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Conventional methods for detecting unsaturated fatty acids (UFAs) pose challenges for rapid analyses due to the need for complex pretreatment and expensive instruments. Here, we developed an intelligent platform for facile and low-cost analysis of UFAs by combining a smartphone-assisted colorimetric sensor array (CSA) based on MnO2 nanozymes with "image segmentation-feature extraction" deep learning (ISFE-DL). Density functional theory predictions were validated by doping experiments using Ag, Pd, and Pt, which enhanced the catalytic activity of the MnO2 nanozymes. A CSA mimicking mammalian olfactory system was constructed with the principle that UFAs competitively inhibit the oxidization of the enzyme substrate, resulting in color changes in the nanozyme-ABTS substrate system. Through linear discriminant analysis coupled with the smartphone App "Quick Viewer" that utilizes multihole parallel acquisition technology, oleic acid (OA), linoleic acid (LA), α-linolenic acid (ALA), and their mixtures were clearly discriminated; various edible vegetable oils, different camellia oils (CAO), and adulterated CAOs were also successfully distinguished. Furthermore, the ISFE-DL method was combined in multicomponent quantitative analysis. The sensing elements of the CSA (3 × 4) were individually segmented for single-hole feature extraction containing information from 38,868 images of three UFAs, thereby allowing for the extraction of more features and augmenting sample size. After training with the MobileNetV3 small model, the determination coefficients of OA, LA, and ALA were 0.9969, 0.9668, and 0.7393, respectively. The model was embedded in the smartphone App "Intelligent Analysis Master" for one-click quantification. We provide an innovative approach for intelligent and efficient qualitative and quantitative analysis of UFAs and other compounds with similar characteristics.

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This study compares two groups of university students with differing instructions participating in an object drawing task as a part of an art therapy-based self-help online intervention. The intervention aimed to help participants enhance positive mood and subjective feeling of self-control and reduce negative mood. The object task contained suggestive elements in the instructions similar to self-hypnosis with an indirect and a direct way of formulation. Quantitative (positive affect and negative affect scale and Self-Assessment Manikin scale) and qualitative methods (text and picture rating) were used to investigate the difference between the outcome effects on the two groups. The results found a significant decrease in negative mood for indirect suggestion, while a significant increase of positive mood for the direct suggestion condition. Based on qualitative analyses, findings indicated that hidden implications in the art-making instructions modified the chosen imaginary and emotional changes related to art-making. Suggestions in the instructions can make a difference in one's mood and this should also be considered while designing guidelines for self-hypnosis.

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Images, texts, voices, and signals can be synthesized by latent spaces in a multidimensional vector, which can be explored without the hurdles of noise or other interfering factors. In this paper, we present a practical use case that demonstrates the power of latent space in exploring complex realities such as image space. We focus on DaVinciFace, an AI-based system that explores the StyleGAN2 space to create a high-quality portrait for anyone in the style of the Renaissance genius Leonardo da Vinci. The user enters one of their portraits and receives the corresponding Da Vinci-style portrait as an output. Since most of Da Vinci's artworks depict young and beautiful women (e.g., "La Belle Ferroniere", "Beatrice de' Benci"), we investigate the ability of DaVinciFace to account for other social categorizations, including gender, race, and age. The experimental results evaluate the effectiveness of our methodology on 1158 portraits acting on the vector representations of the latent space to produce high-quality portraits that retain the facial features of the subject's social categories, and conclude that sparser vectors have a greater effect on these features. To objectively evaluate and quantify our results, we solicited human feedback via a crowd-sourcing campaign. Analysis of the human feedback showed a high tolerance for the loss of important identity features in the resulting portraits when the Da Vinci style is more pronounced, with some exceptions, including Africanized individuals.

