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Medicinal plants in the high salinity and high alkaline environment might possess some special chemical constituents with new skeleton and high bioactivity. In this work, the main chemical constituents of Limonium sinense, namely flavonoids, were comprehensively studied for the first time. A new flavonoid together with five known compounds were isolated from the whole plants of L. sinense. Their structures were determined by the analysis of comprehensive spectroscopic data. All isolates were evaluated for their anti-inflammatory activity. Compound 1 exhibited moderate anti-inflammatory activity on NO production with IC 50 value of 20.5 ± 1.3 μM. In addition, 38 flavonoids were identified by UPLC-MS/MS method and 18 reported flavonoids were summarised.

Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) such as icotinib, osimertinib, and aumolertinib have emerged as promising treatment options for EGFR mutated Non-small cell lung cancer (NSCLC) patients. Additionally, anlotinib, an anti-angiogenic agent targeting VEGFR, FGFR, and PDGFR, has been used in combination with EGFR-TKIs in NSCLC cases. A method utilizing ultrahigh performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was developed and validated for quantifying icotinib, osimertinib, aumolertinib and anlotinib simultaneously in clinical TDM. The chromatographic separation was performed using a Kinetex C18 column (100 mm × 2.1 mm) and an elution gradient of ammonium acetate in water acidified with 0.1 % formic acid and in acetonitrile. The assay was validated over a linear range of 4-2000 ng/mL for icotinib, 2-1000 ng/mL for osimertinib, 1-500 ng/mL for aumolertinib, and 0.8-400 ng/mL for anlotinib, following the guidelines on bioanalytical methods by FDA. The quantification method exhibited satisfactory performance in terms of selectivity, accuracy (from 91.3 % to 107 %), precision (intra- and inter-day coeffficients of variation ranged from 0.944 % to 7.48 %), linearity, recovery (from 86.0 % to 91.9 %), matrix effect (IS-normalized matrix factors were from 96.7 % to 102 %), and stability. Overall, the method proved to be sensitive, reliable, and straightforward, enabling successful simultaneous determination of blood concentrations of icotinib, osimertinib, aumolertinib, and anlotinib in patients. The validity of the method has been confirmed across various instruments., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Mingxia Wang reports financial support was provided by Projects of Hebei Provincial Natural Science Foundation. Mingxia Wang reports financial support was provided by Hebei Science and Technology Major Project for Biological Medicine Innovation and Development. 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 The Authors. Published by Elsevier B.V. All rights reserved.)

Phytic acid (IP6) and its degradation products lower myo-inositol phosphates exert different impacts on nutrient bioavailability and product quality characteristics. However, information regarding the occurrence of IP6 and its degradation products is scarce. In this work, simultaneous determination of IP6 and its degradation products in soybeans was developed, with emphasis on analysis by UPLC-MS/MS and a BEH Amide column both with hybrid surface technology. The retention and analyte/metal surface interactions issues were effectively addressed without ion-pairing reagents addition or derivatization. This method was applied to analyze soybeans from China. Total contents were 0.44-13.2 mg/g, and IP6 and its degradation product myo-inositol pentakisphosphate (IP5) were the predominant analytes, accounting for over 99%. Accession type significantly affected IP5 content, and landraces had significantly higher IP5 than cultivars. Geographically, the lowest IP6 was concentrated in the Huanghuaihai region. Significant correlations existed between IP6 and longitude, altitude, and annual cumulative sunshine hours. This study provides comprehensive insights into the IP6 and its degradation product profile in soybeans, which will benefit breeding soybeans based on specific requirements., 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 Ltd.)

Pharmaceutical care is important for mental health during the perinatal period, which is often characterized by insomnia. In recent years, prescriptions of melatonin receptor agonists (MRAs) and dual orexin receptor antagonists (DORAs) for insomnia have increased; however, their use during the perinatal period has scarcely been reported. In the present study, we developed a UPLC-MS/MS method for the quantification of ramelteon, its metabolite M-II, suvorexant, and lemborexant in human plasma and breast milk to accumulate information on the safety and transfer of MRAs and DORAs into breast milk. Samples of MRAs (ramelteon and M-II) in plasma and breast milk were prepared using liquid-liquid extraction (LLE) with ethyl acetate. For DORAs (suvorexant and lemborexant), LLE with ethyl acetate was applied to plasma samples. For breast milk samples, significant ion suppression was observed for LLE with ethyl acetate. Solid-phase extraction (SPE) cartridges capable of removing phospholipids improved the matrix effects. Finally, protein precipitation with methanol and an SPE cartridge, InertSep® Phospholipid Remover, were selected for breast milk sample preparation. An ACQUITY UPLC BEH C18 column was used for analyte separation. MRAs and DORAs were eluted using isocratic and gradient elution, respectively, and analyzed using electrospray ionization in the positive mode with multiple reaction monitoring. The range of calibration curve for MRAs and DORAs was 0.1-25 and 0.5-50 ng/ml, respectively. Both the plasma and breast milk samples exhibited good linearity over this range. The method was validated by evaluating its accuracy and precision, matrix effect, recovery, carry-over, stability, and dilution integrity. The validated method was successfully applied to clinical samples donated by breastfeeding women and the milk/plasma (M/P) ratio and relative infant dose (RID) of lemborexant (one case) and suvorexant (two cases) were estimated. The M/P ratio of lemborexant was <1, and the RID was 1.05 %. The M/P ratio of suvorexant was <0.1, and RID was 0.11-0.20 %. This method will be useful for future studies evaluating the safety of these drugs during breastfeeding., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Shuhei Ishikawa reports a relationship with Janssen Pharmaceutical, Otsuka Pharmaceutical, Sumitomo Pharma, EISAI, and MeijiSeika Pharma, Eli Lilly that includes: funding grants and speaking and lecture fees. Ayako Furugen is currently affiliated with the Laboratory of Healthcare Innovation Pharmacy, Faculty of Pharmacy, Keio University. This laboratory is supported by Sato Pharmaceutical Co., Ltd. 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.)

Furmonertinib, a third generation epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs), is used for non-small cell lung cancer (NSCLC). Rivaroxaban and apixaban are direct oral anticoagulants (DOACs) used for venous thromboembolism (VTE), which is a frequent comorbid with NSCLC. They are substrates of CYP3A4, P-gp and BCRP, whereas furmonertinib is an inhibitor of P-gp and BCRP. This study aimed to disclose the extent of effect of furmonertinib on the pharmacokinetics of rivaroxaban or apixaban. Rats were divided into four groups (n = 6) that received rivaroxaban (group 1), furmonertinib and rivaroxaban (group 2), apixaban (group 3), furmonertinib and apixaban (group 4). The concentrations of drugs were measured by an ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Furmonertinib increased the C max and AUC 0-t of rivaroxaban by 1.66 and 2.07-fold, whereas decreased the CL z /F by 1.70-fold and V z /F 1.27-fold. Furthermore, furmonertinib caused similar changes in apixaban pharmacokinetics. The pharmacokinetic results suggest that it is essential to alert the effect of furmonertinib on the pharmacokinetics of rivaroxaban or apixaban in clinical 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.)

The low bioavailability of insoluble flavonoids in the total flavonoids of Epimedium brevicornu Maxim. (TFE) severely hindered its clinical efficacy exertion. This research attempted to evaluate the promoting effects of pharmaceutical strategies, including nanosuspensions (NS), cyclodextrin inclusion complexes (CD), and solid dispersions (SD), on the oral absorption of active components in TFE. A rapid ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method was established to quantify ten pentenyl flavonoids of TFE in rat plasma. Good linearity was presented within the expected ranges (0.1 ∼ 10 ng/mL) in the calibration curves for ten analytes with an acceptable intra- and inter-day precision and accuracy of < 11.34 % and ± 11.91 %, respectively. By employing this selective UPLC-MS/MS method, the full-scale concentration-time curve for icariin (ICA), icariin II (ICA II), and epimedin C (EPI C) were drawn after oral administration of the crude TFE and its formulations. The results showed that the relative bioavailability (F rel ) of ICA and ICA II in the NS and CD formulations were 228-295 % when the crude TFE was as a reference, whereas the F rel of ICA, ICA II, and EPI C in SD formulation were 416 %, 234 %, and 112 %, respectively. The findings suggest that SD technology holds significant promise for enhancing the oral bioavailability of various poorly soluble ingredients in herbal extracts, such as TFE, and for augmenting their therapeutic capabilities in clinical 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.)

Numerous factors contribute to the uncertainty inherent in conducting wastewater-based epidemiology (WBE), with shifting populations exerting a significant influence. However, traditional single- and multi-parameter population models suffer from certain limitations. This study employs an evaluation model framework to construct a model (EC model) based on data characteristics. Weight coefficients derived from 16 cities across seven regions of China are aggregated into a national model. In contrast to alternative models, the EC model exhibits a robust correlation (r 2  = 0.98) with census population data, suggesting a potentially more precise depiction of population dynamics. The low variability (RSD = 9.73 %) indicates effective constraint of anomalous parameter fluctuations, yielding minimal Bias (-1.12 %) and SRMSE (14.75 %), thus ensuring reliable population estimation. The model is applied to estimate the consumption of lifestyle-related compounds and the prevalence of hypertension in China. Northern regions demonstrate higher consumption levels, alongside a significant disparity in hypertension prevalence (26.96 %) compared to the south (16.01 %). Hypertension exhibits positive correlations with lifestyle-related compounds such as alcohol and nicotine (r = 0.52, r = 0.55). Sensitivity analysis reveals that the EC model introduces an uncertainty of 24.48 % in population estimates. Through the incorporation of representative datasets and novel algorithms, this model has the potential to enhance the reliability of outcomes in WBE strategy implementation., 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.)

