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Rational: Aconiti Lateralis Radix Praeparata (AC) is a traditional Chinese medicine with a long history of use. However, the current research on the material basis of AC and its processed products is still not comprehensive, especially the changes in lipo-diterpenoid alkaloids (LDAs) that can be hydrolyzed into diester-diterpenoid alkaloids in AC before and after processing. This study aimed to provide material basis guidance for the clinical use of AC and its processed products by comprehensively analyzing the changes in substances between AC and its processed products., Methods: An ultra-high-performance liquid chromatography with quadrupole time-of-flight mass spectrometry (UHPLC/Q-TOF-MS/MS) approach was optimized to chemical profiling. The MS data were processed using molecular networking combined with the in-house library database to fast characterize the compounds. Multivariate statistical methods were adopted to determine the dissimilarities of components in AC and its processed products., Results: A total of 310 compounds were tentatively identified from AC, including 109 potential new alkaloids, of which 98 were potential novel LPAs. A metabolomics approach was applied to find the characteristic marker components. As a result, 52 potential chemical markers were selected to distinguish the AC samples of different extraction methods and 42 potential chemical markers for differentiating between AC and its processed products were selected., Conclusion: The results indicate that UHPLC/Q-TOF-MS/MS and Global Natural Products Social Molecular Networking coupled with multivariate analysis strategies was a powerful tool to rapidly identify and screen the chemical markers of alkaloids between the AC samples and its processed products. These results also indicate that the toxicity of water extracts of AC and its processed products were decreased. This research not only guides the clinical safe use of AC and its processed products, but also extends the application of the molecular networking strategy in traditional herbal medicine., (© 2024 John Wiley & Sons Ltd.)

Rationale: The application of infliximab (IFX) to immune-mediated disease is limited by the significant individual variability and associated clinical nonresponse, emphasizing the importance of therapeutic drug monitoring (TDM). Because of the cross-reactivity, limited linear range, and high costs, the clinical application of the previous reported methods was limited. Here, an improved high-performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS) method was developed to address the issues., Methods: This study developed an improved bioanalytical HPLC-MS/MS method coupling nanosurface and molecular-orientation limited proteolysis technology. The commercially available compound P14R was selected as the internal standard. This method was developed with fewer volume of reagents and was thoroughly validated. The validated method was applied to TDM in pediatric inflammatory bowel disease (IBD)., Results: Chromatography was performed using a Shim-pack GISS-HP C 18 metal-free column (3 μm, 2.1 × 100 mm) with a gradient elution of 0.1% formic acid in water and acetonitrile at 0.4 mL/min. Detection and quantitation were performed using electrospray ionization (ESI) and multiple reaction monitoring in the positive ion mode. The method was validated to demonstrate its selectivity, linearity, accuracy, precision, recovery, matrix effect, and stability. The method exhibited a linear dynamic range of 0.3-100 μg/mL, with intra- and inter-day precision and relative errors below 15%. The recovery and matrix effect were measured as 87.28%-89.72% and 41.98%-67.17%, respectively, which were effectively compensated by the internal standard. A total of 32 samples collected from 24 pediatric patients with IBD were analyzed using the validated method, and only 46.9% achieved the reported targeted trough level., Conclusion: This study developed an improved HPLC-MS/MS method for the quantitative determination of IFX concentration in human plasma. The accurate, reliable, and cost-effective method was validated and utilized in the analysis of clinical samples. The results confirmed the importance of TDM on IFX and the clinical application prospects of the improved method., (© 2024 John Wiley & Sons Ltd.)

In this study, using chiral L-lysine as the molecular skeleton, three kinds of L-lysine-derived gelators (G BLB , G BLF and G FLF ) were synthesized and then bonded to the surface of silica matrix (5 μm) by amide condensation to prepare a series of multifunctional chromatography stationary phases (G BLB -SiO 2 , G BLF -SiO 2 , and G FLF -SiO 2) were prepared. The L-lysine-derived gelators not only possess chiral recognition ability, but also can spontaneously form oriented and ordered network structures in liquid medium through the interaction of non-covalent bonding forces such as hydrogen bonding, π-π stacking, and van der Waals forces. The comprehensive effect of multiple weak interaction sites enhances the molecular recognition ability and further improves the separation diversity of different types of compounds on stationary phases. The separation and evaluation of chiral compounds showed that benzoin, 1-phenyl-ethanol, 1-phenyl-propanol and 6-hydroxyflavanone could be separated in normal phase mode (NPLC). The separation of different types of non-chiral compounds, such as sulfonamides, nucleosides, nucleobases, polycyclic aromatic hydrocarbons (PAHs), anilines, and aromatic acids, were achieved in hydrophilic interaction/reversed-phase/ion-exchange mode (HILIC/RPLC/IEC), and the separation of polarized compounds could be performed under the condition of ultrapure water as the mobile phase, which has the typical retention characteristics of per aqueous liquid chromatography (PALC). The effects of organic solvent content, temperature, pH value, and buffer salt concentration on the retention and separation performance of the column were investigated. Comparison of the three prepared columns showed that the separation performance (such as aromatic selectivity) could be improved by increasing the types of functional groups on the surface of the stationary phase and the number of aromatic groups. In a word, the prepared stationary phase have multiple retention properties, can simultaneously separate chiral compounds and various types of achiral compounds. This work provides an idea for developing multifunctional liquid chromatography stationary phase materials, and further expands the application of gelators in separation science., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Quaternary phosphonium compounds (QPCs) and phosphine oxides (POs) are emerging contaminants that are attracting increasing attention. In the present study, a method for the quantification of QPCs and POs in multiple environmental media was developed using ultrahigh performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Analytes were extracted from water samples using solid phase extraction, and for the solid samples, ultrasonic extraction was employed. Compared with analytical methods established by previous studies, the approach developed in this study is more suitable for the quantitative analysis of compounds along with high sensitivity. The method quantification limit reached 0.12-2.55 ng⋅L -1 in water samples and 0.004-0.10 ng⋅g -1 in solid samples. The recoveries of target analytes spiked at low, medium and high concentrations in water and solid samples were in the range of 56.4-120 %, with relative standard deviations below 20 % (n = 6). Furthermore, the validated method succeeded in applying to analyse of eight QPCs and four POs in real environmental samples. At least five QPCs and two POs were detected in each environmental medium. This quantitative method would assist in further investigations on the occurrence, migration and the source of QPCs and POs., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Geometric isomers tend to have similar polarities and differ only in molecular shape. Vigorously developing new stationary phases to meet the requirements for the separation of isomers that have similar physicochemical properties is still an urgent topic in separation science. Poly (arylene ether)-based dendrimers are known for their multifunctional branched peripheral structures and high self-assembly properties. In this paper, two amphiphilic dendritic organic small molecule gelling agents based on poly (aryl ether), PAE-ANT and PAE-PA, were prepared and conjugated to the silica surface. SiO 2 @PAE-ANT and SiO 2 @PAE-PA were used as HPLC stationary phases for the separation of non-polar shape-restricted isomers. Both stationary phases have very high molecular shape selectivity for isomers such as polycyclic aromatic hydrocarbons (PAHs), polychlorinated biphenyls (PCBs), tocopherols and carotenoids. Separation of cis-trans geometric isomers such as diethylstilbestrol and polar compounds such as monosubstituted benzenes and anilines can also be achieved. These two columns offer more flexible selectivity and higher separation performance than commercial C 18 and phenyl columns. There is a difference in molecular shape selectivity between the two stationary phases for the same analyte test probes. SiO 2 @PAE-ANT showed slightly better linear selectivity for non-polar shape-restricted isomers compared to SiO 2 @PAE-PA with Janus-type PAE-PA bonding phase. This separation behavior may be attributed to the ordered spatial structure formed by the gel factor on the surface of the stationary phase and the combined effect of multiple weak interaction centers (hydrophobic, hydrophilic, hydrogen bonding and π-π interactions). It was also possible to separate nucleoside and nucleobase strongly polar compounds well in the HILIC mode, suggesting that hydrophilic groups in PAE-ANT and PAE-PA are involved in the interactions, reflecting their amphiphilic nature. The results show that the ordered gelation of dendritic organic small molecule gelators on the SiO 2 surface, along with multiple carbonyl-π, π-π and other interactions, play a crucial role in the separating shape-restricted isomers. The integrated and ordered functional groups serve as the primary driving force behind the exceptionally high molecular shape selectivity of SiO 2 @PAE-ANT and SiO 2 @PAE-PA phases. Alterations in the structure of dendritic organic small molecule gelators can impact both molecular orientation and recognition ability, while changes in the type of functional groups influences the separation mechanism of shape-restricted isomers., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