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BACKGROUND: Shengmai Formula (SMF), a classic formula in treating Qi-Yin deficiency, is composed of Ginseng Radix et Rhizoma Rubra (GRR), Ophiopogon Radix (OR), and Schisandra chinensis Fructus (SC), and has been developed into various dosage forms including Shengmai Yin Oral Liquid (SMY), Shengmai Capsules (SMC), and Shengmai Injection (SMI). The pharmacological effects of compound Chinese medicine are attributed to the integration of multiple components. Yet the quality criteria of SMF are limited to monitoring schisandrol A or ginsenosides Rg1 and Re, but none for OR. Since the complexity of raw materials and preparations, establishing a economical and unified method for SMF is challenging. It is urgent to simultaneously quantify multiple components with different structures using a universal method for quality control of SMF. Charged aerosol detector (CAD) overcame the above shortcomings owing to its characteristics of high responsiveness, nondiscrimination, and low cost. PURPOSE: We aimed to establish a versatile analysis strategy using HPLC-CAD for simultaneously quantifying the structurally diverse markers in quality control of SMF from raw materials to preparations. METHOD: By optimizing the column, mobile phase, column temperature, flow rate, and CAD parameters, a HPLC-CAD method that integrated multi-component characterization, authenticity identification, transfer information of raw materials and quantitative determination of Shengmai preparations was established. RESULTS: In total 50 components from SMF were characterized (28 in GRR, 13 in SC, and 9 in OR). The differences in raw materials between species of SC and Schisandrae sphenantherae Fructus (SS), processing methods of Ginseng Radix (GR) and GRR, and locations of OR from Sichuan (ORS) and Zhejiang (ORZ) were compared. Fourteen components in 19 batches of SMY, SMC and SMI from different manufacturers were quantified, including 11 ginsenosides and 3 lignans. The multivariate statistical analysis results further suggested that Rb1, Rg1 and Ro were the main differences among Shengmai preparations. CONCLUSION: The established versatile analysis strategy based on HPLC-CAD was proven sensitive, simple, convenient, overcoming the discriminatory effect of UV detector, revealing the composition and transfer information of SMF and applicable for authentication of the ingredient herbs and improving the quality of Shengmai preparations.

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Rapid detection of airborne pathogens is crucial in preventing respiratory infections and allergies. However, technologies aiming to real-time analysis of microorganisms in air remain limited due to the sparse and complex nature of bioaerosols. Here, we introduced an online bioaerosol monitoring system (OBMS) comprised of integrated units including a rotatable stainless-steel sintered filter-based sampler, a lysis unit for extracting adenosine triphosphate (ATP), and a single photon detector-based fluorescence unit. Through optimization of the ATP bioluminescence method and establishment of standard curves between relative luminescence units (RLUs) and ATP as well as microbial concentration, we achieved simultaneous detection of bioaerosols' concentration and activity. Testing OBMS with four bacterial and two fungal aerosols at a sampling flow rate of 10 to 50 L/min revealed an outstanding collection efficiency of 95 % at 30 L/min. A single OBMS measurement takes only 8 min (sampling: 5 min; lysis and detection: 3 min) with detection limits of 3 Pcs/ms photons (2.9 × 103 and 292 CFU/m3 for Staphylococcus aureus and Candida albicans aerosol). In both laboratory and field tests, OBMS detected higher concentrations of bioaerosol compared to the traditional Andersen impactor and liquid biosampler. When combined OBMS with loop-mediated isothermal amplification (LAMP), the bioaerosol can be qualitative and quantitative analyzed within 40 min without the cumbersome procedures of sample pretreatment and DNA extraction. These results offer a high compressive and humidity resistance membrane filtration sampler and validate the potential of OBMS for online measurement of bioaerosol concentration and composition.