Context: Almonertinib is primarily metabolized by CYP3A4, so it could interact with a variety of drugs metabolized by CYP3A4, leading to the changes of systemic exposure., Objective: For the purpose of this experiment, an ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) assay with accuracy and simplicity was optimized and fully validated for the simultaneous quantitative determination of almonertinib and its metabolite HAS-719, and drug-drug interactions (DDI) between almonertinib and nicardipine in vivo and in vitro was researched., Materials and Methods: Detection of analytes was achieved by UPLC-MS/MS coupled with multiple reaction monitoring (MRM) in the positive ion mode with ion transitions of m/z 526.01 → 72.04 for almonertinib, m/z 512.18 → 455.08 for HAS-719 and m/z 447.16 → 128.11 for IS, respectively., Results: There was favourable linearity in the 0.5-200 ng/mL calibration range for almonertinib and 0.5-100 ng/mL for HAS-719. The lower limit of quantification (LLOQ) for both analytes was 0.5 ng/mL. The precision, accuracy, stability, matrix effect and extraction recovery required for methodological validation were consistent with the requirements of FDA guideline. Then, the UPLC-MS/MS assay was employed successfully on the interactions of almonertinib and nicardipine in vivo and in vitro . The half-maximal inhibitory concentration (IC 50 ) was 1.19 μM in rat liver microsomes (RLM), where nicardipine inhibited the metabolism of almonertinib with a mixed inhibitory mechanism. In pharmacokinetic experiments of rats, it was observed that nicardipine could significantly alter the pharmacokinetic profiles of almonertinib, including AUC (0-∞), AUC (0-t) and C max , but had no effect on the metabolism of HAS-719., Conclusion: According to the findings, it was indicated that nicardipine could inhibit the metabolism of almonertinib in vitro and in vivo .

Ponatinib is approved for use in patients with chronic myeloid leukemia (CML) who are resistant to or intolerant to prior tyrosine kinase inhibitor (TKI) therapy. Given that ponatinib can induce significant cardiotoxicity when taken, and that most Chinese medicines have cardioprotective effects, it is possible to administer them in combination in clinic to alleviate adverse effects. The quantitative determination of ponatinib and its metabolite N-desmethyl ponatinib was optimized and fully verified by ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS). And the drug-drug interactions (DDI) of ponatinib with lycopene and shikonin, both in vivo and in vitro, were studied. The results of bioanalytical methodology showed that ponatinib and N-desmethyl ponatinib had good linearity in plasma samples, and their selectivity, accuracy, precision, stability, matrix effect and recovery were all satisfied with the need of quantitative analysis of samples. In animal experiments, compared with the control group, lycopene and shikonin significantly changed the pharmacokinetic parameters of ponatinib, including AUC (0-t) , AUC (0-∞) and CL z/F , while having no effect on the pharmacokinetic parameters of N-desmethyl ponatinib. In vitro interaction studies indicated that lycopene showed mixed inhibition mechanism on ponatinib metabolism in both rat liver microsomes (RLM) and human liver microsomes (HLM). And, shikonin displayed mixed inhibition mechanism in RLM and competitive inhibition mechanism in HLM, respectively. In summary, the UPLC-MS/MS method can accurately and sensitively quantify ponatinib and N-desmethyl ponatinib, and provide further reference for clinical drug combination between ponatinib and lycopene or shikonin., 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 sensitive and simple method using ultra-liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was developed and validated to determine the concentration of curcumin in rat plasma and tissue samples. Emodin was selected as the internal standard (IS), and biological samples were pretreated with simple one-step acetonitrile precipitation. The calibration curves exhibited linearity within the range of 1-1000 ng/ml for both rat plasma and tissue samples. The accuracy and precision of intra-day as well as inter-day determinations ranged from 99.3% to 117.3% and from 98.2% to 105.1%, respectively. This method demonstrated excellent recovery rates ranging from 76.4% to 96.4% along with minimal matrix effect ranging from 86.5% to 99.6%. The effectiveness of this method was successfully demonstrated through its application in an in vivo pharmacokinetic and tissue distribution study after single administration via inhalation (100 mg/kg), oral gavage (100 mg/kg) and intravenous injection (2.5 mg/kg) of curcumin in rats. The results revealed that inhalation significantly improved the bioavailability of curcumin, with most of the drug being deposited in the lung. These findings highlight inhalation as an effective route for targeted delivery of drugs directly into lung tissues, thus suggesting potential future applications for treating pulmonary diseases utilizing inhaled curcumin., (© 2024 John Wiley & Sons Ltd.)

The scourge of drug addiction and abuse poses a significant challenge to society. Opioid drugs acting on μ-opioid receptor (OPRM1) make it one of the pivotal targets for drug addiction. In the past decade, sewage analysis has become a prevalent method of drug monitoring. However, traditional methods of detecting drugs in sewage are cumbersome, and rapid detection methods are relatively lacking. To address this, an innovative OPRM1-SNAP-tag/CMC method to directly identify drug components in sewage was established. Cell membrane chromatography (CMC) is an affinity chromatography technique which effectively detects receptor affinity substances. Cells constructed with high expression of specific receptor could be used to screen for compounds acting on the receptor. CMC based on OPRM1 provides a potentially convenient and effective tool for the detection of targeted drug components in sewage. In this study, the selectivity, reproducibility, column lifetime, and carryover of the CMC column had been assessed. Initially, we eluted the collected domestic sewage with methanol and acetonitrile, and the retention peaks were observed on the CMC system. Subsequently, without any preliminary sample preparation, we directly injected filtered samples of suspicious sewage into the OPRM1-SNAP-tag/CMC system, where we observed retention peaks as well. The retained components were further identified as morphine by using UPLC-MS/MS. In conclusion, the OPRM1-SNAP-tag/CMC method stands out as a reliable and robust model for the detection of drug components in sewage. It provides a valuable analytical tool for frontline drug control efforts, enhancing our capacity to monitor and mitigate the impact of drug abuse on society., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH, DE part of Springer Nature.)

Hibiscus sabdariffa L. (roselle) is a medicinal and edible plant which rich in anthocyanins with potent antioxidant properties. To enhance the stability of roselle anthocyanins, they were encapsulated in nanocapsules composed of carboxymethyl chitosan (CMC), chitosan hydrochloride (CHC), and β-lactoglobulin (β-Lg). In vitro simulated digestion assays evaluated the impact of various core-to-wall ratios and β-Lg concentrations on the bioaccessibility of seven anthocyanins. Nanocapsules with a core-to-wall ratio of 1:2 and β-Lg at 10 mg/mL exhibited the highest encapsulation efficiency (EE). Cyanidin-3-glucoside had the highest EE, while cyanidin-3-sambubioside showed the outstanding retention rate. Furthermore, simulated digestion experiments combined with molecular docking revealed that peonidin-3-glucoside and petunidin-3-glucoside likely interact with and bind to the outer β-Lg layer of the nanocapsules, increasing their release during in vitro digestion. This study demonstrates that encapsulating roselle anthocyanins in CMC, CHC, and β-Lg nanocapsules significantly enhances their bioaccessibility., 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 Ltd. All rights reserved.)

Artemisia species have been regarded as an important source of ethnic medicinal plants, such as A. annua and A. capillaris, both of which are widely used in clinical treatment. The clinical efficacy of A. japonica is similar to that of A. capillaris, but fewer pharmaceutical studies have been reported. Given that the extracts of A. japonica were observed to reduce the rectal temperature of febrile rats induced by LPS, this study was designed to demonstrate this regulatory effect of the extracts, with a particular focus on the lipidomic profiling of the febrile rat hypothalamus. A total of 72 differential metabolites were filtered out and the association between lipid profiling and potential mechanism was explored. Sphingolipid, glycerophospholipid, arachidonic acid and ether lipid metabolism pathways were significantly enriched. TNF-α, IL-6 and PGE 2 cytokines in the hypothalamus were significantly downregulated by the intervention of the extracts of A. japonica. Enzymatic reaction enrichment analysis suggested that PEMT and COX-2 might be potential targets of the efficacy, and which were testified to be downregulated by the ELISA assay under the extracts intervention., 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.)