A hybrid organic monolithic column made of poly(lauryl methacrylate-co-1,6-hexanediol dimethacrylate) and the metal-organic framework MIL-68(Al) was prepared for the first time. The column was used in capillary liquid chromatography, both in isocratic and gradient elution modes. Separation performance towards small molecules of different chemical nature (polycyclic aromatic hydrocarbons, alkylbenzenes, phenols, etc.) was studied. Monte Carlo simulations were made to both select the proper precursors to obtain empty metal-organic framework micropores in the monolithic polymer and also, to analyze the potential free access of the studied analytes into the micropores (necessary to improve mass transfer and column efficiency). The hereby synthesized metal-organic framework microcrystals allowed obtaining homogeneous hybrid monolithic columns. Adding of MIL-68(Al) (1030 m 2 g -1 BET specific surface area) increased the surface area from 3.9 m 2 g -1 for the parent monolith to 18.2 m 2 g -1 for the hybrid column containing 8 mg mL -1 of the microcrystals. Chromatographic performance of this new column was evaluated by studying retention factors, resolution, and plate counts at room temperature. Different compounds, not completely resolved in the parent monolith, were partially or completely separated after metal-organic framework addition. Using the monolithic column with only 2 mg mL -1 of MIL-68(Al), five alkylbenzenes were completely separated with very symmetrical peak shapes, resolution factors up to 3.60 and plate counts of 4300 plates m -1 for n-hexylbenzene. This value is higher than those obtained by other authors who used organic monolithic columns with embedded metal-organic frameworks to perform separations at room temperature. Additionally, nine polycyclic aromatic hydrocarbons were partially or completely resolved in gradient elution mode. The hybrid monolithic columns exhibited very good intra-day (%RSD=1.9), inter-day (%RSD=2.6), and column-to-column (%RSD=4.3) reproducibility values. Easy and fast column preparation, and versatility to efficiently separate several compounds of different chemical nature in isocratic and gradient mode, makes this new hybrid column a very good option for the analysis of small molecules in capillary (or nano) HPLC., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The main purpose of the current work was to develop a new method to evaluate and quantify sixteen polyphenol compounds from tomato fruit using high-performance liquid chromatography (HPLC). The separation of 16 polyphenols from tomato fruit was achieved in < 60 min by using a Waters Symmetry C18 column (250 × 4.6 mm i. d, 5 µm particle sizes) with a gradient system of ultrapure water (1 % acetic acid) and 100 % methanol, a temperature of 30 °C, an injection volume of 10 μL and a flow rate of 1.1 mL/min, respectively. The analytical characteristics of evaluation method provide sufficient sensitivity for all tomato polyphenols compounds within normal range 0.1-20 μg·mL -1 (R 2 ≥0.999) with 0.069-0.365 μg·mL -1 LOD, and 0.171-1.106 μg·mL -1 LOQ, with good system suitability (<2 % RSD of retention time, peak area, and tailing factor, 6,000-1,336,000 N, and >1.5 peak resolution), <10 % RSD of precision, stability, repeatability, and robustness, and 99.2 - 105.0 % of recovery. The applicability of this method was demonstrated by the determination of polyphenols in nine cultivars of tomatoes. The results showed that '184' possessed the highest content of total polyphenols (1249.53 μg·g -1 DW) followed by 'Disease resistance 184' (1064.93 μg·g -1 DW). The main polyphenol components were rutin, quercetin, gallic acid, chlorogenic acid, 2,5-dihydroxy benzoic acid, caffeic acid and benzoic acid in tomato fruits. In conclusion, this novel HPLC method is useful and acceptable to analyze polyphenols in tomato fruit., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024. Published by Elsevier B.V.)

The pharmaceutical industry is rapidly advancing toward new drug modalities, necessitating the development of advanced analytical strategies for effective, meaningful, and reliable assays. Hydrophilic Interaction Chromatography (HILIC) is a powerful technique for the analysis of polar analytes. Despite being a well-established technique, HILIC method development can be laborious owing to the multiple factors that affect the separation mechanism, such as the selection of stationary phase chemistry, mobile phase eluents, and optimization of column equilibration time. Herein, we introduce a new automated multicolumn and multi-eluent screening workflow that streamlines the development of new HILIC assays, circumventing the existing tedious 'hit-or-miss' approach. A total of 12 complementary columns packed with sub-2 µm fully porous and 2.7 µm superficially porous particles operated on readily available ultra-high pressure liquid chromatography (UHPLC) instrumentation across a diverse set of commercially available polar stationary phases were investigated. Different mobile phases with pH ranging from pH 3 to 9 were evaluated using different organic modifiers. The gradient and column re-equilibration were judiciously set to ensure a reliable assay screening framework that indicates promising conditions for subsequent method optimization to achieve resolution of challenging mixtures. This UHPLC screening system is coupled with a diode array and charged aerosol detectors (DAD, CAD and mass spectrometry) to ensure versatile detection for a variety of compounds. This fast-screening platform lays the foundation for a convenient generic workflow, accelerating the pace of HILIC method development and transfer across both academic and industrial sectors., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

This work describes the development of a new automated parallel dispersive tip microextraction method (Au-Pa-DPX) for the determination of eleven polycyclic aromatic hydrocarbons (PAHs) in four samples of Brazilian sugarcane spirit beverages, with separation and detection done by the HPLC-DAD. The results obtained with the Au-Pa-DPX approach were also compared with those obtained via the conventional parallel manual DPX method with the same samples and optimized extraction process. Desorption solvent and cycles of desorption, cleaning and extraction were optimized using response surface methodology and univariate approaches. For the Au-Pa-DPX method, the coefficient of determination (R 2 ) ranged from 0.9948 to 0.9997. The limits of detection and quantification were all 0.303 μg l -1 and 1.00 μg l -1 , respectively. Interday and intraday precision ranged from 7.6 % to 31.7 % and 0.40 % to 15.8 %, respectively. For the manual parallel DPX method, the interday and intraday precision ranged from 8.2 % to 38.1 % and 5.40 % to 18.7 %, respectively. The relative recovery values obtained with the proposed method ranged from 53.29 to 124.94 %. The enrichment factors ranged from 15.13 to 22.35. The sum of PAH concentrations in the four samples ranged from undetected to 25.58 μg l -1 . These results, when correlated to other methods, highlight the gains in regards to precision obtained with the automated apparatus. Furthermore, when compared to other methods from the literature, it is an interesting green alternative for the determination of these analytes and this sample, with high throughput (4.67 min per sample), low consumption of solvents and samples, generating less waste and reducing health risks to the analyst., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interest or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

This study investigates the impact of 2-methyl imidazolium dihydrogen phosphate (2-MIDHP) on monoclonal antibody (mAb) aggregation during the Protein A purification stage, at a low pH (pH 3.0), and the viral inactivation phase. Size-exclusion high-performance liquid chromatography (SE-HPLC) and dynamic light scattering (DLS) were used to assess the mAb aggregation. Additionally, the influence of 2-MIDHP on mAb recovery, host cell protein (HCP) clearance, and Protein A leaching was investigated. Thermal stability of mAb, eluted in buffers containing 5 % to 25 % 2-MIDHP was analysed, using differential scanning calorimetry (DSC). Structural insights were obtained via circular dichroism (CD) and fluorescence spectroscopy. Our findings indicated that 2-MIDHP exerted a concentration-dependent protective effect against mAb aggregation, at the pH of 3.0. As the concentration of 2-MIDHP was increased from 0 % to 25 %, the aggregation was significantly reduced from 3.8 ± 0.01 % to 0.56 ± 0.002 %, as analysed by SE-HPLC. Addition of 2-MIDHP did not significantly impact the mAb recovery, HCP clearance, or Protein A leaching. DSC data supported these results, with higher 2-MIDHP concentrations leading to increased melting temperatures of mAb. CD and fluorescence spectroscopy revealed no significant changes in the secondary structure or aromatic residue environment in 2-MIDHP-treated samples, despite the observed reduction in aggregation. The results suggested that 2-MIDHP mitigated mAb aggregation during Protein A purification, possibly by stabilizing the protein structure under acidic stress conditions. These findings offer valuable insights for improving the robustness of mAb purification processes, enhancing product quality and yield., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Calcium β‑hydroxy-β-methylbutyrate (CaHMB) can promote muscle growth, prevent muscle atrophy, and enhance immunity, therefore, it is widely used as a nutritional supplement in special medical formula food and sports nutrition food. Many methods for the detection of CaHMB have been reported, but the pretreatment method for these reported literatures directly involves extraction using hydrochloric acid solution, without any purification steps. A method for accurately determining CaHMB in special medical formula food and sports nutrition food was established for the first time using solid-phase extraction (SPE) purification and high-performance liquid chromatography method (HPLC). The samples were extracted and precipitated protein using methanol-water solution, purified using SPE method and analyzed by HPLC on diode array detector (DAD) mode under external standard method. The method obtained excellent calibration linearity (r 2 >0.9993) and a satisfactory analysis of the targeted compound, which were evaluated with calibration standards over the range of 0.020-2.00 mg/mL. The limit of quantifications (LOQs), which defined as the lowest spiking level, were set at 0.4 g/100 g (special medical formula food) and 1.0 g/100 g (sports nutrition food). The average recoveries were within 92.9-104% for the analytes, and the relative standard deviations (RSDs) were below 3.93%, measured at low, medium, and high concentrations. Moreover, the positive sample analysis results indicated that CaHMB was detected on 10 real special medical formula food and sports nutrition food products, the contents of which were generally consistent with their labeled values, with measured values ranging from 97.1 % to 119 % of the labeled values. These results suggested that the developed highly sensitive and specific method is highly feasible for monitoring of the target analyte in special medical formula food and sports nutrition food., Competing Interests: Declaration of competing interest The authors declared that they have no conflicts of interest to this work. We declare that we do not have any commercial or associative interest that represents a conflict of interest in connection with the work submitted., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Anamorelin, a non-peptide ghrelin analog and growth hormone secretagogue, is a novel oral drug used to treat cancer cachexia. Patients with cancer cachexia frequently use several drugs and anamorelin is a substrate of cytochrome P450 (CYP) 3A4; therefore, drug-drug interactions with CYP3A4 inhibitors and inducers pose a clinical problem. In this study, we aimed to determine the concentration of anamorelin in human plasma using a simple high-performance liquid chromatography-ultraviolet (HPLC-UV)-based method. The analysis involved extracting a 200-μL plasma sample and protein precipitation using solid-phase extraction. Anamorelin was isocratically separated using a mobile phase consisting of 0.5% potassium dihydrogen phosphate (pH 4.5) and acetonitrile (61:39, v/v) on a Capcell Pack C18 MG II column (250 mm × 4.6 mm) at a flow rate of 1.0 mL/min and monitored at a detection wavelength of 220 nm. The calibration curve was linear within a plasma concentration range of 12.5-1,500 ng/mL, with a coefficient of determination of 0.9999. The intra- and inter-day coefficients of variation were 0.37-6.71% and 2.05-4.77%, respectively. The accuracy of the assay and recovery were 85.25-112.94% and > 86.58%, respectively. This proposed HPLC-UV method is simple and can be applied in clinical settings.