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Light stabilizers are commonly used as additives in mulching films and have environmental persistence, bioaccumulation and ecotoxicity. However, their occurrence and distribution in mulching films and accumulation in mulched soils are seldom reported. This study firstly presents a comprehensive screening of 19 light stabilizers in 65 mulching films and 30 farmland soils collected in China, of which five and eight light stabilizers were 100% detected, respectively. The light stabilizer concentration in biodegradable mulching films was significantly higher than that in polyethylene ones, with median concentrations of 1.75 × 106 µg/kg and 4.86 × 103 µg/kg, respectively. Furthermore, a positive correlation was observed between the light stabilizer concentration in mulching films and in soils. This indicates that mulching films play a critical role in the accumulation of light stabilizers in farmland soils, and biodegradable mulching films significantly increase benzotriazole light stabilizers in soils. Although the light stabilizer concentration in farmland soil is relatively low, the sustainable quantities of mulching film input and the long-term accumulation will still pose a threat to the ecological environment and organism health. Consequently, our work reveals the occurrence and environmental risk of light stabilizers in mulching films and farmland soils and brings attention to light stabilizers in the soil environment.

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BACKGROUND: Donor-recipient size mismatch (DRSM) is considered a crucial factor for poor outcomes in liver transplantation (LT) because of complications, such as massive intraoperative blood loss (IBL) and early allograft dysfunction (EAD). Liver volumetry is performed routinely in living donor LT, but rarely in deceased donor LT (DDLT), which amplifies the adverse effects of DRSM in DDLT. Due to the various shortcomings of traditional manual liver volumetry and formula methods, a feasible model based on intelligent/interactive qualitative and quantitative analysis-three-dimensional (IQQA-3D) for estimating the degree of DRSM is needed. AIM: To identify benefits of IQQA-3D liver volumetry in DDLT and establish an estimation model to guide perioperative management. METHODS: We retrospectively determined the accuracy of IQQA-3D liver volumetry for standard total liver volume (TLV) (sTLV) and established an estimation TLV (eTLV) index (eTLVi) model. Receiver operating characteristic (ROC) curves were drawn to detect the optimal cut-off values for predicting massive IBL and EAD in DDLT using donor sTLV to recipient sTLV (called sTLVi). The factors influencing the occurrence of massive IBL and EAD were explored through logistic regression analysis. Finally, the eTLVi model was compared with the sTLVi model through the ROC curve for verification. RESULTS: A total of 133 patients were included in the analysis. The Changzheng formula was accurate for calculating donor sTLV (P = 0.083) but not for recipient sTLV (P = 0.036). Recipient eTLV calculated using IQQA-3D highly matched with recipient sTLV (P = 0.221). Alcoholic liver disease, gastrointestinal bleeding, and sTLVi > 1.24 were independent risk factors for massive IBL, and drug-induced liver failure was an independent protective factor for massive IBL. Male donor-female recipient combination, model for end-stage liver disease score, sTLVi ≤ 0.85, and sTLVi ≥ 1.32 were independent risk factors for EAD, and viral hepatitis was an independent protective factor for EAD. The overall survival of patients in the 0.85 < sTLVi < 1.32 group was better compared to the sTLVi ≤ 0.85 group and sTLVi ≥ 1.32 group (P < 0.001). There was no statistically significant difference in the area under the curve of the sTLVi model and IQQA-3D eTLVi model in the detection of massive IBL and EAD (all P > 0.05). CONCLUSION: IQQA-3D eTLVi model has high accuracy in predicting massive IBL and EAD in DDLT. We should follow the guidance of the IQQA-3D eTLVi model in perioperative management.

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In order to obtain comprehensive quality evaluation of one traditional Chinese patent medicine of Mailuoning oral liquid (MLN), one smart strategy combined by fingerprint, qualitative and quantitative analyses were carried out in this study. Firstly, the fingerprints of MLN were established by HPLC-UV and HPLC-ELSD, and explained the similarity of twenty-seven batches of MLN by similarity analysis (SA). Secondly, qualitative analysis was performed by high performance liquid chromatography coupled with quadrupole-time-of-flight mass spectrometry (HPLC-QTOF-MS/MS). A total of 60 compounds were identified or tentatively identified based on chemical standards and fragmentation information. Finally, the quantitative method based on UPLC combined with triple quadrupole mass spectrometry (UPLC-QqQ-MS/MS) was developed for the simultaneous determination of 40 target compounds. The results showed that MLN samples of different productive year were clearly discriminated and eight compounds (5-hydroxymethyl-2-furaldehyde, neochlorogenic acid, loganic acid, chlorogenic acid, cryptochlorogenic acid, caffeic acid, isoacteoside, angoroside C) were selected as differential markers for MLN. In a word, this strategy including fingerprint, identification of chemical composition and multiple-component quantification could be well applied to modern quality evaluation of MLN, which could be valuable for the further quality control of more other traditional Chinese patent medicines.