Pathological myopia (PM) is associated with ocular morbidities that cause blindness. PM often occurs in eyes with high myopia (HM) while they are distinctly different. Identifying the differences in metabolites and metabolic pathways between patients with PM and HM may provide information about the pathogenesis of PM, which is currently unknown. This study aimed to reveal the comprehensive metabolic alterations associated with PM. Thirty patients with PM, 27 with simple HM and 27 with low myopia (LM) were enrolled in this study. Ultra-performance liquid chromatography/tandem mass spectrometry (UPLC-MS/MS) was performed, and a Venn diagram was generated to explore the overlapping differential metabolites and enriched pathways between each set of two groups. The area under the receiver operating characteristic curve (AUC) was computed to assess the discrimination capacity of each metabolite marker. A total of 134, 125 and 81 differential metabolites were identified in each comparison. Thirty-two differential metabolites were overlapped between the PM vs HM comparison and the PM vs LM comparison. Of these 32 metabolites, 16 were common to all three comparisons; among these metabolites, high levels of 4-hydroxy-l-glutamic acid and low levels of succinic semialdehyde and 2,3-dinor-8-iso prostaglandin F2α appeared to be risk factors for PM. The remaining 16 metabolites were shared only between the PM versus HM and PM versus LM comparisons, most of which are lipid molecules. Pathway analysis revealed that alanine, aspartate and glutamate metabolism was the key metabolic pathway altered in PM patients. Overall, significant differences in the metabolites and metabolic pathways were observed in patients with PM. The metabolic differences identified in this study included differential factors between PM and HM patients, addressing current gaps in PM research. These findings provide a novel perspective of the molecular mechanism of PM., Competing Interests: Declaration of competing interest The authors declare that there are no competing interests associated with the manuscript., (Copyright © 2024. Published by Elsevier Ltd.)

Polyphenols, as important active ingredients in edible fungi, have many beneficial functions. As rare edible fungi, Morchella spp., are highly popular due to their nutritional value and unique flavor. However, most Morchella have not yet been artificially cultivated due to their special biological characteristics, resulting in limited research on polyphenols in artificially cultivated Morchella. In this study, the extraction parameters of polyphenols from artificially cultivated Morchella sextelata were optimized using response surface methodology, the polyphenol components were analyzed via UPLC‒tandem mass spectrometry, and their antioxidant properties were determined in vitro. The optimal extraction process parameters were as follows: ethanol concentration, 43%; solid‒liquid ratio, 1:41 g mL -1 ; extraction temperature, 52°C; extraction time, 2 h; rotation speed, 180 r min -1 ; and extraction frequency, twice. The optimized extraction parameters resulted in a polyphenol yield of 4.82 mg g -1 , a 69.97% increase. Fourteen phenolic compounds were identified: gallic acid, protocatechuic acid, dl-4-hydroxyphenyllactic acid, methyl 2,4-dihydroxyphenylacetate, salicylic acid, 4-hydroxybenzaldehyde, 4-hydroxyacetophenone, eucommiol, luteolin, ethylparaben, hinokiflavone, amentoflavone, propyl 4-hydroxybenzoate, and 2,6-di-tert-butylphenol. The EC 50 values of 1,1-diphenyl-2-picrylhydrazyl (DPPH)· scavenging ability, reducing power and ferrous ion chelating ability of polyphenols were 2.70, 30.98, and 72.06 µg mL -1 , respectively. These findings indicated that polyphenols had a significantly stronger ability to scavenge DPPH· compared with their reducing power and ability to chelate ferrous ions. The results of this study provide a solid foundation for the subsequent study of function of M. sextelata polyphenols as well as a theoretical basis for the further development and utilization of M. sextelata, which will help promote healthy development of Morchella industry. PRACTICAL APPLICATION: The extraction, composition, and antioxidant properties of polyphenols from Morchella sextelata were identified, which provides a theoretical basis for better utilization of Morchella resources., (© 2024 Institute of Food Technologists.)

Clinical symptoms of Parkinson's disease (PD) are classified into motor and non-motor symptoms. Mental disorders, especially depression, are one of the major non-motor manifestations of PD. However, the underlying mechanisms remain poorly understood. In the present study, 21 neurotransmitters associated with mental disorders were measured in serum samples from patients and controls using the ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) assay. Additionally, five clinical scales-the MDS Unified Parkinson's Disease Rating Scale (UPDRS), the Non-Motor Symptoms Scale (NMSS), the Mini-Mental State Examination (MMSE), the Hamilton Anxiety Scale (HAMA), and the Hamilton Depression Scale (HAMD)-were used to evaluate the severity of both motor and non-motor symptoms in PD patients. Analysis of neurotransmitter metabolism revealed significant changes in the tryptophan (Trp) metabolic pathway in PD patients. Specifically, levels of Trp, kynurenine (KYN), kynurenic acid (KA), nicotinamide (NAM), and 5-methoxyltryptamine (MeOTA) were substantially decreased. Additionally, three other excitation/inhibiting amino acids-glutamic acid (Glu), 4-aminobutyric acid (GABA), and aspartic acid (Asp)-also declined. Moreover, neurotransmitter conversion ratios, such as KA/KYN, nicotinamide/niacin (NAM/NA), 5-hydroxytryptophan/tryptophan (5-HTP/Trp), and quinolinic acid/kynurenic acid (QA/KA), provided more dynamic insights into disrupted neurotransmitter metabolism. Correlation analyses between scale scores and neurotransmitter levels showed that concentrations of xanthurenic acid (XA) and the turnover rate of 3-hydroxykynurenine (3-HK) were negatively correlated with UPDRS scores, while 5-hydroxytryptamine (5-HT) and GABA levels were negatively correlated with non-motor symptoms in PD patients. In summary, this study elucidates, for the first time, the potential association and dynamics between altered neurotransmitter metabolism and the etiology of PD in terms of motor and non-motor functions. These findings offer novel biomarkers and therapeutic targets for the treatment of PD., Competing Interests: 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 Fan, Yang, Wu, Wang, Lin, Wu, Wang, Huan, Ding and Gao.)

Objective: We aimed to develop a rapid, simple, and precise ultra performance liquid chromatography - tandem mass spectrometry (UPLC-MS/MS) technique for simultaneous measurement of omadacycline (OMA) and tigecycline (TGC) in the bloodstream of individuals suffering from serious bacterial infections., Methods: All analytes were extracted using a 0.2 % formic acid-water dilution and acetonitrile plasma protein precipitation. The quantification was performed by electrospray ionization-triple quadrupole mass spectrometry with selected reaction monitoring and positive ion mode detection. Tetracycline was used as an internal standard in this experiment, with the mobile phase composed of water (with 0.1 % formic acid) and acetonitrile (using gradient elution) flowing at a rate of 0.35 ml/min, and the column temperature set at 30 °C. Each individual analysis was completed in under 3.5 min., Results: The method was validated based on FDA recommendations, including the assessment of extraction recovery (92.65-101.72 %) and matrix effects (86.22-91.12 %). The standard curve ranges for both OMA and TGC are 0.025 µg/mL to 2.5 µg/mL. The plasma samples were found to be consistent after undergoing three rounds of freezing and thawing at room temperature for 24 h, being placed in an automated sample injector for 24 h, and then frozen for 45 days. Clinical cases were used to demonstrate the application of the therapeutic drug monitoring (TDM) assay, showing how an analytical test can quickly provide information on antibiotic levels in patients and impact their treatment., Conclusion: Multiplex UPLC-MS/MS assays for the simultaneous measurement of plasma OMA and TGC concentrations are the ideal choice for clinically TDM applications., Competing Interests: 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., (© 2024 THE AUTHORS.)

Introduction: Flower characteristics are crucial ornamental and reproductive traits in Chimonanthus praecox . Over its long cultivation history, variations have been observed in the floral organs, primarily in the petals, with limited reports on stamen traits. Stamen variation, integral to the mating system, can enhance the plant's ornamental value and directly impact its reproductive success., Methods: This study is the first to report the phenomenon of red coloration in C. praecox stamens. Using UPLC-MS/MS, we analyzed the types and quantities of major metabolites in stamens of different colors., Results: Our results indicated that the red coloration was primarily due to the accumulation 42 on of high levels of anthocyanins, specifically cyanidin 3-O-rutinoside and cyanidin 3-O-glucoside. Transcriptomic sequencing identified 63 differentially expressed genes (DEGs) related to the anthocyanin biosynthetic pathway, most showing peak expression during the bud stage. The results of the metabolite analysis and transcriptomic sequencing were similar to those of previous studies on petal reddening, suggesting a close relationship between the mechanisms of stamen and petal reddening., Discussion: This study elucidated the mechanism of stamen reddening in C. praecox , expanding the species' genetic resources and offering insights into color changes across floral tissue.., Competing Interests: 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. The reviewer DL declared a shared affiliation with the authors to the handling editor at the time of review., (Copyright © 2024 Liu, Wu, Cao, Ma, Zheng, Zhu, Song and Sui.)