A green and simple UPLC method was developed and optimized, adopting a factorial design for simultaneous determination of oseltamivir phosphate and remdesivir with dexamethasone as a co-administered drug in human plasma and using daclatasvir dihydrochloride as an internal standard within 5 min. The separation was established on UPLC column BEH C 18 1.7 μm (2.1 × 100.0 mm) connected to UPLC pre-column BEH 1.7 μm (2.1 × 5.0 mm) at 50 °C with an injection volume of 10 μL. The photodiode array detector (PDA) was set at three wavelengths of 220, 315, and 245 nm for oseltamivir phosphate, the internal standard, and both dexamethasone and remdesivir, respectively. The mobile phase consisted of methanol and ammonium acetate solution (40 mM) adjusted to pH 4 in a ratio of 61.5:38.5 (v/v) with a flow rate of 0.25 mL min -1 . The calibration curves were linear over 500.0-5000.0 ng mL -1 for oseltamivir phosphate, over 10.0-500.0 ng mL -1 and 500.0-5000.0 ng mL -1 for dexamethasone, and over 20.0-500 ng mL -1 and 500.0-5000.0 ng mL -1 for remdesivir. The Gibbs free energy and Van't Hoff plots were used to investigate the effect of column oven temperatures on retention times. Fluoride-EDTA anticoagulant showed inhibition activity on the esterase enzyme in plasma. The proposed method was validated according to the M10 ICH, FDA, and EMA's bioanalytical guidelines. According to Eco-score, GAPI, and AGREE criteria, the proposed method was considered acceptable green., (© 2024. The Author(s).)

A selective, precise, and accurate reversed HPLC method has been developed and validated for simultaneous separation and determination of two veterinary drugs, dipyrone and hyoscine, in their combined dosage form in the presence of their official impurities, namely 4-aminoantipyrine and tropic acid, in addition to the formulated preservative: phenol. The linearity range was found to be (1.00-35.00 µg/mL) for dipyrone and (2.50-50.00 µg/mL) for hyoscine. It exhibited a satisfactory linearity regression R (0.9999) for both drugs with LOD 0.22 µg/mL and 0.72 µg/mL and LOQ 0.65 µg/mL and 2.19 µg/mL for dipyrone and hyoscine, respectively. Additionally, the two cited drugs were also determined in the presence of dipyrone active metabolite 4-aminoantipyrine using diclofenac as an internal standard in bovine urine. The linearity range was found to be (15-75 µg/mL) for dipyrone, (2.5-60 µg/mL) for hyoscine, and (2.5-60 µg/mL) for 4-aminoantipyrine with linearity regression R (0.9999-0.9998). The LLOQ (15, 2.5, 2.5 µg/mL), LQC (45, 7.5, 7.5 µg/mL), MQC (55, 25, 25 µg/mL), and HQC (60, 50 50 µg/mL) were determined for dipyrone, hyoscine and 4-aminoantipyrine, respectively. UV detection was carried out at 220 nm. The method was validated according to the ICH guidelines, as well as according to FDA guidelines for determining both drugs in bioanalytical matrices and both proved accuracy and precision. A statistical comparison was made between the results obtained and those obtained by the reported method, showing no significant difference in accuracy and precision at p = 0.05. The suggested method was proved eco-friendly through a greenness assessment using two different tools (The analytical eco-scale scored 83, and the AGREE-Analytical Greenness Metric approach scored 0.83). The suggested method can be used in the routine work of quality control labs, screening for drug abuse, and ensuring clean sport for horse racing., (© 2024. The Author(s).)

Aflatoxins pose a major health concern and require strict monitoring in food products. Existing methods rely on hazardous organic solvents for extraction, prompting the development of a greener alternative. This study explores deep eutectic solvents (DESs) for aflatoxin extraction from pistachios, a valuable food product prone to aflatoxin contamination. The proposed method utilizes DES extraction followed by solid-phase extraction cleanup and ultrahigh-performance liquid chromatography coupled with fluorescence detector analysis. Recovery rates ranged from 85.5 to 99.1% for pistachios spiked with 1-8 ng/g aflatoxins, in compliance with EU regulations, with coefficients of variation less than 2.94%. The method demonstrates good sensitivity with limits of detection and quantification in the range of 0.02-0.22 ng/g and 0.05-0.72 ng/g, respectively. Greenness assessment using AGREEPrep and White Analytical Chemistry metrics confirms its environmental sustainability. This approach offers a promising, safer, and more eco-friendly alternative for aflatoxin extraction from complex food matrices like pistachios.

Advances in the understanding of bioavailability and metabolism of bioactive compounds have been achieved primarily through targeted or semi-targeted metabolomics approaches using the hypothesis of potential metabolized compounds. The recent development of untargeted metabolomics approaches can present great advantages in this field, such as in the discovery of new metabolized compounds or to study the metabolism of compounds from multiple matrices simultaneously. Thus, this study proposes the use of an untargeted metabolomics strategy based on HPLC-ESI-QTOF-MS for the study of bioavailability and metabolism of bioactive compounds from different vegetal sources. Specifically, this study has been applied to plasma samples collected in an acute human intervention study using three matrices ( Hibiscus sabdariffa , Silybum marianum and Theobroma cacao ). This approach allowed the selection of those significant variables associated with exogenous metabolites derived from the consumption of bioactive compounds for their subsequent identification. As a result, 14, 25 and 3 potential metabolites associated with supplement intake were significantly detected in the plasma samples from volunteers who ingested the H. sabdariffa (HS), S. marianum (SM) and T. cacao (TC) extracts. Furthermore, T max values have been computed for each detected compound. The results highlight the potential of untargeted metabolomics for rapid and comprehensive analysis when working with a wide range of exogenous metabolites from different plant sources in biological samples.

Pinocembrin-7-O-β-D-glucoside (PCBG) isolated from Penthorum chinense Pursh was proven to display a wide range of pharmacological effects including hepatoprotection, anti-hepatoma and antifungal activities, etc. The research aims to qualitatively analyze the metabolites of PCBG in rat plasma, urine, bile and feces, and further perform the excretion study of PCBG and its major metabolite pinocembrin (PCB). Fifteen rats were divided into three groups (n=5 for each group) for blood, bile, urine and feces collection, respectively. After PCBG suspension was intragastrically administered to rats at 50 mg/kg, biological samples were collected and processed. The metabolites in each matrix were detected by UHPLC-Q-Exactive-MS/MS. A total of 111 metabolites were observed in plasma, urine, bile and feces, which include hydroxylated, sulfated and glucuronized metabolites, etc. In addition, an UHPLC-MS/MS method was established and applied for the excretion quantification of PCBG and PCB in rat urine, bile, and feces samples. Studies on excretion have shown that PCBG is mainly excreted through feces. The cumulative excretion rates of PCBG and PCB in rat urine, bile and feces were (4.5±2.4)%, (0.2±0.1)% and (18.4±10.5)%, respectively. After hydrolysis by β-glucuronidase/sulfatase, the excretion rates of PCB in urine and bile were (5.7±2.8)% and (8.9±4.2)%. This study contributes to preclinical research on PCBG and explains its pharmacological effects., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

