrophenols (NPs) formed charge-transfer supramolecules with electron-rich hollow fibers, which promoted the transport of NPs in the three-phase extraction system and greatly increased the EFs of NPs. The relationships between the EFs of NPs and their solubility, pKa, apparent partition coefficient, equilibrium constant, and structural property parameters were investigated and discussed. At the same time, most of factors affecting the EFs of NPs were investigated and optimized, such as the type of extraction solvent, pH value of sample phase and acceptor phase, extraction time, and stirring speed. Under optimal conditions, the EFs of o-nitrophenol, m-nitrophenol, and p-nitrophenol were 163, 145, and 87, respectively. With good linearity in the range of 5 × 10⁻⁷ ~ 1 µg/mL, and the limit of detection of 0.1 pg/mL, the relative standard deviations of the method precision were lower than 7.4%, and the average recoveries were between 98.6 and 106.4%. This method had good selectivity and sensitivity, satisfactory precision, and accuracy and had been successfully applied to the trace detection of real water samples.