Discovery of Novel Cholinesterase Inhibitors Easily Crossing the Blood-Brain Barrier via Structure-Property Relationship Investigation: Methylenedioxy-Cinnamicamide Containing Tertiary Amine Side Chain.

In the present investigation, a series of dimethoxy or methylenedioxy substituted-cinnamamide derivatives containing tertiary amine moiety (N. N-Dimethyl, N, N-diethyl, Pyrrolidine, Piperidine, Morpholine) were synthesized and evaluated for cholinesterase inhibition and blood-brain barrier (BBB) permeability. Although their chemical structures are similar, their biological activities exhibit diversity. The results showed that all compounds except for those containing morpholine group exhibited moderate to potent acetylcholinesterase inhibition. Preliminary screening of BBB permeability shows that methylenedioxy substituted compounds have better brain permeability than the others. Compound 10c, containing methylenedioxy and pyrrolidine side chain, showed a better acetylcholinesterase inhibition (IC50: 1.52±0.19 µmol/L) and good blood-brain barrier permeability. Further pharmacokinetic investigation of compound 10c using ultra high performance liquid chromatography-mass/mass spectrometry (UPLC-MS/MS) in mice showed that compound 10c in brain tissue reached its peak concentration (857.72±93.56 ng/g) after dosing 30 min. Its half-life in the serum is 331 min (5.52 h), and the CBrain/CSerum at various sampling points is ranged from 1.65 to 4.71(Mean: 2.76) within 24 hours. This investigation provides valuable information on the chemistry and pharmacological diversity of cinnamic acid derivatives and may be beneficial for the discovery of central nervous system drugs.

A nonsymmetrical salamo-like fluorescence chemical sensor for selective identification of Cu2+ and B4O72- ions and practical applications.

An innovative salamo-like fluorescent chemical sensor H2L, has been prepared that can be utilized to selectively detect Cu2+ and B4O72- ions. Cu2+ ions can bind to oxime state nitrogen and phenol state oxygen atoms in the chemosensor H2L, triggering the LMCT effect leading to fluorescence enhancement. The crystal structure of the copper(II) complex, named as [Cu(L)], has been achieved via X-ray crystallography, and the sensing mechanism has been confirmed by further theoretical calculations with DFT. Besides, the sensor H2L recognizes B4O72- ions causing an ICT effect resulting in bright blue fluorescence. Moreover, the sensor has relatively high selectivity and sensitivity for Cu2+ and B4O72- ions, and the detection limits are 1.02 × 10-7 and 2.06 × 10-7 M, respectively. In addition, the good biocompatibility and excellent water solubility of the sensor H2L make it very advantageous in practical applications, using H2L powder for fingerprint visualization, using H2L to identify the phenomenon of B4O72- ions emitting bright blue fluorescence, making it an ink that can print encrypted messages on A4 paper, in addition to this, based on H2L, the real water sample was tested for Cu2+ ion recognition, and finally the test strip experiment was carried out.

A unique N-heterocyclic oligo(N,O-donor) salamo-Ni(II)-based probe for highly selective fluorescence detection of Cr2O72.

A unique fluorescent probe Ni-DAS was developed by a nitrogenous heterocyclic oligo(N,O-donor) salamo-based compound DAS. DAS exhibits AIE and ESIPT effects which are extremely infrequent in salamo-based multi-oxime compounds. In addition, Ni-DAS can be used as a fluorescent probe with high selectivity and sensitivity to recognize Cr2O72- in DMF with 80 % water content, which enhances the value of the probe for application in real environments, and outperforms most similar molecular fluorescence probes. The probe Ni-DAS can recognize Cr2O72- by oxidative hydrolysis of C = N bonds, which promotes further research on theory of C = N bond hydrolysis, and the binding ratio and recognition mechanism were verified and supported by relevant theoretical calculations (DFT & MESP). The experiments showed that the probe Ni-DAS can be used for ion detection in real environments. It provides a new strategy for the oxidative hydrolysis of C = N bond and the structure of salamo-based compounds with AIE nature, and offers new ideas for study ion recognition and acidity detection.

Rapid detection and quantification of adulteration in saffron by excitation-emission matrix fluorescence combined with multi-way chemometrics.