Background: Cnidii Fructus (CF) is a herbal medicine with pharmacological activities such as antitumor, antiviral, antiallergic, antipruritic effects, and so on., Objective: In this study, an ultra-high performance liquid chromatography/tandem mass spectrometry (UPLC- MS/MS) method was prepared and verified to measure the concentrations of seven analytes (bergapten, xanthotoxol, xanthotoxin, imperatorin, osthole, isopimpinellin, isoimperatorin) in HepG2 cells., Methods: The separation of seven analytes was performed on an ACQUITY UPLC® BEH C18 column (2.1×100 mm, 1.7 μm) with a gradient mobile phase system of 0.1% formic acid/water and acetonitrile., Results: The CV of analytes was within 7.77%, and the bias was in the range of -5.43%-3.84%. The matrix effects of analytes ranged from 92.95% to 104.58%, and the extraction recoveries ranged from 76.45% to 104.69%. The relative standard deviation of stability results was less than 8.21%, indicating that seven analytes were stable., Conclusion: The method was successfully applied to the determination of the content of seven analytes of CF extracts by UPLC-MS/MS, and the results will provide a reference for the cellular pharmacokinetics of CF., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Moringa oleifera is a vegetable rich in vitamins, minerals, and other nutrients that can be used medicinally to enhance human health. This study described how the antioxidative properties of several organs of M. oleifera were used to optimise extraction conditions through their antioxidative capacity. In addition, an analytical approach applying seven marker chemicals was developed and used to construct the chemical profile while simultaneously ascertaining the primary components and their contents in the leaf extract. Of those, the content of quercetin 3- O -malonylglucoside ( 5 ) was the greatest, at 12.50 mg/g, followed by neochlorogenic acid ( 1 ) at 5.67 mg/g. In a study using molecular docking to target antioxidation, the main constituents of the leaf extract provided some evidence. This was the first study to analyse M. oleifera grown in Suncheon and provide an effective analytical tool to control and verify the quality of this plant species by using standards.

Immunosuppressive drugs (ISDs) are given to avoid the allograft rejection after transplantation. The concentrations of ISDs should be closely monitored owing to their wide inter-individual variability in its pharmacokinetics and narrow therapeutic window. Currently, the whole blood concentration measurement is the major approach of therapeutic drug monitoring of clinical ISDs in organ transplantation. Its correlation with the efficacy of ISDs remains elusive. While the acute rejection after transplantation may occur even when whole-blood ISDs concentrations are within the target range. Since the site of action of ISDs are within the lymphocyte, direct measurement of drug exposure in target cells may more accurately reflect the clinical efficacy of ISDs. Although several methods have been developed for the peripheral blood mononuclear cells (PBMCs) extraction and drug concentration measurement, the complex pre-processing has limited the study of the relationship between intracellular ISDs concentrations and the occurrence of rejection. In this study, the extraction of ISDs in PBMCs was carried out by the liquid-liquid extraction with low temperature purification, without centrifugation. The lower limit of quantitation were 0.2 ng/mL for cyclosporine A, tacrolimus and sirolimus, 1.0 ng/mL for mycophenolic acid, and the within-run and between-run coefficient of variations were both less than 12.4 %. The calibration curves of mycophenolic acid had a linear range (ng/mL): 1.0-128.0 (r 2 = 0.9992). The calibration curves of other three ISDs had a linear range (ng/mL): 0.2-20.48 (r 2 > 0.9956). A total of 157 clinical samples were analyzed by the UPLC-MS/MS for ISDs concentration in blood or plasma ([ISD] blood or plasma ) and the concentration within PBMCs ([ISD] PBMC ). Although there was strong association between [ISD] PBMC and [ISD] blood or plasma , the large discrepancies between concentration within [ISD] blood or plasma and [ISD] PBMC were observed in a small proportion of clinical samples. The developed method with short analysis time and little amounts of blood sample can be successfully applied to therapeutic drug monitoring of ISDs in PBMCs for analysis of large numbers of clinical samples and is helpful to explore the clinical value of ISDs concentration in PBMCs., 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.)

This study developed and validated a robust UPLC-MS/MS method for quantifying cyclic glycine-proline (cGP) in mangrove-derived Penicillium and Aspergillus strains. The method demonstrated excellent linearity, precision, and recovery, with detection limits as low as 4.8 ng/mL. Penicillium pedernalense extract achieved a cGP content of 67.45 ± 1.11 ng/mL, with a corresponding fermentation yield of 29.31 ± 0.61 mg/L. This surpassed Penicillium steckii , which reached a content of 31.71 ± 0.31 ng/mL, with a yield of 8.51 ± 0.15 mg/L. This quantitative approach for metabolite analysis provides a viable method for screening these fungal strains, highlighting their potential for sustainable production of cyclic glycine-proline (cGP).

We established a method based on ultra performance liquid chromatography tandem mass spectrometry (UPLC‒MS/MS) to quantitatively measure tepotinib, which was validated as acceptable and used in the evaluation of food-drug interactions between tepotinib and naringenin in rats. We used pemigatinib as the internal standard (IS), and acetonitrile and 0.1% formic acid aqueous solution constituted the mobile phase. To extract the target analyte, acetonitrile was used for protein precipitation (PPT). For UPLC‒MS/MS, we performed liquid chromatography using a C18 column, and mass spectrometry was performed in positive multiple reaction monitoring (MRM) mode. Excellent linearity was shown in the range of 0.1-500 ng/mL, and the coefficient of correlation was > 0.99. Notably, the lower limit of quantification (LLOQ) for tepotinib was determined to be 0.1 ng/mL. The intra- and inter-day accuracy of tepotinib ranged from - 1.7 to 7.3%, while the precision was ≤ 8.4%, at three concentrations except LLOQ. The recovery of each substance was ≥ 81.2%, and the matrix effects were within 90.5-98.6%. The stabilities of all analytes under different conditions met all requirements for quantitation in plasma samples. The relevant parameters, such as LLOQ, were evaluated in accordance with the principles of the Food and Drug Administration (FDA) biological verification method. Food-drug interaction study had shown that the plasma concentration of tepotinib could be significantly increased, accompanied by a decrease in clearance rate when administered with 50 mg/kg naringenin. The results showed that naringenin could increase the plasma concentration and decrease the clearance rate of tepotinib when naringenin and tepotinib were administered at the same time., (© 2024. The Author(s).)

Furmonertinib (AST2818) is a selective epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) being developed for the treatment of patients with EGFR mutation-positive non-small cell lung cancer. Quantification of furmonertinib in plasma and cerebrospinal fluid (CSF) can be used to assess penetration of furmonertinib into the central nervous system (CNS). This paper described ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) methods for quantification of furmonertinib in human plasma and CSF. Sample separation was achieved on a Kinetex C 18 column (100 mm × 2.1 mm, 2.6 μm) after simple protein precipitation with acetonitrile. The mobile phase was composed of acetonitrile and 5 mM ammonium acetate with 0.2 % formic acid in water. Quantitative ion pairs were m/z 569.3 → 72.2 for furmonertinib and m/z 526.5 → 72.2 for aumolertinib, which was used as the internal standard (IS). The calibration curves showed good linearity (r 2  > 0.99) over concentration range of 0.5-200 ng/mL(plasma sample) and 0.05-30 ng/mL(CSF sample). The precision (RSD) was ≤7.86 %, and the accuracy fell within the range of 96.2 %-109.3 %, all meeting acceptance criteria. The matrix effect was from 94.3 % to 102.1 %. The recovery of analytes fell within the range of 93.3 %-98.9 %. The established analytical methods showed great sensitivity, simplicity, accuracy and reliability for the analysis of furmonertinib in human plasma and CSF. This assay would be helpful to predict the effectiveness and toxicities of furmonertinib in the pursuit of precision medicine for lung cancer patients., 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.)

Biancaea decapetala (Roth) O.Deg. (Fabaceae), traditionally utilized by the Hmong for treating rheumatoid arthritis (RA), has its pharmacokinetic behavior under disease conditions largely unexplored. In view of this, a UPLC-MS/MS method was established for the determination of protosappanin B (PTB), protosappanin B-3-O-β-D-glucoside (PTD), and 3-deoxysappanchalcone (3-DSC), key bioactive components of the herb, in rat plasma and RAW264.7 cells to explore the effect of disease state on the pharmacokinetic profiles changes of these three components in vitro and in vivo. These components were detected using multiple reaction monitoring (MRM) process in positive and negative mode. Each calibration curve had a high R 2 value of > 0.99. The intra- and inter-day precisions of PTD, PTB, 3-DSC were all < 15 %, and accuracy ranged from 85 % to 115 %. The RSD values pertaining to stability, recovery, matrix effect, and stability remained below 15.0 %. It was successfully applied for the investigation of the pharmacokinetics of these three components in rat plasma and RAW264.7 cells after administration of Biancaea decapetala extracts (BDE). In rat pharmacokinetic experiments, significant differences were observed in the AUC (0-t) , MRT (0-t) , and Cl z /F values of PTD, PTB, 3-DSC between adjuvant-induced arthritis (AA) and normal rats. In cellular pharmacokinetic experiments, comparison with the normal group revealed increased AUC (0-t) and MRT (0-t) for these three components in the LPS-induced inflammatory cell model, along with decreased Cl z /F, which was consistent with in vivo experimental outcomes. These findings suggest an increased absorption rate and a decreased elimination rate of the three components of BDE in AA rats and inflammatory cells, indicating a potential alteration in the rate and extent of drug metabolism. This study provided a theoretical reference for further clarification of its pharmacodynamic basis., 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.)