In this experiment, a rapid and highly sensitive ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) technology was established and validated for the quantitation and pharmacokinetic analysis of eupafolin in rat plasma, utilizing licochalcone B as internal standard (IS). After liquid-liquid extraction of the analyte samples by ethyl acetate, chromatographic separation was achieved using a UPLC HSS T3 column under gradient elution conditions, with the mobile phase consisting of acetonitrile and water (with 0.1 % formic acid). Eupafolin was quantified by multiple reaction monitoring (MRM) in electrospray positive-ion mode (ESI+), employing the mass transition m/z 315.2 → 300.3 for eupafolin and m/z 285.4 → 270.3 for IS. Eupafolin demonstrated excellent linear relationship (r > 0.99) over the concentration range of 1.25-1250 ng/mL, with the lower limit of quantification (LLOQ) of the UPLC-MS/MS assay determined as 1.25 ng/mL. Method validation followed the bioanalytical method validation criteria outlined by the FDA. The accuracy of eupafolin ranged from 86.7 % to 111.2 %, and the precision was less than 12 %. The matrix effect was observed at 92.8 %-98.6 %, while the recoveries exceeded 83.2 %. The established UPLC-MS/MS assay was successfully employed for the pharmacokinetic evaluation of eupafolin in rats. The half-lives (t 1/2z ) were determined to be 1.4 ± 0.4 h and 2.5 ± 1.4 h for intravenous and oral administration, respectively. Notably, the bioavailability of eupafolin was relatively low (8.3 %). The optimized UPLC-MS/MS technology showed highly sensitive, selective, and effective, rendering it suitable for the pharmacokinetics of eupafolin in preclinical practice., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Traditional Chinese medicines (TCMs) are popular in clinic because of their safety and efficacy. They contain abundant natural active compounds, which are important sources of new drug discovery. However, how to efficiently identify active compounds from complex ingredients remains a challenge. In this study, a method combining UHPLC-MS/MS characterization and in silico screening was developed to discover compounds with dopamine D2 receptor (D2R) activity in Stephania epigaea (S. epigaea). By combining the compounds identified in S. epigaea by UHPLC-MS/MS with reported compounds, a virtual library of 80 compounds was constructed for in silico screening. Potentially active compounds were chosen based on screening scores and subsequently tested for in vitro activity on a transfected cell line CHO-K1-D2 model using label-free cellular phenotypic assay. Three D2R agonists and five D2R antagonists were identified. (-)-Asimilobine, N-nornuciferine and (-)-roemerine were reported for the first time as D2R agonists, with EC 50 values of 0.35 ± 0.04 μM, 1.37 ± 0.10 μM and 0.82 ± 0.22 μM, respectively. Their target specificity was validated by desensitization and antagonism assay. (-)-Isocorypalmine, (-)-tetrahydropalmatine, (-)-discretine, (+)-corydaline and (-)-roemeroline showed strong antagonistic activity on D2R with IC 50 values of 92 ± 9.9 nM, 1.73 ± 0.13 μM, 0.34 ± 0.02 μM, 2.09 ± 0.22 μM and 0.85 ± 0.08 μM, respectively. Their kinetic binding profiles were characterized using co-stimulation assay and they were both D2R competitive antagonists. We docked these ligands with human D2R crystal structure and analyzed the structure-activity relationship of aporphine-type D2R agonists and protoberberine-type D2R antagonists. These results would help to elucidate the mechanism of action of S. epigaea for its analgesic and sedative efficacy and benefit for D2R drug design. This study demonstrated the potential of integrating UHPLC-MS/MS with in silico and in vitro screening for accelerating the discovery of active compounds from TCMs., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Sphingolipids are a major lipid species found in all eukaryotes. Among structurally complex and diversified lipids, sphingoid bases have been heavily linked to various metabolic diseases. However, most current LC-MS-based methods lack the sensitivity to detect low-abundant sphingoid bases. The 6-Aminoquinolyl-N-hydroxysuccinimidyl carbamate (AQC) derivatization reagent, which efficiently forms covalent bonds with amino groups, has been widely used for amino acid detection. Nevertheless, the commonly used reverse-phase HPLC method for amino acid analysis is not suitable for amphipathic sphingolipids. To address this issue, we report a robust reverse-phase HPLC-MS/MS method capable of separating and detecting hydrophilic amino acids and sphingoid bases in a single run with high sensitivity. This method is also inclusive of other amino metabolites with an expandable target list. We tested this method under various conditions and samples, demonstrating its high reproducibility and sensitivity. Using this approach, we systematically analyzed human serum samples from healthy individuals, dyslipidemia, and type II diabetes mellitus (T2DM) patients, respectively. Two sphingolipids and five amino acids were identified with significant differences between the control and T2DM groups, highlighting the potential of this method in clinical studies., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Hypericum perforatum L. (HPL), also known as St. John's wort, is one of the extensively researched domestically and internationally as a medicinal plant. In this study, non-targeted metabolomics combined with machine learning methods were used to identify reasonable quality indicators for the holistic quality control of HPL. First, the high-resolution MS data from different samples of HPL were collected, and visualized the chemical compounds through the MS molecular network. A total of 122 compounds were identified. Then, the orthogonal partial least squares-discriminant analysis (OPLS-DA) model was established for comparing the differences in metabolite expression between flower, leaf, and branches. A total of 46 differential metabolites were screened out. Subsequently, analyzing the pharmacological activities of these differential metabolites based on protein-protein interaction (PPI) network. A total of 25 compounds associated with 473 gene targets were retrieved. Among them, 13 highly active compounds were selected as potential quality markers, and five compounds were ultimately selected as quality control markers for HPL. Finally, three different classifiers (support vector machine (SVM), random forest (RF), and K-nearest neighbor (KNN)) were used to validate whether the selected quality control markers are qualified. When the feature count is set to 122 and 46, the RF model demonstrates optimal performance. As the number of variables decreases, the performance of the RF model degrades. The KNN model and the SVM model also exhibit a decrease in performance but still manage to satisfy the intended requirements. The strategy can be applied to the quality control of HPL and can provide a reference for the quality control of other herbal medicines., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Since 3D printing technology is an emerging field in pharmaceutical technology, the present study aimed at the development of a mixed-mode liquid chromatographic method for the separation and determination of hydrochlorothiazide, diltiazem, and propranolol to investigate their in-vitro release performance from 3D printed tablets. Due to the unique properties of the mixed-mode stationary phase, the three drugs were separated in less than 8 min under isocratic elution. Method development was accomplished following the Analytical Quality by Design principles and was evaluated using risk assessment and multivariate analysis. The influences of critical method parameters on critical method attributes (were screened using a 2-level fractional factorial design and subsequently optimized through a central composite design. The method operable design region was approved by the establishment of a robust zone using Monte Carlo simulation and capability analysis. The validation of the HPLC method was performed based on the total error concept. The relative bias was varied between ─ 11.6 % and 10.5 % and the RSD values for repeatability and intermediate precision were below 4.4 % in all cases. The limits of detection (LOD) ranged between 0.17 - 0.90 μg/mL and were adequate for the specific application. The developed method was successfully applied to the analysis of the studied drugs in in-vitro drug release samples obtained from 3D-printed tablets combining the above-mentioned active pharmaceutical ingredients (APIs)., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The diabecon is an ayurvedic herbal formulation that contains a mixture of herbs traditionally used as antidiabetic which is reported in the ayurvedic pharmacopeia of India and Indian Materia medica. The diabetic population has a common co-morbidity of hypertension for which losartan drug is commonly used for the treatment of hypertension. However, there is a lack of research on the pharmacokinetics interaction between diabecon and losartan. This research aims to investigate the influence of diabecon on the pharmacokinetics of losartan drugs in rats by establishing a highly sensitive ultra-high performance liquid chromatography-tandem triple quadrupole mass spectrometry (UHPLC-MS/MS) method. The method was validated according to the USFDA guidelines and was applied for the pharmacokinetic study. The lowest concentration of losartan detection in rat plasma was found to be 1 ng/mL and the accuracy and precision were within the linear range (1-1500 ng/mL). The results revealed that after 28 days of dosing diabecon, it has altered the pharmacokinetic parameters like area under the curve (AUC 0-t ), drug clearance (Cl/F), and rate of elimination (Ke) of losartan, which may happen due to enzyme induction. Although there was a change in the pharmacokinetic parameters of losartan when administered in the presence of diabecon, it was found to be nonsignificant in rats (p > 0.05). According to the best of our knowledge, this is the first article that discusses the pharmacokinetic herb-drug interaction between diabecon and losartan., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Aderamastat (FP-025) is a small molecule, selective matrix metalloproteinase (MMP)-12 inhibitor, under development for respiratory conditions which may include chronic inflammatory airway diseases and pulmonary fibrosis. To support evaluation of the pharmacokinetic parameters of Aderamastat in humans, we developed and validated a high-performance liquid chromatography tandem mass spectrometry (LC-MS/MS) analytical method for the quantification of Aderamastat in human plasma. This assay was validated in compliance with the Food and Drug Administration (FDA) Good Laboratory Practice Regulations (GLP) and European Medicines Agency (EMA) guidelines. K 2 EDTA human plasma samples were spiked with internal standard, processed by liquid-liquid extraction, and analyzed using reversed-phase HPLC with Turbo Ion Spray® MS/MS detection. Separation was done using a chromatographic gradient on 5 µm C6-Phenyl 110 Å, 50*2 mm analytical column at a temperature of 35 °C. The LC-MS/MS bioanalytical method, developed by QPS Taiwan to determine the concentration of Aderamastat in K 2 EDTA human plasma, was successfully validated with respect to linearity, sensitivity, accuracy, precision, dilution, selectivity, hemolyzed plasma, lipemic plasma, batch size, recovery, matrix effect, and carry-over. These data indicate that the method for determination of Aderamastat concentrations in human K 2 EDTA plasma can be used in pharmacokinetics studies and subsequent clinical trials with Aderamastat. Authors declare that, this novel data is not published and not under consideration for publication by another journal than this journal. All data will be made available on request., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Inherited disorders of monoamine neurotransmitters are a subset of inborn errors of metabolism affecting biochemical pathways of catecholamines, serotonin or their enzymatic cofactors. Usually, their clinical presentation is similar to those of other common neurological syndromes. For this reason, they are frequently under-recognized and misdiagnosed. Because cerebrospinal fluid concentration of catecholamine metabolites (3-orthomethyldopa and homovanillic acid) and serotonin metabolites (5-hydroxytryptophan and 5-hydroxyindolacetic acid) presents a direct correlation with their brain levels, analysis of this group of compounds is critical to reach an accurate diagnosis. Although there are several published liquid chromatography-based bioanalytical methods for the quantification of these compounds, most of them present disadvantages, making their application difficult to implement in routine clinical practice. In this study, a rapid and simple UHPLC-MS/MS method for simultaneous quantification of 3-orthomethyldopa, 5-hydroxytryptophan, 5-hydroxyindolacetic acid and homovanillic acid in human cerebrospinal fluid was validated. All the evaluated performance parameters, including linearity, carryover, accuracy and precision (within and between-day), lower limit of quantitation, recovery, matrix effect and stability under different conditions met the acceptance criteria from international guidelines. Additionally, 10 human cerebrospinal fluid samples collected via lumbar puncture from 10 pediatric patients were quantified using the validated method to assess its clinical application and diagnostic utility for inherited monoamine neurotransmitter metabolism., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Polycyclic aromatic hydrocarbons (PAHs) are persistent organic pollutants of great concern due to their carcinogenicity and mutagenicity. Their determination in human serum, particularly in at-risk populations, is necessary but difficult because they are distributed over a wide range of polarity and are present at trace level. A new method combining salting-out assisted liquid-liquid extraction (SALLE) and dispersive liquid-liquid microextraction with solidification of floating organic drop (DLLME-SFO) adapted to a reduced volume of sample (100 µl) was developed to determine 24 PAHs in human serum. Some key parameters of DLLME-SFO (volume of extraction solvent, ratio of extraction/dispersive solvent volumes, and salt addition) were first studied by applying it to spiked pure water. For its application to serum, a sample treatment step involving SALLE was optimized in terms of nature and content of salts and applied upstream of DLLME-SFO. It was applied to the extraction of 24 regulated PAHs from spiked serum followed by an analysis by liquid chromatography coupled with UV and fluorescence detection. The extraction recoveries ranged from 48.2 and 116.0 % (relative standard deviations: 2.0-14.6 %, n=5-9), leading to limits of quantification of PAHs in human serum from 0.04 to 1.03 µg/L using fluorescence detection and from 10 to 40 µg/L using UV detection. This final method combining SALLE and DLLME-SFO showed numerous advantages such as no evaporation step, high efficiency and low solvent-consumption and will be useful for monitoring PAHs in low volumes of serum., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper, (Copyright © 2024 Elsevier B.V. All rights reserved.)