BACKGROUND: Saffron has gained people's attention and love for its unique flavor and valuable edible value, but the problem of saffron adulteration in the market is serious. It is urgent for us to find a simple and rapid identification and quantitative estimation of adulteration in saffron. Therefore, excitation-emission matrix (EEM) fluorescence combined with multi-way chemometrics was proposed for the detection and quantification of adulteration in saffron. RESULTS: The fluorescence composition analysis of saffron and saffron adulterants (safflower, marigold and madder) were accomplished by alternating trilinear decomposition (ATLD) algorithm. ATLD and two-dimensional principal component analysis combined with k-nearest neighbor (ATLD-kNN and 2DPCA-kNN) and ATLD combined with data-driven soft independent modeling of class analogies (ATLD-DD-SIMCA) were applied to rapid detection of adulteration in saffron. 2DPCA-kNN and ATLD-DD-SIMCA methods were adopted for the classification of chemical EEM data, first with 100% correct classification rate. The content of adulteration of adulterated saffron was predicted by the N-way partial least squares regression (N-PLS) algorithm. In addition, new samples were correctly classified and the adulteration level in adulterated saffron was estimated semi-quantitatively, which verifies the reliability of these models. CONCLUSION: ATLD-DD-SIMCA and 2DPCA-kNN are recommended methods for the classification of pure saffron and adulterated saffron. The N-PLS algorithm shows potential in prediction of adulteration levels. These methods are expected to solve more complex problems in food authenticity. © 2023 Society of Chemical Industry.

A fluorescent Salamo-Salen-Salamo-Zn(II) sensor for bioimaging and biosensing H2PO4- in Zebrafish and plants.

A newly designed and synthesized Salamo-Salen-Salamo-Zn(II) complex sensor (sensor ZT) was extensively explored for anion sensing studies. The selectivity and sensitivity of the sensor ZT towards H2PO4- ions were based on ICT and CHEF effects, and via displacement pathways in DMSO/H2O (9:1, v/v) medium in the presence of other anions like, PO43-, HPO42- and P2O74- in a short time, separately. The prepared ZT sensor has excellent association constant and low detection lines. The sensing mechanism and binding mode of the sensor were studied by UV-Vis spectroscopy, HR-MS, 1H NMR titration and theory calculations (DFT & TD-DFT) for analytes. The time response and stability of the sensor are also given. Meanwhile, the sensor ZT can be widely used as a simple and effective solid-state optical sensor to detect H2PO4- by intuitive fluorescence changes. In addition, besides the environment can be used as a powerful instrument for detecting H2PO4-, based on the good biocompatibility and tissue permeability of ZT, effectively monitoring H2PO4- in cellular distribution by confocal microscopy using Zebrafish and bean sprout.

Design, synthesis and the evaluation of cholinesterase inhibition and blood-brain permeability of daidzein derivatives or analogs.

In the present study, a series of derivatives and analogs of daidzein were designed and synthesized to investigate cholinesterase inhibition and blood-brain barrier permeability. The enzyme assay showed that most of the compounds containing a tertiary amine group exhibit moderate cholinesterase inhibition, 7-hydroxychromone derivatives (absence of B ring of daidzein scaffold) only have a weaker bioactivity, while those compounds without the tertiary amine group have no bioactivity. Among them compound 15a (4'-N,N-dimethylaminoethoxy-7-methoxyisoflavone) appeared the best inhibitory activity (IC50 : 2.14 ± 0.31 µmol/L) and higher selectivity for AChE over BuChE (Ratio: 7.07). It was selected for the further investigation by UPLC-MS/MS. The results show that CBrain/Serum of compound 15a in mice was more than 2.87 within 240 min. This discovery may provide worthy information for the future development of central nervous drugs including but not limited to cholinesterase inhibitors.

Piecewise direct standardization assisted with second-order calibration methods to solve signal instability in high-performance liquid chromatography-diode array detection systems.