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BACKGROUND: Adolescents and young adults (AYA) with a chronic somatic disease (CD) have a 3-fold higher risk of post-traumatic stress disorder (PTSD) than healthy controls. In addition, elevated post-traumatic stress symptoms (PTSS) have a negative impact on CD severity, treatment adherence, health problems and functional impairment. However, a more detailed understanding of this comorbidity is lacking. METHODS: AYA with type 1 diabetes mellitus, juvenile idiopathic arthritis or cystic fibrosis (12-21 years of age) and elevated anxiety and/or depression symptoms, as well as their reference persons (≥ 18 years of age), completed online questionnaires in self- or observer report. The most stressful event related to the CD was reported descriptively. Questionnaires were used to assess PTSS, anxious and depressive symptoms, actual overall health, coping, personal growth and social support. Qualitative content analysis, linear regression models and correlations were used for mixed methods analysis. RESULTS: According to the reports of n = 235 AYA (mean age 15.61; 73% girls) and n = 70 reference persons, four categories were identified as the most stressful events due to CD: (1) psychological burden (40% of AYA / 50% of reference persons); (2) CD self-management (32% / 43%); (3) social burden (30% / 27%); and (4) physical impairment (23% / 16%). 37% of AYA reported clinically relevant PTSS due to CD. The best predictors of PTSS severity were anxious-depressive symptoms, emotional coping, personal growth and current overall health (F(4, 224) = 59.404, R² = 0.515, p < .001). Of all categories, psychological (ß = 0.216, p = .002) and social burden (ß = 0.143, p = .031) showed significant association with the severity of PTSS (F(4, 230) = 4.489, R² = 0.072, p = .002). The more categories the most stressful event addressed, the higher was the PTSS symptom severity (r = .168, p = .010). CONCLUSIONS: Many AYA showed clinically relevant PTSS and reported experiencing stressful events in several areas of life through their CD. The association between the stressful event categories and other variables could help identify AYA with CD who need psychological interventions the most. TRIAL REGISTRATION: German Clinical Trials Register (DRKS): DRKS00016714, registered on 25/03/2019 and DRKS00017161, registered on 17/09/201.

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Toxic alkaloids are typically found in herbal medicines and have strong pharmacological effects and a broad therapeutic spectrum. On the other hand, toxic alkaloids exert toxicological activities in vivo; as such they have a narrow therapeutic window and can induce poisoning due to incorrect dose or misuse. In this view, there is an urgent need to develop a rapid and sensitive assay to detect these toxic alkaloids. This study developed a method for determining five common toxic alkaloids in blood, including brucine, strychnine, aconitine, mesaconitine, and hypaconitine using ultra-high liquid chromatography-tandem quadrupole/linear ion trap mass spectrometry (QTRAP UPLC-MS/MS). The analytes in this investigation were extracted with ether and detected using multiple reaction monitoring (MRM)-information-dependent acquisition (IDA)-enhanced product ion (EPI) scanning modes. SKF525A served as the internal standard (IS). The approach demonstrated excellent linearity, with a correlation coefficient (R) > 0.9964, and satisfactory sensitivity, with the limit of detection (LOD) of 0.31 âˆ¼ 3.26 ng/mL and a limit of quantification (LOQ) of 1.13 âˆ¼ 11.52 ng/mL. The extraction recovery (ER) was 78.8 âˆ¼ 116.2%, the matrix effect (ME) was -12.3 âˆ¼ 21.2%, and the method accuracy was 0.8 âˆ¼ 12.8%. In addition, the intra-day precision and the inter-day precision (RSD) were 0.7% ∼ 7.4% and 0.4% ∼ 13.5%, respectively. The developed approach is sensitive and efficient, and offer significant application prospect in clinical monitoring and forensic detection of poisoning.