Anemarrhena asphodeloides Bunge-Phellodendron chinense Schneid (AAPC) is one of the most widely accepted herb pairs in Chinese medicine prescription for treating benign prostatic hyperplasia (BPH). However, the mechanisms underlying the combination of the two herbs for anti-BPH are still not completely clear. To uncover the potential mechanism of the AAPC herb pair in the treatment of BPH, chemical profiling, network pharmacology, serum metabonomics and experimental validation were integrated. UHPLC-Q-Exactive Orbitrap-MS was performed to characterize the chemical profiling of the herb pair extract, and network pharmacology was employed to forecast the potential effective components, core targets and key signaling pathways. Then, western blot and RT-PCR experiments were conducted to verify the PI3K/Akt/NF-κB signaling pathway predicted by network pharmacology. Finally, the serum differential metabolites and metabolic pathways were analyzed by serum non-targeted metabonomics, and these results were jointly analyzed by MetScape. 51 chemical components of the AAPC herb pair extract were identified, including phellodendrine, magnoflorine, berberine, mangiferin, anemarsaponin BIII, etc. In network pharmacology, the predicted core targets of these components include AKT1, TNF, EGFR, PTGS2, PIK3CA, etc. The KEGG pathway enrichment analysis indicated that PI3K-Akt, Rap1 and MAPK signaling pathways may play a key role in the AAPC herb pair for the treatment of BPH, and the results of animal experiments demonstrated that the herb pair could significantly inhibit the activation and expression of p-PI3K/PI3K, p-Akt/Akt, p-NF-κB/NF-κB in protein and mRNA levels. Furthermore, 31 serum differential metabolites and three main metabolic pathways were obtained by serum non-targeted metabonomics. And the crucial metabolic pathway of arachidonic acid (AA) was obtained by integrated analysis of network pharmacology and metabonomics results. In conclusion, the AAPC herb pair can improve BPH through inhibiting the activation and expression of the PI3K/Akt/NF-κB signaling pathway and AA metabolism., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Cabergoline is a dopamine agonist with applications as anti-Parkinson drug and prolactin inhibitor. The cabergoline drug product Laktostop® 50 µg/mL is used in veterinary medicine for lactation suppression in cats and dogs e.g. during false pregnancy. Recently, during ongoing HPLC stability testing of Laktostop® 50 µg/mL a new oxidation product of Cabergoline was identified. A synthesis starting from Cabergoline was developed, followed by full characterization of the unknown impurity. Preliminary HPLC and LC-MS analyses indicated the unknown impurity as mono-oxygenated product of Cabergoline (Cabergoline N-oxide) that is presumably formed with oxygen by a radical mechanism. Thus, Cabergoline was treated with oxidizing agents such as m-chloroperoxybenzoic acid to afford the desired Cabergoline-N-oxide as a byproduct. After isolation by column chromatography, NMR and LC-MS-MS studies provided evidence that oxidation occurred at the N-allyl nitrogen of Cabergoline to form Cabergoline-N-oxide. © 1905 Elsevier Science. All rights reserved., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships: T. Lechel, R. Silva Otero, A. Rutkowski, D. Matzkow, J. Zart and T. Hartmann are employed at Chemisch-pharmazeutisches Labor, Rolf Sachse GmbH (CPL). D. Hochhuth is employed at CP-Pharma Handelsgesellschaft mbH which financed the project. However, no one at CPL or CP-Pharma had an influence on the results presented in the manuscript. A. Springer collaborated with CPL for LC-MS analysis of cabergoline N-oxide 5. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Germacrone and curdione are germacrane-type sesquiterpenoids that are widely distributed and have extensive pharmacological activities; they are the main constituents of 'Xing-Nao-Jing Injection' (XNJ). Studies on the metabolic features of germacrane-type sesquiterpenoids are limited. In this study, the metabolites of germacrone and curdione were characterized by UHPLC-Q-Exactive Oribitrap mass spectrometry after they were orally administered to rats. In total, 60 and 76 metabolites were found and preliminarily identified in rats administered germacrone and curdione, respectively, among which at least 123 potential new compounds were included. New metabolic reactions of germacrane-type sesquiterpenoids were identified, which included oxidation (+4 O and +5 O), ethylation, methyl-sulfinylation, vitamin C conjugation, and cysteine conjugation reactions. Among the 136 metabolites (including 113 oxidation metabolites, two glucuronidation, two methylation, nine methyl-sulfinylation, three ethylation, six cysteine conjugation, and one Vitamin C conjugation metabolites), 32 metabolites were detected in nine organs, and the stomach, intestine, liver, kidneys, and small intestine were the main organs for the distribution of these metabolites. All 136 metabolites were detected in urine and 64 of them were found in feces. The results of this study not only contribute to research on in vivo processes related to germacrane-type sesquiterpenoids but also provide a strong foundation for a better understanding of in vivo processes and the effective forms of germacrone, curdione, and XNJ., Competing Interests: Declaration of Competing Interest We have no conflicts of interest to disclose., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Phytic acid or inositol hexakisphosphate (InsP 6 ) and its dephosphorylated forms (InsP 5 , InsP 4 & InsP 3 ) are integral to cellular functions and confer several health benefits. The present study was aimed to develop a cost effective and high sample throughput RP-HPLC-RID method for routine quantification of lower inositol phosphates in both raw and processed cereals and pulses. For this asuitable mobile phase composition was formulated and two columns (MacroporusHamilton PRP-1 Vs Waters Symmetry C18) were compared in terms ofsystem specificity,linearity, accuracy and precision. Separation ofInsP 3 , InsP 4 , InsP 5 and InsP 6 were recorded at 2.39, 2.93, 3.83 and 5.37 min usingPRP-1column while the RT were 4.67, 5.64, 6.99 and 9.14 min with C18column.Linearity of standards (R 2  > 0.99), with an accuracy and precision ranging from 1 to 5 % was achieved. The LOD and LOQ of all InsPs were 5 and 15 μg/ml, respectively. In quality control sample InsP 6 was found in highest concentration (446 ± 14.71 mg/100 g) followed by InsP 5 (162 ± 8.00 mg/100 g) and InsP 4 with the least concentration of 11.63 ± 1.06 mg/100 g whereas InsP 3 was below detectable limit (BDL). The optimised method was used for profiling of InsPs in the raw and processed cereals and pulses consumed as staple foods in India. Processed foods contained lesser InsP 6 and more of lower InsP compared to raw foods. The optimised method using unique mobile phase composition was found to yield accurate results and can used for large scale analysis of cereals and pulses and estimation of mineral nutrition potential and allied health benefits., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Piper colubrinum Link. is an underexplored crop regarding its metabolites and therapeutic attributes. Current study aimed to identify the possible volatile and non-volatile metabolites of P. colubrinum fruit and studied its metabolite diversity with medicinally valued Piper species viz. P. nigrum L., P. longum L. and P. chaba Hunter. The volatile constituents of P. colubrinum essential oil by GC-MS revealed the presence of sesquiterpenes as the major contribution. The sesquiterpenes α-muurolol (12.5 %) and β-caryophyllene (11.3 %) were the predominant volatile components. Few aliphatic compounds like n-heptadecane and trace amounts of monoterpenes (α- and β-pinene and α-terpineol) were also identified from this crop. The fatty acid profiling by GC-MS revealed mainly oleic acid (41.3 %) followed by palmitic and linoleic acids. HPLC analysis demonstrated that the major pungent alkaloid piperine was found to be trace (0.04 %) in P. colubrinum. The LC-QTOF-MS/MS profiling of the chloroform extract of the P. colubrinum revealed the presence of non-volatile constituents including phenolic and alkaloid compounds. Ferulic acid, rosmarinic acid, salicylic acid, kaempferol-5-glucoside, 5-methoxysalicylic acid, apigenin-7-galactoside, kaempferide-3-glucoside, luteolin, kaempferol, apigenin and scutellarein-4'-methyl ether were the phenolic compounds whereas piperlonguminine was the alkaloid compound identified. Finally, the biochemical parameters of this crop were compared with that of P. nigrum, P. longum and P. chaba and average linkage cluster dendrogram revealed that P. colubrinum was biochemically distinct from other three Piper species., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Citri Reticulatae Pericarpium (CRP) is used as common health-care food and traditional Chinese medicine (TCM), which exerts pharmacological effects, such as anti-cardiovascular, anti-tumor, anti-oxidant, anti-inflammatory, anti-virus, hepatoprotective, blood pressure-lowering and neuroprotective. In this study, reliable, and sensitive ultra-high performance liquid chromatography/tandem mass spectrometry (UPLC-MS/MS) and gas chromatography-mass spectrometry (GC-MS) methods were developed and validated for the determination of eleven active components in rat plasma after oral administration of the CRP extract. The results of this method exhibited that the specificity, linearity (r > 0.999), precision and accuracy (the coefficient of variation (CV) < 11.5 %), recovery (52.9-107.9 %), matrix effects (63.8-107.5 %), and stability (CV < 10.8 %) met all requirements for the quantitation of plasma samples. The pharmacokinetic results showed that the T max of flavone glycosides was less than 0.7 h, and that of polymethoxyflavones and volatile components were within 1-7 h. Meanwhile, the area-under-the-curve (AUC) and concentration maximum (C max ) of hesperidin, nobiletin, tangeretin, and D-limonene were higher than those of the other components, suggesting that the plasma exposure levels of these constituents were higher in CRP. The present research lays a foundation for elucidating the therapeutic material basis and provides a reference for further scientific research and clinical application of CRP., Competing Interests: Declaration of Competing Interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The present work describes a developed analytical method based on a colorimetric assay using gold nanoparticles (AuNPs) along with chemometric techniques for the simultaneous estimation of sofosbuvir (SOF) and ledipasvir (LED) in their synthetic mixtures and tablet dosage form. The applied chemometric approaches were continuous wavelet transform (CWT) and least squares support vector machine (LS-SVM). Characterization of AuNPs and AuNPs in combination with the drug was performed by UV-vis spectrophotometer, transmission electron microscopy (TEM), dynamic light scattering (DLS), and Fourier transform infrared (FTIR) spectroscopy. In the CWT method, the zero amplitudes were determined at 427 nm with Daubechies wavelet family for SOF (zero crossing point of LED) and 440 nm with Symlet wavelet family for LED (zero crossing point of SOF) over the concentration range of 7.5-90.0 μg/L and 40.0-100.0 μg/L with coefficients of determination (R 2 ) of 0.9974 and 0.9907 for SOF and LED, respectively. The limit of detection (LOD) and limit of quantification (LOQ) of this method were found to be 7.92, 9.96 μg/L and 12.02, 30.2 μg/L for SOF and LED, respectively. In the LS-SVM model, the mean percentage recovery of SOF and LED in synthetic mixtures was 98.29 % and 99.25 % with root mean square error of 2.392 and 1.034, which were obtained by the optimization of regularization parameter (γ) and width of the function (σ) based on the cross-validation method. The proposed methods were also applied for the determination concentration of SOF and LED in the combined dosage form, recoveries were higher than 95 %, and relative standard deviation (RSD) values were lower than 0.4 %. The achieved results were statistically compared with those obtained from the high-performance liquid chromatography (HPLC) technique for the concurrent estimation of components through one-way analysis of variance (ANOVA), and no significant difference was found between the suggested approaches and the reference one. According to these results, simplicity, high speed, lack of time-consuming process, and cost savings are considerable benefits of colorimetry along with chemometrics methods compared to other ways., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