Huperzine A is a reversible and selective cholinesterase inhibitor and has been approved for the treatment of Alzheimer's diseases. In this study, we developed a highly sensitive and specific ulta-high-performance liquid chromatography-tandem mass spectrometry method for the determination of Huperzine A in rat plasma. An aliquot of 50 μL of rat plasma sample was pretreated with 200 μL of acetonitrile-methanol (v/v; 1:1) containing 0.2% formic acid followed by solid phase extraction. The resulting sample was separated on a Waters ACQUITY BEH C 18 column using acetonitrile and water containing 0.2% formic acid as mobile phase, at a flow rate of 0.3 mL/min. Multiple-reaction monitoring (MRM) mode was used for quantitative analysis of Huperzine A in positive electrospray ionization. In the concentration range of 0.01-10 ng/mL, Huperzine A showed excellent linearity with correlation coefficient > 0.998. The intra- and inter-day RSD% were less than 9.7%, while the RE% ranged from -6.7% to 10.0%. The mean recovery was >84.5%. The validated method was demonstrated to be selective, sensitive, and reliable, which has been successfully applied to pharmacokinetic study of Huperzine A in rat plasma. Huperzine A displayed a long half-life in rat plasma and high oral bioavailability., (© 2024 John Wiley & Sons Ltd.)

Global warming due to climate change, as well as freshwater eutrophication caused by anthropogenic activities are responsible, among other factors, for an increasing occurrence of harmful algal blooms (HABs) in aquatic systems. These can lead to the generation of cyanotoxins, secondary metabolites coming from cyanobacteria, producing adverse effects in living organisms including death. This research aims to study the effects that two neurotoxins, anatoxin-a (ATX-a) and saxitoxin (STX), have on living organisms. Once the stability of both compounds in water was determined for a 24 h period using ultra-high-performance liquid chromatography coupled to a triple quadrupole mass spectrometer (UPLC-MS/MS), zebrafish larvae were exposed to different levels of toxins (1 ng L -1 , 10 ng L -1 , 100 ng L -1 and 1 μg L -1 ) during 24 h. Behavioral studies including vibrational startle response (VSR), habituation to vibrational stimuli, basal locomotor activity (BLM) and visual motor response (VMR) were performed using Danio Vision system, and neurotransmitters (NTs) from 15-head pools of control and exposed zebrafish larvae were extracted and analyzed by UPLC-MS/MS. Both compounds induced hypolocomotion in the individuals, while 10 and 100 ng L -1 of ATX-a significantly increased methionine (120 % and 126 %, respectively) and glutamate levels (118 % and 129 %, respectively). Saxitoxin enhanced 3-metoxytyramine (3-MT) levels at 1 ng L -1 by 185 %. The findings of this study show that both studied cyanotoxins influence the behavior of zebrafish larvae as well as their metabolism., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Cristian Gomez Canela reports financial support was provided by Spain Ministry of Science and Innovation. 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.)

Azodicarbonamide (ADA) is approved as a food additive in flour products due to its oxidising and bleaching properties. However, it is prohibited in Australia and Europe on account of its toxicity and the risk of causing asthma in humans. A method was developed to determine ADA in actual flour samples. This work presents an optimised methodology based on derivatisation and clean-up procedures followed by ultra-performance liquid chromatography coupled with electrospray ionisation tandem mass spectrometry (UPLC-ESI-MS/MS). The analytical method was successfully validated. An excellent result was obtained for the linearity of matrix-matched calibration curves ( R 2  > 0.99) in the concentration range of 0.10-80 mg/kg. The recovery rate varied from 81.7% to 102.3%. The relative standard deviations (RSDs) of repeatability ( n  = 6) were 1.3-4.1%, and inter-day RSDs ( n  = 6) were 2.2-4.8%. The limit of detection and the limit of quantification were 0.014 and 0.042 mg/kg, which were significantly lower than the requirement of 45 mg/kg stipulated in the Chinese National Food Safety Standard (GB 2760-2014). The detection rate of ADA in 26 flour samples was 23.1%, with the concentration ranging from 0.023 to 23.2 mg/kg.

Yigong San (YGS) is a traditional Chinese medicine formula used for pediatric anorexia, chronic atrophic gastritis, and irritable bowel syndrome. In this study, the excretion of eight main compounds, including liquiritin; isoliquiritin; hesperidin; ginsenosides Rb 1 , Re, and Rg 1 ; and atractylenolides I and II, in rat urine, feces, and bile, was investigated by ultra-high performance liquid chromatography-tandem mass spectrometry. The results showed that the cumulative excretion rates of the compounds in rat urine, feces, and bile were 0.018-1.15%, 0.024-19.89%, and 0.0025-0.72%, respectively. Among the eight compounds detected, liquiritin was the richest in urine, and ginsenosides Re and Rg 1 and atractylenolide I were mainly found in feces and bile. In summary, the main components of YGS are excreted via multiple approaches. Liquiritin is mainly through urine, whereas isoliquiritin; hesperidin; ginsenosides Rb 1 , Re, and Rg 1 ; and atractylenolides I and II are mainly through feces. The excretion of these compounds in bile is usually positively correlated with that in feces. This study lays a foundation for further pharmacological research and application of YGS., (© 2024 John Wiley & Sons Ltd.)

UPLC-MS/MS analytical conditions for the analysis of aflatoxins in spices were optimized and validated in this study. Liquid-liquid partition-based protocols for the cleaning up of extracts using common organic solvents such as acetonitrile, hexane, and ethyl acetate were developed and validated. The developed liquid-liquid partition methods were compared with immuno-affinity column and QuEChERS clean-up methods for the UPLC-MS/MS analysis of aflatoxins in 8 spices. The reduction of lipophilic components using the partition with hexane is particularly useful in spices like red pepper that have higher levels of fatty acids, carotenoids, sterols, triterpenoids, etc. The subsequent partitioning with ethyl acetate considerably reduced the matrix interference from the polar components and increased the sensitivity. The cleaning up of spice extracts using liquid-liquid partition techniques resulted in limits of quantification (LOQ) of 2-5 µgL -1 in UPLC-MS/MS analysis. Trueness, repeatability, and reproducibility of the methods were in acceptable ranges. The accuracy of the developed methods was further verified by analyzing aflatoxins in naturally incurred samples of spices and comparing the results with those obtained from the immuno-affinity column cleanup-HPLC-FD method., (© 2024. The Author(s) under exclusive licence to Society for Mycotoxin (Research Gesellschaft für Mykotoxinforschung e.V.) and Springer-Verlag GmbH Germany, part of Springer Nature.)

Alternaria toxins (ATs) are produced from Alternaria species that result in crop losses and harmful impacts on human health. A stable isotope dilution LC-MS/MS method was established to quantify four ATs in 15 food commodities: alternariol (AOH), alternariol monomethyl ether (AME), tentoxin (TEN), and tenuazonic acid (TeA). Based on systematically optimization of detection conditions and pre-processing steps, the limits of detection and limits of quantification of the four ATs ranged from 0.1 to 10 μg/kg and 0.2 to 30 μg/kg, respectively. The results showed that the recoveries of the four ATs were 72.0%-119.1%. The intra-precision and inter-precision ranged from 0.7% to 11.1% and 1.1% to 13.1%, respectively. The method was successfully applied to the determination of four ATs in 35 food samples, suggesting that this method could provide meaningful occurrence data to support the assessment of emerging ATs in food commodities., 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 Ltd. All rights reserved.)

Metformin is the gold standard substrate for evaluating potential inhibitors of the organic cation transporters (OCTs). Here, we established a UPLC-MS/MS assay to quantify metformin in cell pellets with a range of 0.05-50 ng/mL using 6-deuterated metformin as an internal standard. We used an ion-pairing chromatographic approach with heptafluorobutyric acid, making use of a reverse-phase column, and overcame the associated ion-suppression via previously established post-column injection of aqueous ammonia. The assay was validated according to the Food and Drug Administration (FDA) and the European Medicines Agency (EMA) recommendations for bioanalytical methods. The established extraction procedure was simple, very fast and ensured almost 100% recovery of the analyte. The exceptionally sharp peak form and retention of the ion-pairing chromatography are superior to other methods and allow us to measure as sensitively as 0.05 ng/mL. We used the herein established and validated method to develop a cellular OCT inhibition assay by using metformin as a substrate and human embryonic kidney cells (HEK) overexpressing the OCTs 1-3. The method presented may be useful for identifying new OCT inhibitors, but also for drug-drug interactions and other pharmacokinetic studies, where accurate quantification of low metformin amounts in relevant tissues is mandatory.

Flavonoids possess antioxidant properties and are crucial in enhancing plant resistance to abiotic stress. Exogenous calcium has been found to regulate the biosynthesis and accumulation of secondary metabolites, including flavonoids. However, the mechanism by which exogenous calcium influences flavonoid regulation in peanut roots under salt stress remains unclear. In this study, four treatment conditions were established: no salt stress, salt stress, exogenous calcium, and a combination of salt stress and exogenous calcium. The peanut root flavonoid profile was comprehensively analyzed using both a broadly targeted metabolomic approach and an absolute quantitative flavonoid metabolome. A total of 168 flavonoids were identified in the broad-target metabolome, while 68 were quantified in the absolute quantification analysis. The findings revealed that salt stress generally increased flavonoid content in peanut roots, while co-treatment with exogenous calcium significantly reduced this accumulation. Additionally, the activities of key enzymes and the expression of genes involved in the flavonoid biosynthesis pathway were upregulated under salt stress, but downregulated following the combined treatment. This study offers valuable insights into the physiological and ecological roles of flavonoids in response to environmental stressors in economically important crops., Competing Interests: 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 Gao, Dong, Wang, Zhang, Hao, Niu, Zhang and Lin.)