In this paper, in order to solve signal instability of high-performance liquid chromatography-diode array detection (HPLC-DAD) data and maintain the second-order advantage, this work proposed piecewise direct standardization (PDS) assisted with second-order calibration methods to analyze two different complex HPLC-DAD data with signal instability, including simulated HPLC-DAD data and the data of pesticide residues in saffron. Accurate quantitative results of target analytes can be obtained by PDS combined with alternating trilinear decomposition algorithm (ATLD) and alternating trilinear decomposition assisted multivariate curve resolution algorithm (ATLD-MCR) in the presence of signal instability with time shifts and changes of peak shape. Quantitative results of the model after calibration transfer are better than those of the model established by calibration sets and prediction sets with signal instability using ATLD algorithm and ATLD-MCR algorithm under different situations. Meanwhile, t-test was used to judge whether there are significant differences between these quantitative results of models. The performances of MCR-ALS algorithm were compared with that of PDS-ATLD method and PDS-ATLD-MCR method and the proposed methods have greater potential in dealing with the case of signal instability with time shifts and changes of peak shape. In a word, this methodology can reduce the number of calibration samples for recalibration and modeling, improve the efficiency of experiment, conform to the principle of green chemistry, and obtain satisfactory quantitative results in the presence of signal instability with time shifts and changes of peak shape.

Quantitative analysis of carbaryl and thiabendazole in complex matrices using excitation-emission fluorescence matrices with second-order calibration methods.

In this paper, a fast and efficient analytical strategy was proposed that chemometrics assisted with excitation-emission fluorescence matrices was used to quantify carbaryl (CAR) and thiabendazole (TBZ) in peach, soil and sewage. Even if there are serious overlapped peaks and unknown interferences in fluorescence analysis, the second-order calibration method based on alternating trilinear decomposition (ATLD) algorithm can be used to analyze CAR and TBZ in peach, soil and sewage. The recoveries of CAR and TBZ in peach are 110.4% and 99.7% and their standard deviations are lower than 2.1% and 0.3%, respectively. In addition, the accuracy of the method was assessed with figures of merit as well as intra-day and inter-day precision. The limit of detection, the limit of quantitation of CAR and TBZ in peach are 1.2 ng mL-1 and 0.3 ng mL-1, 3.5 ng mL-1 and 0.8 ng mL-1, respectively. And their root-mean-square error of prediction are 17.0 ng mL-1 and 5.0 ng mL-1 and there are high sensitivity and selectivity in this method. Meanwhile, the results obtained by ATLD algorithm were compared with those obtained by the self-weighted alternate trilinear decomposition algorithm (SWATLD) and the parallel factor analysis (PARAFAC) algorithm, and statistical methods such as the t-test, F-test and the elliptic joint confidence region were used to evaluate for analysis. There were no significant differences among these methods. At last, high performance liquid chromatography-fluorescence detector (HPLC-FLD) was used to evaluate the accuracy and reliability of the proposed method. These results are satisfactory and indicate that the proposed method can be used for accurate and rapid determination of pesticides in complex systems.

Comparison of three chemometric methods for processing HPLC-DAD data with time shifts: Simultaneous determination of ten molecular targeted anti-tumor drugs in different biological samples.

Three intelligent chemometric multi-way calibration methods including alternating trilinear decomposition (ATLD), alternating trilinear decomposition assisted multivariate curve resolution (ATLD-MCR) and multivariate curve resolution-alternating least squares (MCR-ALS) combined with high performance liquid chromatography-diode array detection (HPLC-DAD) were used to quantify ten molecular targeted anti-tumor drugs in three complex biological matrices (plasma, urine and cell culture media matrices). All analytes can be successfully eluted in 6.5 min. In this experiment, various degrees of time shifts occurred in different samples. While slight time shifts exist in the chromatographic analysis, satisfactory results can be obtained by the three proposed methods. When the time shift was large (5.6 s), the average spiked recoveries obtained by ATLD analysis were in the range of 58.9%-116.5%, which was less than satisfactory. However, the average recoveries obtained by MCR-ALS and ATLD-MCR analysis were 89.8%-114.8% and 84.5%-106.1% respectively, and more satisfactory results were obtained. For further research, ATLD-MCR and MCR-ALS methods were compared, and the results were evaluated by statistical tests. Accuracies of concentrations obtained by them were considered to be no significant difference. In addition, compared with other methods currently published, the proposed chemometric methods combined with the HPLC-DAD can rapidly, simultaneously and accurately determine varieties of molecular targeted anti-tumor drugs in different complex biological matrices even in the presence of severe peak overlaps, severe time shifts, slight baseline drifts and different unknown background interferences.

Green synthesis of a deep-ultraviolet carbonized nanoprobe for ratiometric fluorescent detection of feroxacin and enrofloxacin in food and serum samples.