A method of analysis was developed for the simultaneous chemo- and enantioseparation of 2-, 3-, and 4-chloromethcathinones by high-performance liquid chromatography tandem mass-spectrometry. The fast method enables the reliable identification of positional isomers of chloromethcathinones in biological samples. In addition, the same method can be used for the enantioselective quantitative determination of one of these compounds and its major phase-1 metabolites in biological fluids. The developed method was applied to oral fluid samples collected by police during routine random traffic control in Belgium from January to November, 2023. It was found that 3-CMC was more frequently abused compared to 4-CMC. Although some differences were observed between the concentrations of enantiomers in OF, most likely the drugs were abused in the racemic form. No abuse of 2-CMC was detected at the timepoint of sample collection., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Surveillance testing is an essential component to ensuring safe, effective, and high-quality drug products are available in the commercially marketed US supply chain. Surveillance allows the agency to assess product quality and monitor for potential adulteration of drug products being used by consumers. Opioid drug products can be adulterated to enhance the effect of the intended active ingredient. Numerous accounts have been reported where fentanyl has been used as an adulterant in illicit street drugs such as heroin, cocaine, or methamphetamine. To efficiently surveil the legitimate opioid supply chain, an analytical method with the ability to simultaneously detect, identify and quantify opioid molecules is desired. In this study, a multi-opioid protocol (MOP) using liquid chromatography-high resolution mass spectrometry (HPLC-HRMS) technology was developed and validated for the detection and quantification of 27 opioid drugs. The MOP analytical procedure was applied to the analysis of drug substance and finished dosage forms. MOP was used to identify and quantify active pharmaceutical ingredients (API) listed on the label claim, and in the case of suspected economically motivated adulteration could identify and quantify undeclared opioid APIs. The analytical method analysis time was 16 minutes and the LOD and LOQ in full MS mode were (average) 0.3 and 0.8 ng/mL, respectively. The validation criteria parameters were satisfactory based on international guidelines (ICH). The MOP was successfully applied to the analysis of over 160 drug substances and finished products. For all samples tested in the study, their identities were confirmed, and assays met specifications. Overall, there was no evidence of illegal substitution or adulteration in any of the ingredients and products tested from the legitimate commercial marketed US supply chain., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Published by Elsevier B.V.)

Taking advantage of the competitive binding affinity towards Ti(IV) between 4-(2-pyridylazo) resorcinol (PAR) and phthalate, a simple indicator displacement (ID)-based colorimetric assay was designed for indirect determination of a well-known phthalic acid ester, dibutyl phthalate (DBP). The indicator PAR and Ti(IV) formed a purplish-red-colored Ti(IV)-PAR complex (λ max = 540 nm) at a 1:1 ratio. In the presence of pre-hydrolyzed DBP, colorless complex formation of phthalate ion (emerging from alkaline hydrolysis of DBP) with Ti(IV) resulted in a hypsochromic shift in absorbance maximum, accompanying a color change from purplish-red to yellowish-orange (λ max = 390 nm) by the release of PAR from Ti(IV)-PAR system. Based on this mechanism, the linear response range of the system for DBP was found to lie between 0.16 and 0.37 mmol L -1 with an experimental detection limit of 11.6 µmol L -1 . The recommended Ti(IV)-PAR system was successfully applied to DBP-containing pharmaceutical products (as real sample) after a simple clean-up process for removing possible water-soluble interferents. The analytical results obtained from the recommended method (by applying the standard addition approach) and the reference liquid chromatography-tandem mass spectrometric (LC-MS/MS) method were statistically compared using DBP-extract of the drug samples. Consequently, a simple and selective colorimetric ID strategy was proposed for the analysis of DBP in pharmaceuticals for the first time., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper, (Copyright © 2024 Elsevier B.V. All rights reserved.)