Both sedative and antipathogenic drugs are often found to be illegally used in aquaculture, but there is a lack of simultaneous monitoring methods. A method for simultaneously monitoring multiple prohibited drugs in various aquatic product samples was developed in this work, including fish, shrimp, crab, and shellfish. Sulfonic acid-functionalized magnetic graphitic carbon nitride (S-MGCN) was synthesized and validated to efficiently co-extract all targets (adsorption efficiency over 90.07%) through various adsorption mechanisms such as electrostatic interaction, hydrogen bonding, and π-π interaction while demonstrating good sample matrix purification ability (matrix effect below 13.60%). A new magnetic solid-phase extraction method based on S-MGCN was subsequently established. Coupled with UPLC-MS/MS, the detection limits were 0.030.075 μg /kg, and the recoveries ranged from 88.76% to 111.74% with the RSDs lower than 14.60%, indicating that the developed method has good sensitivity, accuracy, and precision. Further validation of its practicality was achieved through actual sample analysis., 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 Ltd. All rights reserved.)

Pterocephin A is a natural triterpenoid saponin isolated from Pterocephalus hookeri , a traditional Tibetan medicine with slight toxicity, which can induce liver injury in rats. This study aimed to establish a sensitive and reliable UPLC-MS/MS method for exploring the toxicokinetics and tissue distribution of pterocephin A following single intravenous and intragastric administration. Pterocephin A and prosapogenin 1C (internal standard, IS) were extracted using a simple protein precipitation technique with methanol as the precipitant for plasma samples and methanol/acetonitrile = 1:1 ( v / v ) for tissue samples. UPLC separation was achieved by gradient elution with 0.3 mL/min and a mobile phase consisting of 5 mM ammonium formate (A) and acetonitrile (B) (0-2 min 30% B; 2-4 min: 30-80% B; 4-5 min: 80-98% B; 5-6.5 min: 98% B; 6.5-7 min: 98-30% B; and 7-8 min: 30% B, v / v ) with a column temperature of 35 °C. MS spectrometry adopted negative ion scanning mode, primary MS spectrometry adopted full scan monitoring mode, and secondary MS spectrometry adopted targeted MS2 scan monitoring mode. The assay exhibited a linear dynamic range of 0.02-15 μg/mL for pterocephin A in biological samples, with the low limit of quantification set at 0.02 μg/mL. Non-compartmental toxicokinetic parameters indicated that pterocephin A was well absorbed into the systemic circulation and had a long residual time after intravenous (10 mg/kg) and intragastric (60 mg/kg) administration, as it could still be detected after 72 h. Tissue distribution analysis revealed detectable levels of pterocephin A in various tissues, and a high concentration was maintained in the liver after intravenous (10 mg/kg) administration, with the highest concentration being 610.95 ± 25.73 ng/mL and a specific distribution pattern of liver > lung > kidney > intestine > spleen > testes > heart > stomach. The toxicokinetic process and tissue distribution characteristics of pterocephin A were expounded in this study, which can provide relevant data support for further research and clinical application of pterocephin A with its slight toxicity.

Introduction: A rapid, accurate, and specific ultrafiltration with ultra-performance liquid chromatographic-tandem mass spectrometry method was validated for the simultaneous determination of the protein binding rate of atorvastatin in uremic patients. Methods: The plasma samples were centrifuged at 6,000 r/min for 15 min at 37°C and the ultrafiltrate was collected. An ACQUITY UPLC® BEH C18 Column with gradient elution of water (0.1% formic acid) and acetonitrile was used for separation at a flow rate of 0.4 ml/min., Results: The calibration curves of two analytes in the serum showed excellent linearity over the concentration ranges of 0.05-20.00 ng/ml for atorvastatin, and 0.05-20.00 ng/ml for orthohydroxy atorvastatin, respectively. This method was validated according to standard US food and drug administration and European medicines agency guidelines in terms of selectivity, linearity, detection limits, matrix effects, accuracy, precision, recovery, and stability. This assay can be easily implemented in clinical practice to determine the free and combined concentrations of atorvastatin in the plasma of uremic patients. The final result showed that the average plasma protein binding rate in uremic patients was 86.58 ± 2.04%, relative standard deviation (RSD) (%) = 1.98, while the plasma protein binding rate in patients with normal renal function was 97.62 ± 1.96%, RSD (%) = 2.04. There was a significant difference in the protein binding rate in different types of plasma ( P < 0.05), and the protein binding rate decreased with increasing creatinine until it stabilized at nearly 80%. The mean metabolite/prototype ratio of atorvastatin in patients with normal renal function and in patients with uremia was 1.085 and 0.974, respectively., Discussion: The metabolic process of atorvastatin may be inhibited in uremic hemodialysis patients, but the total concentration of atorvastatin did not change significantly; due to the decrease of protein binding rate increase the drug distribution of atorvastatin in the liver or muscle tissue, which may increase the risk of certain adverse reactions. We recommend that clinicians use free drug concentration monitoring to adjust the dose of atorvastatin to ensure patient safety for uremic hemodialysis patients., Competing Interests: 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., (© 2024 Cao, Huang, Tang, Shi, Zheng and Zhao.)

Objective: An UPLC-MS/MS method was developed and validated for simultaneous determination of atracurium (ATC), dexmedetomidine (DEX), midazolam (MDZ) and 1-hydroxymidazolam (1-OH-MDZ) and the pharmacokinetics of ATC, DEX, MDZ and 1-OH-MDZ in patients undergoing aortic dissection surgery were investigated., Methods: The analytes were extracted by acetonitrile precipitation and separated on an Acquity UPLC BEH C18 column (2.1 mm × 50 mm, 1.7 μm) with a mobile phase of acetonitrile-0.1% formic acid and a gradient mode. In the positive ion mode, the following mass transition pairs were monitored by multiple reaction monitoring (MRM) for the four analytes and IS: m/z 385.1→206.2 for ATC, m/z 201.2→95.1 for DEX, m/z 326.1→291.1 for MDZ, m/z 341.9→324.0 for 1-OH-MDZ, and 284.9→153.9 for diazepam (IS). Seven male patients undergoing aortic dissection surgery received general anesthesia and intravenous administration of ATC, DEX, and MDZ during the surgery. Venous blood was collected at different time points at the end of surgery and after surgery. The concentrations of ATC, DEX, MDZ, and 1-OH-MDZ were detected, and the pharmacokinetic parameters were calculated., Results: The method showed good linearity for each analyte. The inter-batch precision ranged from 1.37% to 9.87% and the intra-batch precision ranged from 2.41% to 10.72%; the accuracy ranged from 94.33% to 104.51%. Finally, the matrix effect, extraction recovery and stability data met the FDA recommended acceptance criteria for validation of bioanalytical methods. The t 1/2 of ATC, DEX, MDZ and 1-OH-MDZ was (6.74 ± 2.27) h, (9.55 ± 4.93) h, (10.17 ± 5.35) h, and (6.90 ± 2.38) h, the C max , of ATC, DEX, MDZ and 1-OH-MDZ was (1054.20 ± 202.37) ng/mL, (1.93 ± 1.07) ng/mL, (1256.57 ± 389.09) ng/mL, and (1034.39 ± 292.92) ng/mL in patients undergoing aortic dissection surgery, respectively., Conclusion: The developed UPLC-MS/MS method for simultaneous determination of ATC, DEX, MDZ and 1-OH-MDZ in patient plasma was accurate, reproducible, specific. After continuous administration of ATC, DEX, and MDZ to patients undergoing surgery for acute aortic dissection, the pharmacokinetics of ATC, DEX, MDZ and 1-OH-MDZ in patients undergoing aortic dissection surgery were studied., Competing Interests: 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. The reviewer YS declared a shared affiliation, though no other collaboration, with several of the authors (HS, XX, YL, SS) to the handling Editor., (Copyright © 2024 Si, Xu, Liang, Shi, Xie and Hu.)

Based on the effectiveness, measurability, and traceability of the quality marker (Q-marker) theory of traditional Chinese medicine, the Q-marker of Lycii Cortex (LC) was preliminarily predicted and analyzed. A UPLC-Q-TOF-MS qualitative analysis method for LC samples was established. A total of 44 LC chemical components, 16 plasma prototype components, 25 urine prototype components, and 27 fecal prototype components were identified. At the same time, the "component-target-disease" network diagram was constructed by network pharmacology to predict the potential active components of LC. A UPLC-MS/MS quantitative analysis method was established to determine the contents of 11 components such as kukoamine A in 35 batches of LC from seven producing areas. Principal component analysis, orthogonal partial least squares discriminant analysis, and other mathematical analysis methods were used to screen the differential components. Based on the comprehensive consideration of the Q-marker traceability, transitivity, specificity, effectiveness, and measurability, kukoamine A and kukoamine B were preliminarily predicted as LC potential Q-markers, and the high-quality producing area was determined to be Chengcheng County, Weinan City, Shaanxi Province. The prediction analysis of the LC Q-marker provides a reference for the comprehensive control of the quality of LC medicinal materials and also lays a foundation for the research and exploration of the substance basis and mechanism of action of LC., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 Xinrui Wang et al.)