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(10S,11S)-(-)-epi-pyriculol is a phytotoxic metabolite produced by Pyricularia grisea, a fungus identified as a foliar pathogen on the invasive weed species buffelgrass (Cenchrus ciliaris) in North America. The effective control of buffelgrass has not yet been achieved, and there is a need to develop effective and green solutions. Herbicides based on natural products and the use of phytopathogenic organisms could provide the most suitable tools for the control of weeds such as buffelgrass. Thus, one of the most relevant points to study about potential suitable phytotoxins such as (10S,11S)-(-)-epi-pyriculol is its production on a large scale, either by isolation from fungal fermentations or by synthesis. For these purposes, rapid and sensitive methods for the quantification of (10S,11S)-(-)-epi-pyriculol in complex mixtures are required. In this study, a high-pressure liquid chromatography (HPLC) method for its quantification was developed and applied to organic extracts from twelve P. grisea isolates obtained from diseased buffelgrass leaves and grown in potato dextrose broth (PDB) liquid cultures. The analysis proved that the production of (10S,11S)-(-)-epi-pyriculol is fungal-isolate dependent and strongly correlated with phytotoxic activity, shown by the P. grisea organic extracts in a buffelgrass radicle elongation test. The HPLC method reported herein allowed us to select the best strain for the production of (10S,11S)-(-)-epi-pyriculol and could be useful for selecting the best cultural conditions for its mass production, providing a tool for the use of this promising metabolite as a new bioherbicide for the control of buffelgrass.

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Renshen-Yangrong Pill (RYP) is a classical traditional Chinese medicine (TCM) preparation for the treatment of asthenic symptoms, while its multiple herbal compositions bring a wide variety of unclear chemical components which seriously hinder the effective quality control and clinical practice. The present study aimed to investigate the overall chemical profile of RYP by UPLC-LTQ/Orbitrap/MS, and further obtain the quantitative distributions of representing components in the preparations. A total of 132 components in RYP including flavonoids, triterpenoid saponins, phenylpropanoids, and monoterpenoid glycosides were identified or tentatively characterized by authentic compounds or accurate masses and fragmentation, in which 52 characteristic components were selected for further quantitation by UPLC-MS/MS. The assay was validated in terms of linearity, precision, repeatability, recovery and successfully applied for the quality control of 40 batches of RYP. Hesperidin and paeoniflorin were revealed as the most abundant constituents in RYP, and the samples of different origins and dosage forms were clearly classified based on hierarchical cluster analysis. This study provided a deep insight into the chemical profiling of RYP, as well as a new approach for determining the marker compounds, which laid a valuable foundation for further investigation of potential effective components and comprehensive quality control of RYP and related preparations.

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Recently, we confirmed that the 95% ethanol-extracted fraction of Codonopsis Radix, which contains several triterpenoids and sterols, possesses pharmacological activities. However, due to the low content and diverse types of triterpenoids and sterols, their similar structures, lack of ultraviolet absorption, and difficulty in obtaining controls, few studies have so far assessed their contents in Codonopsis Radix. We accordingly constructed an ultra-high-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry technique for the simultaneous quantitative determination of 14 terpenoids and sterols. Separation was performed on the Waters Acquity UPLC HSS T3 C18 column (100 × 2.1 mm, 1.8 µm) with 0.1% formic acid (A) and 0.1% formic acid in methanol (B) as mobile phase under gradient elution. The determination coefficients for each of the matrix calibration curves were ≥0.9925. The average recovery ranged from 81.25% to 118.05%, with relative standard deviations of <4%. The contents of 14 components in 23 batches were quantified and further analyzed through chemometrics. Linear discriminant analysis can distinguish sample varieties. The quantitative analysis method can accurately determine the contents of 14 components and thereby provide the chemical basis for the quality control of Codonopsis Radix. It also could be a valuable approach for the classification of different Codonopsis Radix varieties.