Recently, the development of a novel fluorescent (FL) nanoprobe for ratiometric detection of antibiotics in real-world samples has received more and more attention. In this article, the distinctive optical properties of deep-ultraviolet emission, a narrowed full width at half maximum (∼20 nm) and excitation-independent emission of a carbonized nanoprobe (CNP) were easily prepared by an environmentally friendly approach of solvothermal treatment using melamine as the precursor and H2O as the solvent. The obtained CNP can be further utilized as an efficient ratiometric FL nanoprobe for enrofloxacin (EFC) and feroxacin (FXC) detection based on the fact that the FL quenching of the CNP was accompanied by an FL increase with EFC/FXC based on the inner filter effect (IFE). Under the optimal conditions, excellent linear relationships existed between the relative FL intensity (FL290 nm/FL412 nm, CNP for FL290 nm and antibiotics for FL412 nm) and the concentrations of FXC and EFC in the range of 0.05-500.0 µM and 0.05-200.0 µM, with limits of detection of 21.74 and 22.43 nM (3σ/k), respectively. With the proposed ratiometric FL sensor, FXC and EFC in milk and serum samples can be rapidly and selectively analyzed without tedious pretreatment processes for real-world samples.

Excitation-emission matrix fluorescence spectroscopy coupled with multi-way chemometric techniques for characterization and classification of Chinese lager beers.

This paper proposed excitation-emission matrix fluorescence spectroscopy coupled with multi-way chemometric techniques for characterization and classification of Chinese pale lager beers produced by different manufacturers. The undiluted and diluted beer samples presented different fluorescence fingerprints. Three-way and four-way parallel factor analysis (PARAFAC) were used to decompose the skillfully constructed three-way and four-way data arrays, respectively, to further achieve beer characterization and feature extraction. Based on the features extracted in different ways, four strategies for beer classification were proposed. In each strategy, three supervised classification methods including linear discriminant analysis (LDA), partial least squares discriminant analysis (PLS-DA) and k-nearest neighbor (kNN) were used to build discriminant models. By comparison, PARAFAC-data fusion-kNN method in strategy 3 and four-way PARAFAC-kNN method in strategy 4 obtained the best classification results. The classification strategy based on four-way sample-excitation-emission-dilution level data array was proposed to solve the problem of beer classification for the first time.

Highly efficient detection of Cu2+ and B4 O7 2- based on a recyclable asymmetric salamo-based probe in aqueous medium.

An asymmetric salamo-based probe molecule (H2 L) was synthesized and characterized structurally. When DMF/H2 O (9:1) was used as the solvent, it was shown probe H2 L has high sensitivity to Cu2+ . Using high-resolution mass spectrometry and theoretical calculation, it was found that probe H2 L could form a more stable complex (1:1) with Cu2+ , the minimum limit of detection (LOD) of H2 L for Cu2+ was calculated as 9.95 × 10-8 M. In addition, probe H2 L could also be used to identify B4 O7 2- under the same detection conditions and the minimum LOD of H2 L for B4 O7 2- was calculated as 4.98 × 10-7 M. At the same time, density functional theory theoretical calculation further proved the flexibility of probe H2 L. Through the action of EDTA, probe H2 L had a cyclic ability to recognize Cu2+ , and showed a better response in the physiological pH range; probe H2 L had the characteristics of fast recognition speed and high efficiency. In addition, with probe H2 L test paper for Cu2+ and B4 O7 2- , the effect was more obvious. Meanwhile, probe H2 L can be used to quantitatively detect Cu2+ in water samples.

Exploration advantages of data combination and partition: First chemometric analysis of liquid chromatography-mass spectrometry data in full scan mode with quadruple fragmentor voltages.

A novel soft strategy for combination and partition of mass spectra data recorded at different fragmentor voltages in full scan mode of a mass spectrometer was developed to generate abundant multi-way data. It is the first time that non-linear four-way and combined three-way LC-MS data have been obtained simultaneously in a single chromatographic run. This strategy ensures that each analyte can be ionized and detected at the most appropriate MS conditions (ionization modes, fragmentor voltages) and avoids a hard chromatographic segmentation in subsequent chemometric analysis. Two different experimental datasets were analyzed to validate the feasibility and applicability of this strategy. Some simple pretreatments were carried out before LC-MS analysis to prevent potential matrix effects. Proper chemometric tools were used to resolve three-way (partitioned data) and enhanced three-way LC-MS (combined data) data, respectively. The method was assessed by comparing the analytical results obtained from the same chemometric algorithm with both combined and partitioned datasets: (1) the combined data provided the best global overall resolution, higher sensitivity and more reliable results, (2) the partitioned data provided higher selectivity for some specific analytes. The results showed that the developed method could be a soft and ingenious tool to handle the unordered but information-rich raw LC-MS data. Moreover, the proposed strategy could take extra analytical advantages in terms of higher sensitivity and more reliable quantitative results when compared with LC-MS (with single fragmentor voltage) strategy and showed nearly the same capability in analytical quality as classic LC-MS/MS method.