Objective: To develop a method for determining the concentration of axitinib in beagle dog plasma and utilize this method to investigate the pharmacokinetics of orally administered axitinib in beagle dogs., Methods: Plasma samples were processed using acetonitrile precipitation and analyzed by UPLC-MS/MS with sunitinib as an internal standard (IS). Chromatographic separation was achieved on a Waters Acquisition UPLC BEH C18 column (50 mm × 2.1 mm, 1.7 μm) with a gradient elution of acetonitrile and 0.1 % formic acid. Mass spectrometry uses an electrospray ion source for positive ion detection in a multiple reaction monitoring mode. The monitored ion transitions for axitinib and sunitinib were m / z 387 → 355.96 and m / z 399.3 → 282.96, respectively. Six beagle dogs were administered 0.33 mg/kg of axitinib orally, and venous blood samples were collected at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 h post-dose for pharmacokinetic analysis., Results: The assay demonstrated a linear range of 0.5-100 ng/mL (r 2  = 0.9992), and the lower limit of quantification was up to 0.5 ng/mL. Precision, as assessed by relative standard deviation (RSD), was within 8.64 % for both intraday and interday variability. The relative error (RE) for precision from -2.77 %-1.20 %. The recovery rate of the analytes exceeded 85.28 % and the matrix effect was approximately 100 %. Plasma samples maintained stability under various conditions, including room temperature storage for 12 h, processed on an automatic sampler at 4 °C for 6 h, three freeze-thaw cycles, and long-term storage at -80 °C for 60 days. Pharmacokinetic parameters were determined using DAS 2.0 software, revealing a half-life (T 1/2 ) of 6.05 h and an area under the curve (AUC (0 → ∞) ) of 97.13 ng h/mL for axitinib., Conclusions: The UPLC-MS/MS method developed in this study offers high specificity, rapid analysis, high recovery, excellent linearity, and minimal plasma volume requirements, making it well-suited for pharmacokinetic and drug interaction studies in beagles dogs., Competing Interests: 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., (© 2024 The Authors.)

Pectolinarigenin (PEC), a natural flavonoid isolated from Cirsium japonicum, exhibits promising therapeutic potential for multiple cancers. In present study, a simple and sensitive UPLC-MS/MS method was established for the quantification of PEC in rat plasma and tissues. The assay procedure involved a one-step protein precipitation with tadalafil as the internal standard, and separation on a Welch Xtimate UHPLC C 18 column by gradient elution of acetonitrile/aqueous formic acid (0.1 %, v/v) at a flow rate of 0.2 m L·min -1 . The detection was conducted using multiple-reaction monitoring via an electrospray ionization source in positive ionization mode. The established method was proved to be highly sensitive with a good linearity (R 2  > 0.99) in respective concentration range (0.1-100 ng·mL -1 in plasma and 1-10,000 ng·mL -1 in tissues) and acceptable extraction recovery (≥71.17 %), matrix effect and stability, which was applied to study the pharmacokinetics and tissue distribution of PEC after intravenous (100 μg·kg -1 ) and oral administration (10, 20 and 40 mg·kg -1 ). PEC was promptly absorbed (T max  ≤ 0.222 h) and maintained at a low level with slow elimination (t 1/2 z  ≥ 14.47 h) in rats after oral administration, resulting in extremely low bioavailability (0.56-0.68 %). However, PEC is widely distributed in rat tissues with high exposure in GI tract, liver and kidney. The bioavailability and tissue affinity were firstly revealed, which would guide directions for further development of PEC as an anti-tumor drug candidate., 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.)

Slow transit constipation (STC) is a common intestinal disorder. Some studies reported that Shouhui Tongbian Capsule (SHTB) can effectively mitigate STC symptoms. A detailed understanding of the changes in the endogenous metabolite profile of rats is crucial for a more accurate comprehension of the molecular pathological characteristics of SHTB in treating STC. In the present study, a method integrating metabolomics based on Ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) and Desorption electrospray ionization (DESI)-mass spectrometry imaging (MSI) was proposed to investigate serum, feces and colon tissue metabolic alterations of STC rats induced by diphenoxylate and the effect of SHTB treatment on metabolism. Then, Enzyme-linked immunosorbent assay (ELISA) and Western blot (WB) analysis for verifying the potential mechanism of SHTB in treating STC. As a result, we first indicated that SHTB significantly improved intestinal peristalsis and low fecal water content in STC rats. Furthermore, after treatment with SHTB, the thickness of muscle layers was increased, demonstrated SHTB's effectiveness in reducing intestinal injury in STC rats. Besides, bile acid (BA) metabolomics based on UPLC-MS/MS revealed significant increase in serum levels of Cholic acid (CA), Deoxycholic acid (DCA), Chenodeoxycholic acid (CDCA), Ursodeoxycholic acid (UDCA), and Glycolithocholic acid (GLCA), whereas the contents of CA and DCA in feces were significantly decreased in STC rats. Nonetheless, they returned to the control levels after the SHTB administration. ELISA results showed that SHTB significantly hindered the excessive reabsorption of BAs by inhibiting apical sodium-dependent bile acid transporter (ASBT), organic solute transporter alpha (OSTα) and organic solute transporter beta (OSTβ) in the ileum tissue of STC rats. Furthermore, the DESI-MSI analysis revealed that SHTB remarkably enhanced DCA in the colon tissue of STC rats. The WB results indicated that SHTB reinstated Takeda G-protein-coupled receptor 5 (TGR5) expression, a receptor for BAs and a key regulator of colonic motility. Consequently, DCA exerted its effects on TGR5, leading to the promotion of colonic motility. This study provided more comprehensive and detailed information about the BA metabolomics in the serum, feces and colon of STC rats. These findings highlighted the promising potential of metabolomics based on UPLC-MS/MS and DESI-MSI method for application in the study of STC diseases., 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.)

Taletrectinib is a potent selective ROS and pan-NTRK tyrosine kinase inhibitor (TKI) and has been developed to treat non-small cell lung cancer (NSCLC). To facilitate pharmacokinetic and toxicokinetic studies of taletrectinib, we developed a procedure for ultra-high-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) to detect the plasma level of taletrectinib in dogs. This assay procedure was validated in compliance with FDA guidance. The dog plasma samples were spiked with internal standard (IS), followed by protein precipitation, and analyzed using a Waters ACQUITY BEH C 18 column coupled to a Thermo triple quadrupole mass spectrometer. Separation was executed using the acetonitrile-0.1 % formic acid solution with gradient elution, at a flow rate of 0.4 mL/min. Taletrectinib and IS were monitored by multiple reaction monitoring (MRM) with m/z 406.2 > 349.2 and m/z 441.2 > 138.1, respectively. The procedure demonstrated excellent linearity with a correlation coefficient greater than 0.999 within the concentration range of 0.2-200 ng/mL. The inter- and intra-day accuracy ranged from -5.25 % to 5.26 %, and the precision was below 6.39 %. Acetonitrile-mediated protein precipitation showed high extraction efficiency and a recovery above 85 %. The procedure was then applied to quantify taletrectinib in beagle dog plasma after oral and intravenous doses and achieved success. The obtained pharmacokinetic parameters indicated high bioavailability of taletrectinib (>85 %) and extensive tissue distribution (>40 L/kg)., 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 cancer development and progression, the Hippo signaling pathway functions. The transcriptional enhanced associate domain (TEAD) stands out as a pivotal transcription factor within this pathway, and the suppression of TEAD represents a promising approach for cancer treatment. The primary aim of the study was to establish an analytical method for the concurrent quantification of a novel TEAD target inhibitor, BPI-460372, and its principal metabolites, BPI-460444 and BPI-460456, in human plasma. The chromatographic separation utilized a XSelect™ HSS C 18 column (2.1 × 100 mm, 2.5 µm), while quantification was conducted on a SCIEX API 4000 mass spectrometer. 22 plasma samples were tested via the developed method. The calibration curve for BPI-460372 exhibited linearity from 2 to 2000 ng/mL, while its metabolites BPI-460444 and BPI-460456 had linearity between 1 and 1000 ng/mL (r > 0.99). The precision (RSD) was ≤ 17.1 %, and the accuracy (RE) fell within the range of -17.7 % to 15.0 %, all meeting acceptance criteria. The matrix effect was from 101.0 % to 105.8 %. The extraction recovery of analytes fell within the range of 96.8 % to 104.1 % with an RSD of less than 7.4 %. The developed method was effectively utilized in an advanced solid tumor patient, and the concentration trends of the three analytes in plasma were found to be largely consistent. The established analytical method showed great sensitivity, simplicity, accuracy, and reliability for the rapid and simultaneous analysis of the TEAD target inhibitor BPI-460372, alongside its major metabolites BPI-460444 and BPI-460456 in human plasma. This analytical method provided essential support for future clinical investigations and pharmacokinetic analysis., 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.)