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Morphological changes induced by industrial noise have been experimentally observed in several organs. This study aims to characterize the effect of industrial noise on the pulp cell density of Wistar rats from a histological point of view, through qualitative and quantitative analysis. The histologic sections were observed over the optical microscope and photographed using 10x and 40x magnifications and analyzed using an image processing software. They refer to a group of animals exposed to industrial noise for 3 months and for 7 months (EG) and another group of animals kept in silence for control (CG) during the same periods. There was a significant decrease in pulp cell density in teeth of the animals exposed for 3 months when compared to control teeth group (p = 0.01). However, in the group exposed for 7 months, no statistically significant differences were found (p = 0.66). Even so, we found an evident relationship between exposure to industrial noise and teeth morphological changes. The observed changes are similar to the modifications found on aged teeth. Therefore, this study places industrial noise as an aggressive stimulus that can cause a reaction of the pulp-dentin complex with morphological changes compatible with premature aging of the tooth.

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Polysaccharides from natural medicines, being safe and effective natural mixtures, show great potential to be developed into botanical drugs. However, there is yet one polysaccharide-based case that has fulfilled the Botanical Guidance definition of a botanical drug product. One of the reasons is the analytical methods commonly used for qualitative and quantitative analysis of polysaccharides fall far behind the quality control criteria of botanical drugs. Here we systemically reviewed the recent advances in analytical methods. A critical evaluation of the strength and weaknesses of these methods was provided, together with possible solutions to the difficulties. Mass spectrometry with or without robust chromatographic separation was increasingly employed. And scientists have made significant progress in simplifying polysaccharide quantification by depolymerizing it into oligosaccharides. This oligosaccharides-based strategy is promising for qualitative and quantitative analysis of polysaccharides. And continuous efforts are still needed to develop a standardized quality control method that is specific, accurate, repeatable, and applicable for analyzing individual components in natural medicine formulas.

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Olive mill waste water (OMWW), a by-product created during the processing of olive oil, contains high amounts of polyphenolic compounds. If put to further use, these polyphenolic compounds could be a valuable resource for the speciality chemical industry. In order to achieve this, isolation of the polyphenolic compounds from OMWW is needed. Several techniques for this process already exist, the most widely used of which is adsorption beds. This research describes new ways of collecting polyphenolic compounds by using unmodified iron oxide (Fe3O4) particles and Fe3O4 modified with silica gel (Fe3O4@C18), citric acid (Fe3O4@CA), and sodium dodecyl sulphate (Fe3O4@SDS). This approach is superior to adsorption beds since it can be used in a continuous system without clogging, while the nano-sized shapes create a high surface area for adsorption. The results of this study show that, if used in a loop system of several adsorption and desorption cycles, (un)modified Fe3O4 has the potential to collect high concentrations of polyphenolic compounds. A combination of different modifications of the Fe3O4 particles is also beneficial, as these combinations can be tailored to allow for the removal of specific polyphenolic compounds.

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Edible bird's nest (EBN) is an expensive health food. There are many adulterants in the market. It remains challenging to discriminate EBN from its adulterants due to a lack of high-specificity markers. Besides, the current markers are confined to soluble fraction of EBN. Here, both soluble and insoluble fractions were analyzed by LC-QTOF-MS/MS. A total of 26 high-specificity peptides that were specific to EBN were selected as qualitative authentication markers. Among them, 10 markers can discriminate EBN from common adulterants, 13 markers discriminate white EBN from grass EBN/common adulterants, and 3 markers discriminate grass EBN from white EBN/common adulterants. Three of them, which showed high signal abundance (Peak area ≥ 106) and satisfactory linearity (R2 ≥ 0.995) with EBN references, were selected as the assay marker; and their peptide sequences were confidently identified by searching database/de novo sequencing. Based on these markers, a qualitative and quantitative analytical method was successfully developed and well-validated in terms of linearity, precision, repeatability, and accuracy. The method was subsequently applied to detect EBN products on the market. The results indicated that more than half of EBN products were not consistent with what the merchants claimed.