Rapid and simultaneous determination of three fluoroquinolones in animal-derived foods using excitation-emission matrix fluorescence coupled with second-order calibration method.

The matter of fluoroquinolone residues in various foods still arouses wide public concern nowadays. In the present work, the strategy of excitation-emission matrix (EEM) fluorescence data coupled with second-order calibration method based on alternating normalization-weighted error (ANWE) algorithm was used to determine ofloxacin, lomefloxacin and ciprofloxacin in milk powder, milk and beef. Owning the unique "second-order advantage", the ANWE-assisted analytical method was proved to successfully and eco-friendly resolve the overlapped fluorescence spectra of multi-component in complex food matrixes without tedious pretreatment steps and sophisticated high-cost instrumentations. The feasibility of the proposed method was validated by experiments. The average spiked recoveries of three fluoroquinolones range from 82.6% to 110.5% with relative standard deviations lower than 7.4%, and the limits of detection range from 0.18 and 2.41 ng mL-1. For further evaluation, analytical figures of merit such as sensitivity and selectivity, as well as the RSDs of intra-day (≦10.6%) and inter-day (≦9.4%) were calculated. The satisfactory analytical results demonstrated that the proposed strategy could be a competitive alternative for simple, rapid and simultaneous determination of multiple fluoroquinolones in animal-derived food samples.

Derivation and applications of human hepatocyte-like cells.

Human hepatocyte-like cells (HLCs) derived from human pluripotent stem cells (hPSCs) promise a valuable source of cells with human genetic background, physiologically relevant liver functions, and unlimited supply. With over 10 years' efforts in this field, great achievements have been made. HLCs have been successfully derived and applied in disease modeling, toxicity testing and drug discovery. Large cohorts of induced pluripotent stem cells-derived HLCs have been recently applied in studying population genetics and functional outputs of common genetic variants in vitro. This has offered a new paradigm for genome-wide association studies and possibly in vitro pharmacogenomics in the nearly future. However, HLCs have not yet been successfully applied in bioartificial liver devices and have only displayed limited success in cell transplantation. HLCs still have an immature hepatocyte phenotype and exist as a population with great heterogeneity, and HLCs derived from different hPSC lines display variable differentiation efficiency. Therefore, continuous improvement to the quality of HLCs, deeper investigation of relevant biological processes, and proper adaptation of recent advances in cell culture platforms, genome editing technology, and bioengineering systems are required before HLCs can fulfill the needs in basic and translational research. In this review, we summarize the discoveries, achievements, and challenges in the derivation and applications of HLCs.

Target-based metabolomics for fast and sensitive quantification of eight small molecules in human urine using HPLC-DAD and chemometrics tools resolving of highly overlapping peaks.

Chemometrics multivariate calibration coupled with high performance liquid chromatography-diode array detection (HPLC-DAD) analytical strategy was applied for fast and sensitive quantification of the eight small molecules (uric acid, creatinine, tyrosine, homovanillic acid, hippuric acid, indole-3-acetic acid, tryptophan and 2-methylhippuric acid) in human urine. The objective of this work was to get the successful resolution of the complex matrix with minimum experimental time in the presence of highly overlapping peaks, of distortions in the time and baseline aspects among chromatograms, and of the presence of unknown and background interferences. All the analysis were based on a short C18 column with the chromatographic system operating in isocratic mode and all analytes can be successfully quantified within 6 min. The second-order HPLC-DAD data acquired were handled intelligently by two typical chemometrics tools including alternating trilinear decomposition (ATLD) and multivariate curve resolution-alternating least squares (MCR-ALS). Reasonable resolution and satisfactory quantification results were obtained regardless of the complex matrix interferences from the urine samples and the second-order advantage was fully exploited. With the validation by classic HPLC method, the proposed strategy could take extra advantages such as increased selectivity and sensitivity, shorter analysis time, undemanding elution conditions and sufficiency of lower limit of quantification benefit from multivariate calibration. The method was shown as a promising means for fast and sensitive determination of small molecules in human urine and also for fast diagnosis or surveillance in related diseases.