Fuzuloparib is a novel orally bioactive poly-ADP-ribose polymerase inhibitor (PARPi), which was approved by the Chinese Regulatory Agency (CRA) in 2020 for the treatment of platinum-sensitive recurrent ovarian, fallopian tube, and primary peritoneal cancers. This study firstly presents a rapid and accurate ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method for analyzing the levels of fuzuloparib and its major metabolite (SHR165202), and to investigate drug-drug interaction between fuzuloparib and curcumin in vitro and in vivo studies. After protein precipitation with acetonitrile, mobile phase consisted of acetonitrile and 0.1 % formic acid with a gradient elution was used to successfully separate fuzuloparib, SHR165202 and talazoparib (internal standard, IS). The results indicated that fuzuloparib and SHR165202 had good linearity over the calibration range of 2-50 ng/mL and 1-20 ng/mL, respectively. The precision, accuracy, stability, matrix effect, and extraction recovery required for methodological validation all complied with the requirements of the Bioanalytical Method Validation Guidelines. In vitro microsome incubation experiments, curcumin exhibited inhibitory effect on fuzuloparib in both rat liver microsomes (RLM) and human liver microsomes (HLM) with half-maximal inhibitory concentration (IC 50 ) value of 10.54 μM and 47.64 μM, respectively, and the corresponding mechanism was non-competitive. Furthermore, the inhibitory mechanism of curcumin on fuzuloparib was validated through molecular docking. In pharmacokinetic experiments in rats, curcumin significantly altered the plasma exposure of fuzuloparib, resulting in significant increases in AUC (0-t) and C max of fuzuloparib and a significant decrease in CL z/F . Moreover, the metabolite SHR165202 showed significant increases in AUC (0-t) , AUC (0-∞) , T max and C max and a significant decrease in CL z/F . This further supports the notion that curcumin could inhibit the metabolism of fuzuloparib. Therefore, when co-administering fuzuloparib and curcumin in clinic, it is recommended to monitor plasma levels of fuzuloparib and pay close attention to adverse effects. If necessary, the dose of fuzuloparib needs to be reduced., 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 aim of the present study was to establish a simple and reliable ultra-high-performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) method and apply it for the determination of pharmacokinetics of moxidectin-loaded microspheres (MOX-MS) in rats. Plasma samples were processed using a simplified liquid-liquid extraction method and were separated using an Agilent Zorbax Eclipse Plus C18 column (50 mm × 2.1 mm, 1.8 μm) with a mobile phase consisting of a 10 mM ammonium formate solution with 0.1% formic acid (A) and acetonitrile (B) at a flow rate of 0.4 mL/min for 5 min. Avermectin B1a was used as an internal standard (IS). The sample was injected at a volume of 10 μL with a column temperature of 35 °C and detected in a positive ion mode. A good linear response across the concentration range of 1.00-200 ng/mL (r 2 > 0.99) and a lower limit of quantification (LLOQ) of 1.00 ng/mL were achieved. The extraction recovery of moxidectin exceeded 94.1%, the matrix effect was between 91.2% and 96.2%, the accuracy ranged from 100.1 to 103.6%, and the relative standard deviation (RSD) did not exceed 15% for the intra- and inter-day accuracy and precision. The pharmacokinetic results showed that MOX-MS significantly decreased C max , prolonged T 1/2 , and improved bioavailability. The developed method significantly reduced the assay volume, shortened detection time, simplified sample processing methods and saved assay costs, which may contribute to the development of the new antiparasitic drug.

Ectoine (ECT) has recently gained considerable interest in the healthcare sector due to its promising therapeutic benefits in a variety of human disorders. This research aimed to quantify the ECT plasma level in rats by creating and optimizing a sensitive and validated UPLC-MS/MS method. Prior to analysis, ECT extraction from the plasma samples was conducted via a protein precipitation procedure, using hydroxyectoine as an internal standard (IS). A 1.7 μm UPLC C8 column (100 mm × 2.1 mm) was selected for the chromatographic separation, using a gradient mobile phase consisting of acetonitrile and 0.05% formic acid. The electrospray ionization mass spectrometry (ESI-MS) was used to detect ECT in the positive ion mode. To determine the specific precursor and the product ions of ECT, multiple reaction monitoring (MRM) methods were carried out. The selected ion pair of ECT was 143.1 > 97 and 159.1 > 113.13 for the IS. The ECT's linearity range in rat plasma was found to be 1-1000 ng/mL, with a recovery rate of 96.48-97.37%. Consistent with FDA guidelines for bio-analytical method validation, the suggested method was validated. The method was efficiently employed to quantify the studied drug in spiked rat plasma with good accuracy and precision with no significant matrix effects. Furthermore, it was effectively used to investigate the pharmacokinetic behavior of ECT in rats after a single oral dose of 30 mg/kg., (© 2024. The Author(s).)

Aim: JBD0131, a novel anti-multidrug-resistant tuberculosis (MDR-TB) drug, can target and inhibit the synthesis of mycolic acids, which are crucial components of the cell wall of the Mycobacterium tuberculosis complex. To support the results of this clinical trial in healthy subjects, development of a specific and accurate quantification method for detecting JBD0131 and its metabolite DM131 in human plasma is needed. Materials & methods: Samples with prior added stabilizer were pretreated by protein precipitation method and the extracts were subjected to ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). The m/z transitions for the precursor/product ion pairs were 402.1/273 for JBD0131, 333.1/273 for DM131 and 386.1/257 for the internal standard (IS). Results: This method showed good linearity from 1 to 2000 ng/ml for JBD0131 and 0.25 to 500 ng/ml for DM131 and was validated in terms of selectivity, linearity, accuracy, precision, matrix effect, recovery of pretreament and stability. Conclusion: This method was sensitive and specific for measuring the plasma concentrations of JBD0131 and its metabolites. And it was applied for the investigation of the pharmacokinetics of JBD0131 and DM131 in a clinical trial.

Objectives: The objective of this study was to develop and validate an automated solid-phase extraction (SPE) coupled with ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method for the detection of sodium pentachlorophenolate (PCP-Na) residues on cutting boards. Given the potential hazards and environmental persistence of PCP-Na, a sensitive and reliable method is crucial for monitoring its residues in food contact materials to ensure consumer safety., Methods: Wood shavings from cutting boards were extracted using 10% methanol in water, followed by purification using an automated SPE system. The eluent was concentrated, reconstituted, and analyzed by UPLC-MS/MS. An isotope-labeled internal standard was used to mitigate matrix effects, enhancing detection sensitivity. The method was validated by assessing linearity, limit of detection (LOD), limit of quantification (LOQ), recovery rates, and relative standard deviations (RSDs) across various concentration levels., Results: The method demonstrated excellent linearity over a concentration range of 0 to 100 μg/L with a regression equation of Y = 1.035X-0.7771 and an R² of 0.9996. The LOD and LOQ were determined to be 0.4 and 1.0 μg/kg, respectively. Recovery rates ranged from 71.75% to 96.50% with RSDs between 5.19% and 16.66%. When applied to 30 market cutting board samples, PCP-Na residues were detected in 50% of the samples, with concentrations ranging from 0 to 83,990 µg/kg., Conclusion: This study presents a robust UPLC-MS/MS method for the detection of PCP-Na on cutting boards, offering improved sensitivity and simplified sample preparation. The high detection rate in commercial samples underscores the need for stringent monitoring and regulatory measures to mitigate the exposure risk to consumers., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Obeticholic acid (OCA), a semisynthetic bile acid derivative, was approved for its therapeutic use in primary biliary cirrhosis. OCA has a enterohepatic circulation and host-gut microbiota metabolic interaction, which produce various metabolites. Such metabolites, especially structural isomers of OCA, together with the need to achieve idea lower limit of quantitation (LLOQ) with minimum matrix interference, bring about significant difficulties to the bioanalysis of OCA. Herein, by applying a combination of solid-phase extraction (SPE) and ultra-high performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS), we introduced an approach for the bioanalysis of OCA along with its two major metabolites-glyco-OCA (GOA) and tauro-OCA (TOA) in human plasma, the full validation results of which showed excellent performance. The quantitative range is 0.2506 ∼ 100.2 ng/mL for OCA, 0.2500 ∼ 100.0 ng/mL for GOA, as well as 0.1250 ∼ 50.00 ng/mL for TOA, respectively. This method was successfully applied to the pharmacokinetic studies in healthy subjects following administration of OCA tablets., 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.)

Recently, amino acid derivatives gradually gained attention, but studies on N-lactoyl-leucine (Lac-Leu) and N-lactoyl-isoleucine (Lac-Ile) are limited. This study aims to explore the contributions of Lac-Leu and Lac-Ile to soy sauce. Lac-Leu and Lac-Ile were synthesized via enzymatic synthesis method catalyzed by Tgase. The mixed solutions containing Lac-Leu were found to have greater taste improvement than those containing Lac-Ile. Sensory evaluation indicated the sour, bitter, and astringent taste of Lac-Leu in water as well as its kokumi, astringent, and umami-enhancing taste in MSG solution. The taste threshold and umami-enhancing threshold of Lac-Leu measured by TDA and cTDA, respectively, were 0.08 mg/mL and 0.16 mg/mL. Molecular docking of Lac-Leu and Lac-Ile with the kokumi receptor CaSR and the umami receptors T1R1 and T1R3 indicated that Lac-Leu had higher affinities with receptors than Lac-Ile. These findings demonstrated the underlying contribution Lac-Leu made to soy sauce, indicating its potential to improve the flavor quality of soy sauce., Competing Interests: Conflicts of 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 Ltd.)