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A novel and effective method named time-resolved spectral-image laser-induced breakdown spectroscopy (TRSI-LIBS) was proposed to achieve precise qualitative and quantitative analysis of milk powder quality. To verify the feasibility of TRSI-LIBS, qualitative and quantitative analysis of milk powder quality was carried out. For qualitative analysis of foreign protein adulteration, the accuracy of models based on TRSI-LIBS was higher than those based on LIBS, with an accuracy improvement of about 5% to 10%. For the quantitative analysis of foreign protein adulteration and element content, the quantitative analysis models based on TSRI-LIBS also had better effect. For instance, limit of detection (LOD),determination coefficient of prediction (R2p), root-mean-square error of prediction (RMSEP) and average relative error of prediction (AREP) of quantitative model of calcium (Ca) content based on TRSI-LIBS improved from 1.47 mg/g, 0.95, 0.35 mg/g and 23.29% to 0.81 mg/g, 0.98, 0.20 mg/g and 12.60%.

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Vortioxetine (VOR) is a new antidepressant drug used to treat major depressive disorder. In this work, a novel, simple, rapid, accurate, precise, selective, stability-indicating, and fully validated high-performance liquid chromatography method with diode array detection (HPLC-DAD) was developed to determine VOR in bulk and pharmaceutical formulations. A Polar-RP column was used, with a mobile phase consisting of acetonitrile (ACN), methanol (MeOH), acetate buffer pH 3.5, and addition of diethylamine (DEA) in the isocratic elution mode. Assessing the stability of the VOR is fundamental to guarantee the efficacy, safety, and quality of drug products. In this study, the VOR active pharmaceutical ingredient (API) and tablets were subjected to a detailed study of forced degradation, using several degrading agents (acid, alkaline, water, heat, light, and oxidation agents). The developed HPLC-DAD method allows the collection of all the essential data to determine degradation kinetics. It was found that the decomposition of vortioxetine is fragile towards oxidative conditions and photolysis, yielding the first-order and second-order kinetic reaction in the above stress conditions, respectively. The degradation products (DPs) were identified by the high-resolution liquid chromatography coupled with electrospray ionization-quadrupole-time of flight-mass spectrometry (LC-ESI-QTOF-MS) method. The HPLC-DAD method was successfully applied for the quantification of VOR in tablets. Additionally, in silico toxicity prediction of the DPs was performed.

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INTRODUCTION: Aurantii Fructus Immaturus (Zhishi in Chinese) is the dried young fruit of Citrus aurantium L. (CA) and its cultivated varieties or Citrus sinensis Osbeck (CS). The content of flavonoids in different varieties of Zhishi may be significantly different. However, there is confusion about the botanical origin of Zhishi, and there is no reliable and systematic method to control Zhishi quality. OBJECTIVES: We aimed to establish an ultrahigh-performance liquid chromatography method coupled with diode-array detection and high-resolution tandem mass spectrometry (UPLC-DAD-HRMS/MS) for the quantitative analysis of 10 flavonoids in Zhishi that could be used for quality control and botanical origin identification. METHODOLOGY: A UPLC-DAD-HRMS/MS method was established for simultaneous identification and quantification of 10 flavonoids. Separation was performed on a Waters Acquity UPLC HSS T3 column (100 mm × 2.1 mm, 1.8 µm) with 0.1% formic acid and acetonitrile as mobile phase under gradient elution. MS was performed in positive and negative ionisation modes. The flavonoids in 41 batches were isolated and quantified. Zhishi of different botanical origins were identified by chemometrics. RESULTS: The results showed that the established method for the determination of 10 components was reliable and accurate. Chemometrics could be used to distinguish Zhishi of different botanical origins. There were significant differences in the contents of 10 flavonoids in samples of different botanical origins. CONCLUSIONS: The quantitative analysis method in this study can be used to accurately determine the content of 10 flavonoids and provide a chemical basis for quality control and botanical origin identification of Zhishi.

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