The Liangfu formula, as described in 'Liangfang Jiye', is well-known for its efficacy in treating stomach pain, abdominal pain, and dysmenorrhea. This research aimed to investigate the pharmacokinetics and tissue distribution of 5-hydroxy-7-(4-hydroxy-3-methoxyphenyl)-1-phenyl-3-heptanone (DPHA), Galangin, Kaempferide, 5-Hydroxy-1,7-diphenyl-3-heptanone (DPHC), α-Cyperone, and Nootkatone in vivo using an LC-MS/MS method. The method successfully separated the six active components and internal standards (Chrysin and Yakuchinone-A) on an XB-C18 column with a mobile phase of 0.2 ‰ formic acid water-acetonitrile. It demonstrated good linearity with a correlation coefficient (r 2 ) ≥ 0.9911 and a lower limit of quantification (LLOQ) of 5-80 ng/mL for the different components. Precision, accuracy, matrix effects, and recovery rates were within acceptable ranges. Pharmacokinetic analysis revealed significant differences in parameters between primary dysmenorrhea (PD) and normal rats (especially AUC, T max, and CL z /F). Tissue distribution showed that the six active components of the herbal pair Alpinia officinarum Hance-Cyperus rotundus L. (HPAC) extract was primarily distributed in the liver, lung, and kidney. This study offers valuable insights into the potential mechanisms of action and drug development for treating PD., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Ethnopharmacological Relevance: In traditional Chinese medicine (TCM), Yigong San (YGS) is mainly used to treat dyspepsia caused by deficiency of spleen and stomach qi. Although the chemical composition and bioactivity of YGS has been well studied, the main in vivo compounds and their distribution in tissues still need to be made clearer., Aim of the Study: To elucidate the pharmacokinetic profiles and tissue distribution of eight main compounds of YGS in rats, and provide a reference for clinical application and new drug development., Materials and Methods: UPLC-Q-Exactive-Orbitrap-MS was used to qualitatively characterize the parent compounds and their metabolites in the plasma of rats after oral administration of YGS. A sensitive, reliable, and accurate ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method using UPLC-AB Sciex QTRAP 5500 MS was established to quantitatively determine eight main compounds of YGS in rat plasma and tissues, including liquiritin, isoliquiritin, hesperidin, ginsenosides Rb 1 , Re and Rg 1 , atractylenolides I and II., Results: The mean area under the concentration-time curve (AUC) values of ginsenoside Rb 1 , hesperidin, and liquiritin at low, medium, and high doses were greater than 150 ng h/mL. The elimination half-life (t 1/2 ) values of ginsenoside Rb 1 , atractylenolides I and II (low and medium doses) were longer than 10 h. Peak time (T max ) values of all compounds were shorter than 10 h. Except for atractylenolides, the maximum concentration (C max ) values of the compounds were greater than 10 ng/mL. The eight compounds were detected in the heart, brain, liver, spleen and kidney at 0.25 h after oral administration. Liquiritin and isoliquiritin had higher exposure in the liver and heart. Hesperidin and ginsenosides Rb 1 , Re, and Rg 1 are mainly distributed in the spleen and kidney. Atractylenolides I and II are mainly distributed in spleen, liver and kidney., Conclusions: All main compounds of YGS, i.e., liquiritin, isoliquiritin, hesperidin, ginsenosides Rb 1 , Re, and Rg 1 , and atractylenolides I and II are absorbed into plasma and widely distributed in various tissues. Among them, hesperidin, ginsenoside Rb 1 , and atractylenolide I are main in vivo compounds. They are mainly distributed in spleen, liver and kidney. The results of this study provide a basis for further in-depth development and application of YGS., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Antibiotic-associated diarrhea (AAD) is a common side effect of antibiotic therapy, characterized by intestinal inflammation which reduces the quality of life of patients. Xianglian Pill (XLP) has long been used to treat abdominal pain, diarrhea, bacillary dysentery and enteritis. Studies found that XLP has curative effect on AAD; however, the chemical constituents and mechanism of XLP have not been fully elucidated because of the lack of in vitro and in vivo studies. In this study, ultra-high performance liquid chromatography mass spectrometry method (UPLC-Q-Exactive-Orbitrap-HRMS) was used to examine the components of the XLP. Then, the binding between active compounds and the key targets was studied using network pharmacology and molecular docking. A comparative tissue distribution study was established for the simultaneous determination of the 10 active components in healthy and AAD mouse models. Forty-six components were characterized from XLP. According to the network pharmacology degree value, a prediction was made that encompassed 42 components and 14 core targets, which were intricately involved in crucial biological pathways, such as the AGE-RAGE signaling, cellular senescence, and MAPK signaling. Tissue distribution analysis showed that the 10 components were widely distributed in the heart, liver, spleen, lungs, kidneys, small intestine, and large intestine of mice, with varying concentrations in healthy and AAD mice. Molecular docking analysis also indicated that the active compounds in the tissue distribution could bind tightly to key targets of network pharmacological studies. This study provides a reference for further investigations of the relationships between the chemical components and pharmacological activities of XLP., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. No conflict of interest exits in the submission of this manuscript, and manuscript is approved by all authors for publication. I would like to declare onbehalf of my co-authors that the work described was original research that has not been published previously, and not under consideration for publication elsewhere, in whole or inpart. All the authors listed have approved the manuscript that is enclosed., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Acetaminophen (APAP), or paracetamol, is one of the most widespread and commonly used non-prescription pain medication in the world, and is effective at managing wide range of pain, including headache, muscle ache, and minor arthritic pain. While the pharmacokinetics of APAP is generally understood, there is a lack of data for its transfer ratio especially into the knee. A novel multi-microdialysis model was developed to simultaneously sample from blood, forelimb extensor muscle, brain striatum, and the knee joint cavity in the same experimental subject to investigate the potential interaction between APAP and Achyranthes bidentata Blume (A. bidentata), another widely used traditional Chinese medicininal herb especially for pain in the lower extremity. Rats were pre-treated with A. bidentata extract (ABex), APAP was then administered (60 mg/kg, i.v.), dialysates then subsequently analyzed using HPLC-PDA. Our analysis demonstrated that APAP concentrations, achieved after its administration either alone or in combination with ABex (1 and 3 g/kg, q.d. gavage), could be modelled effectively with a one-compartment model. The distribution ratio (AUC organ /AUC blood ) of blood-to-muscle, blood-to-brain and blood-to-knee was 0.372 ± 0.053, 0.277 ± 0.095 and 0.191 ± 0.042, respectively after administration of APAP (60 mg/kg, i.v.). No significant difference was observed between the pharmacokinetics of APAP administered alone and in combination with ABex; and APAP concentration exceed the half maximal effective concentration (EC 50 ) in all sampled organs for close to 3 hours with one single dose of drug administration, providing evidence for its broad-range analgesic effect., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Liquid-phase microextraction (LPME) possesses a high potential to isolate organic substances from different sample matrices. In this work, LPME was applied for the first time to investigate the biodistribution of diphenidol in different biofluids, organs, and brain regions using a fatal poisoning case. Since the LPME of diphenidol hasn't been reported, the effect of supported liquid membrane (SLM), acceptor and donor phases, and extraction time on LPME performance was investigated first. The solvents of 2-nonanone and 2-nitrophenyl octyl ether (NPOE) were found to be stable and efficient SLMs for LPME of diphenidol from biofluids and tissue samples, respectively. At steady state, the LPME recoveries for different sample matrices were in the range of 87 %-91 %. Due to the clean-up capability of LPME and the relatively high concentration of diphenidol in the fatal poisoning case, the proposed LPME systems were validated with related sample matrices using HPLC-UV for the determination. The methods displayed good linearity (R² ≥ 0.9943), and the limits of detection were 0.30 mg L -1 , 0.28 mg L -1, and 2.7 μg g -1 for blood, urine, and liver samples, respectively. Meanwhile, the precision (≤13%), accuracy (90-110%), and matrices effect (±15%) were satisfactory at low, medium, and high concentrations. In addition, the stability, carryover, and dilution integrity met the requirements of ASB Standard 036. Finally, the proposed method was successfully applied to evaluate the biodistribution of diphenidol in five different biofluids, five organs, and six brain regions from a fatal poisoning case. Generally, the distribution of diphenidol in biofluids was lower than that in the organs and brain regions, and the highest concentration of diphenidol was observed in the liver, which is very important for the selection of inspection samples in forensic toxicological analysis. Therefore, LPME was proved to be a powerful tool for the investigation of biodistribution and postmortem redistribution in the fields of forensics., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Macrocycles play vital roles in supramolecular chemistry and chromatography. 1,1'-Bi-2-naphthol (BINOL)-based chiral polyimine macrocycles are an emerging class of chiral macrocycles that can be constructed by one-step aldehyde-amine condensation of BINOL derivatives with other building blocks. These macrocycles exhibit good characteristics, such as facile preparation, rigid cyclic structures, multiple chiral centers, and defined molecular cavities, that make them good candidates as new chiral recognition materials for chromatographic enantioseparations. In this study, a BINOL-based [2+2] chiral polyimine macrocycle was synthesized by one-step condensation of enantiopure (S)-2,2'-dihydroxy-[1,1'-binaphthalene]-3,3'-dicarboxaldehyde with (1R,2R)-1,2-diaminocyclohexane. The product was modified with 5-bromo-1-pentene and then attached to thiolated silica using click chemistry to construct a new chiral stationary phase (CSP). The enantioselectivity of the new CSP was explored by separating various racemates under normal phase (NP) and reversed phase (RP) high performance liquid chromatography (HPLC). Thirteen racemates and eight racemates were enantioseparated under the two separation modes, respectively, including chiral alcohols, phenols, esters, ketones, amines, and organic acids. Among them, nine racemates achieved baseline separation under NP-HPLC and seven racemates achieved baseline separation under RP-HPLC. High resolution separation was observed with benzoin (Rs = 5.10), epinephrine (Rs = 4.98), 3-benzyloxy-1,2-propanediol (Rs = 4.42), and 4,4'-dimethylbenzoin (Rs = 4.52) in NP-HPLC, and with 4-methylbenzhydrol (Rs = 4.72), benzoin ethyl ether (Rs = 3.79), 1-phenyl-1-pentanol (Rs = 3.68), and 1-(3-bromophenyl)ethanol (Rs = 3.60) in RP-HPLC. Interestingly, the CSP complemented Chiralcel OD-H, Chiralpak AD-H, and CYCLOBOND I 2000 RSP columns for resolution of these test racemates, separating several racemic compounds that could not be well separated by the three commercially available columns. The influences of injected sample amount on separation were also evaluated. It was found that the column exhibited excellent stability and reproducibility after hundreds of injections, and the relative standard deviations (n = 5) of the retention time and resolution were less than 0.49% and 0.69%, respectively. This study indicates that the BINOL-based chiral macrocycle has great potential for HPLC enantioseparation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