Simultaneous and fast determination of bisphenol A and diphenyl carbonate in polycarbonate plastics by using excitation-emission matrix fluorescence couples with second-order calibration method.

A new strategy for the determination of bisphenol A (BPA) and diphenyl carbonate (DPC) in polycarbonate plastics has been proposed, combing excitation-emission matrix fluorescence and second-order chemometrics methods. The studied compounds are two of the most frequently used chemical raw materials and intermediates, which is mainly used for bio-chemical products. The method is fast and sensitive as it can avoid tedious pretreatment steps and large amounts of organic solvents consumption. Chemometrics allowed accurate and precise quantification of two target analytes even in the presence of severe spectral overlap, unknown and background interferences, which benefit from "second-order advantages" provided by chemometrics multivariate calibration. Reasonable quantification results were obtained in real plastics samples, with limits of detection for two analytes were 0.04 and 1.18 × 103 ng mL-1 and limits of quantitation were 0.11 and 3.58 × 103 ng mL-1. In addition, the average recoveries for BPA and DPC were 99.35% and 83.50% with relative standard deviation <2.30%. It was proved that the proposed method can be a useful and sensitive tool to the determination of BPA and DPC in different polycarbonate plastics with a simple sample pretreatment at low cost.

Rapid, simultaneous and interference-free determination of three rhodamine dyes illegally added into chilli samples using excitation-emission matrix fluorescence coupled with second-order calibration method.

In this study, a smart and green analytical method based on the second-order calibration algorithm coupled with excitation-emission matrix (EEM) fluorescence was developed for the determination of rhodamine dyes illegally added into chilli samples. The proposed method not only has the advantage of high sensitivity over the traditional fluorescence method but also fully displays the "second-order advantage". Pure signals of analytes were successfully extracted from severely interferential EEMs profiles via using alternating trilinear decomposition (ATLD) algorithm even in the presence of common fluorescence problems such as scattering, peak overlaps and unknown interferences. It is worth noting that the unknown interferents can denote different kinds of backgrounds, not only refer to a constant background. In addition, the method using interpolation method could avoid the information loss of analytes of interest. The use of "mathematical separation" instead of complicated "chemical or physical separation" strategy can be more effective and environmentally friendly. A series of statistical parameters including figures of merit and RSDs of intra- (≤1.9%) and inter-day (≤6.6%) were calculated to validate the accuracy of the proposed method. Furthermore, the authoritative method of HPLC-FLD was adopted to verify the qualitative and quantitative results of the proposed method. Compared with the two methods, it also showed that the ATLD-EEMs method has the advantages of accuracy, rapidness, simplicity and green, which is expected to be developed as an attractive alternative method for simultaneous and interference-free determination of rhodamine dyes illegally added into complex matrices.

Chemometrics-assisted liquid chromatography with full scan mass spectrometry for the interference-free determination of glucocorticoids illegally added to face masks.

A smart chemometrics-assisted strategy that combines the full scan mode of liquid chromatography with mass spectrometry with second-order calibration method based on alternating trilinear decomposition algorithm was developed for the rapid determination of 15 glucocorticoids including the epimers betamethasone and dexamethasone illegally added into face masks. Fifteen glucocorticoids were rapidly eluted (11 min) under a simple elution program. By means of the second-order calibration method, 15 target analytes were successfully quantified in the presence of peak overlaps, unknown interferences and baseline drifts. Notably, the epimers, namely, betamethasone and dexamethasone, were simultaneously quantified by the proposed method under a simple elution program. The average spiked recoveries for all target analytes ranged from 87.3 ± 2.2 to 119.4 ± 5.8%. The validation parameters including sensitivity, selectivity, limit of detection, limit of quantitation, and precision were calculated to validate the accuracy of the proposed method, and the quantitative analysis results were further confirmed by liquid chromatography with tandem mass spectrometry. All results proved that the proposed chemometrics-assisted liquid chromatography with mass spectrometry strategy was an accurate and fast method to determine epimers and multiple glucocorticoids in complex face mask samples.