A new method for efficiently selecting polypotent natural products is proposed in this study. The method involves using effect-directed HPTLC data and multiobjective optimization algorithms to extract chromatographic signals from HPTLC bioassay images. Three different multiobjective optimization methods, namely Derringer's desirability approach, Technique for order of preference by similarity to ideal solution (TOPSIS), and Sum of ranking differences (SRD), were applied to the chromatographic signals. In combination with jackknife cross-validation, Derringer's approach and TOPSIS demonstrated high similarity in finding the best (most polypotent), next to the best, next to the worst, and worst (least polypotent) extracts, while the SRD resulted in slightly different outcomes. Furthermore, a new method for identifying the chromatographic features that characterize the most polypotent extracts was proposed. This method is based on partial least square regression (PLS) and can be used in combination with HPTLC-chemical fingerprints to predict the desirability of new extracts. The resulting PLS models demonstrated high statistical performance with determination coefficients ranging from R 2 = 0.885 in the case of Derringer's desirability, to 0.986 for TOPSIS. However, the PLS modeling of SRD values was not successful., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Endocannabinoid system, including endocannabinoid neurotransmitters (eCBs), has gained much attention over the last years due to its involvement with the pathophysiology of diseases and the potential use of Cannabis sativa (marijuana). The identification of eCBs and phytocannabinoids in biological samples for forensic, clinical, or therapeutic drug monitoring purposes constitutes a still significant challenge. In this scoping review, the recent advantages, and limitations of the eCBs and phytocannabinoids quantification in biological samples are described. Published studies from 2018-2023 were searched in 8 databases, and after screening and exclusions, the selected 38 articles had their data tabulated, summarized, and analyzed. The main characteristics of the eCBs and phytocannabinoids analyzed and the potential use of each biological sample were described, indicating gaps in the literature that still need to be explored. Well-established and innovative sample preparation protocols, and chromatographic separations, such as GC, HPLC, and UHPLC, are reviewed highlighting their respective advantages, drawbacks, and challenges. Lastly, future approaches, challenges, and tendencies in the quantification analysis of cannabinoids are discussed., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Carolina Henkes Inamassu reports financial support was provided by National Council for Scientific and Technological Development (CNPq). Luisa Raspini e Silva reports financial support was provided by Coordination for the Improvement of Higher Education Personnel (CAPES). If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The adsorption of 11-nor-9-carboxy-∆ 9 -tetrahydrocannabinol (THC-COOH) by the suspended particles in sewage makes it fail to accurately monitor cannabis abuse. In this work, the model sewage sample was prepared through equivalent mixing the sewage from 10 different sewage treatment plants in Guangdong province of China and used as a comprehensive representative for investigating the adsorption and release behavior of THC-COOH on the suspended particles under different temperature and pH. The solid-liquid distribution of THC-COOH in sewage depended strongly on the adsorption and release properties which were susceptible to the temperature and pH, specially adjusting pH to 11.0 could release more than 90 % of THC-COOH from the suspended particles. By means of the kinetics models, pseudo-second-order kinetic and Weber-Morris models revealed the mechanism of adsorption and release of THC-COOH in sewage that was a relatively reversible and controllable process with multiple interactions, and then it was further confirmed by the validation experiment in a variety of actual sewage samples. According to the suggested pH, the modification of the existing detection protocol prior to high performance liquid chromatography-tandem triple quadrupole mass spectrometry (HPLC-TQ-MS/MS), was successfully applied to determination of THC-COOH in the stimulated positive samples, and the recoveries and RSDs were respectively 95.48-99.79 % and 4.0-5.6 %. The finding could greatly help improving the accuracy of not only the detection of THC-COOH in sewage but also the estimation data of the consumption level of cannabis in the related regions., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Metabolites identification is crucial to develop functional foods or perform quality control. Prunella vulgaris (Xia-Ku-Cao) is a medicinal and edible plant used as the herbal medicine or main additive in functional beverage. However, current analytical strategies can only on-line characterize tens of compounds, restricted by insufficient chromatographic resolution and low coverage of the mass spectrometric scan methods. This work was designed to characterize the wide-polarity components from the ear of P. vulgaris. The total extract was fractionated by semi-preparative high-performance liquid chromatography into the retained medium-polarity fraction and unretained polar fraction, which were further analyzed by offline two-dimensional liquid chromatography (2D-LC) and hydrophilic interaction chromatography, respectively. Data-independent high-definition MS E of the Vion™ ion mobility time-of-flight mass spectrometer was utilized enabling the high-coverage acquisition of collision-induced dissociation-MS 2 data. The offline 2D-LC, configuring the XBridge Amide and HSS T3 columns, gave high orthogonality (0.81) and effective peak capacity (1555). Automatic peak annotation facilitated by the UNIFI™ bioinformatics platform and comparison with 62 reference compounds achieved the efficient and more reliable structural elucidation. We could characterize 255 compounds from P. vulgaris, with numerous phenylpropanoid phenolic acids and triterpenoid O-glycosides newly reported. Especially, collision cross section (CCS) prediction and targeted isolation of three compounds assisted in the identification of 39 groups of isomers. Additionally, 17 hydrophilic compounds, involving oligosaccharides and organic acids, were characterized from the unretained polar fraction. Conclusively, the in-depth metabolites identification of P. vulgaris was accomplished, and the results can benefit the development and better quality control of this valuable plant., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The use of pesticides has increased with the development of agriculture. However, due to the trace content and the matrix's inherent complexity in environmental water, development of rapid and sensitive detection method present significant challenges in the analysis of pesticide residues. The study synthesized magnetic graphene oxide (MGO) by combining superparamagnetic nanoparticles with the easy modification of graphene oxide (GO). Covalent organic frameworks (COFs) were then modified to have a large specific surface area. Finally, magnetic graphene oxide-based covalent organic frameworks, namely MGO-COFs, were obtained with a spherical structure and used as magnetic solid-phase extraction materials, which was successfully used to determine the seven pesticide residues in environmental samples in conjunction with high performance liquid chromatography. The method has a wide linear range for the tested pesticides, with satisfactory correlation coefficients (R ≥ 0.099) and low detection limits (0.3-1.21 μg L -1 ). The correlation coefficients for all seven pesticides were high (R 2 ≥ 0.9996). The spiked recoveries, exhibiting a range of 91.3 to 109 %, demonstrated that the developed MGO-COF-MSPE-HPLC-UV method is simple, efficient, and suitable for the analysis and detection of seven pesticide residues in environmental water., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Styrene-maleic acid (SMA) copolymer has received much attention for its excellent solubilization characteristics. In this work, SMA copolymer brush-based chromatographic stationary phases were exploited and developed for the first time. First, SMA copolymer brush was in situ grown on the surface of spherical silica via living/controlled reversible addition-fragmentation chain transfer (RAFT) polymerization method. Subsequently, as a proof-of-concept demonstration, the copolymer was esterified by diethylene glycol mono-2-ethylhexyl ether (DGME) and 2-(2-ethylhexyloxy) ethanol (EHOE), respectively. The obtained Sil-SMA-DGME and Sil-SMA-EHOE copolymer-brush chromatographic stationary phases were characterized by transmission electron microscopy, Fourier transform infrared spectrometer, X-ray photoelectron spectroscopy, and thermogravimetric analysis, respectively. The chromatographic retention mechanism indicated that both the two packed columns exhibited hydrophilic/reverse mixed-mode retention modes. The maximum column efficiency was up to 71,000 N/m. The chromatographic separation performance evaluation indicated that the novel kind of stationary phases had excellent separation capabilities for hydrophilic, hydrophobic compounds and phospholipid standards. In addition, by combination with mass spectrometry identification, the Sil-SMA-DGME column was further exploited for separation and identification of phospholipids in human lung cancer cells. Totally, 9 classes including 186 phospholipid species were successfully identified. The results demonstrated the promising application prospects of the novel kind of SMA copolymer-brush chromatographic stationary phases., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The last few years have seen a rise in the identification and development of bio-therapeutics through the use of cutting-edge delivery methods or bio-formulations, which has created bio-analytical difficulties. Every year, new bio-pharmaceutical product innovations come out, but the analytical development of these products is challenging. Quantifying the products and components of conjugated molecular structures is essential for preclinical and clinical research in order to guide therapeutic development, given their intrinsic complexity. Furthermore, a significant amount of information is needed for the measurement of these unique modalities by LC-MS techniques. Numerous LC-MS based methods have been developed, including AEX-HPLC-MS, RP-IP-LCMS, HILIC-MS, LCHRMS, Microflow-LC-MS, ASMS, Hybrid LBA/LC-MS, and more. However, these methods continue to face problems, prompting the development of alternative approaches. Therefore, developing bio-molecules that are this complicated and, low in concentration requires a skilled LC-MS based approach and knowledgeable personnel. This review covers general novel modalities classifications, sample preparation techniques, current status and bio-analytical strategies for analyzing various novel modalities, including gene bio-therapeutics, oligonucleotides, antibody-drug conjugates, monoclonal antibodies and PROTACs. It also covers how these strategies have been used in the past and how they are being used now to address challenges in the development of LC-MS based methods, as well as improvement strategies, current advancements and recent developed methods. We additionally covered on the benefits and drawbacks of different LC-MS based techniques for the examination of bio-pharmaceutical products and the future perspectives., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)