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Alkali metal-based metal-organic frameworks (MOFs) with permanent porosity are scarce because of their high tendency to coordinate with solvents such as water. However, these MOFs are lightweight and bear gravimetric benefits for gas adsorption related applications. In this study, we present the successful construction of a microporous MOF, designated as HIAM-111, built solely on sodium ions by using an octacarboxylate linker. The structure of HIAM-111 is based on 8-connected Na4 clusters and exhibits a novel topology with an underlying 32,42,8-c net. Remarkably, HAM-111 possesses a robust and highly porous framework with a BET surface area of 1561 m2/g, significantly surpassing that of the previously reported Na-MOFs. Further investigations demonstrate that HIAM-111 is capable of separating C2H2/CO2 and purifying C2H4 directly from C2H4/C2H2/C2H6 with high adsorption capacities. The current work may shed light on the rational design of robust and porous MOFs based on alkali metals.
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PURPOSE: The purpose of this study was to develop an assay for simultaneous determination of lapatinib and its metabolites (N-dealkylated lapatinib and O-dealkylated lapatinib) by ultra-high performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS), and to determine the interaction between shikonin and lapatinib in vitro, in vivo, in silico and its mechanism of action. METHODS: A new UPLC-MS/MS method for the determination of the concentrations of lapatinib and its metabolites was developed. In vivo, Sprague-Dawley (SD) rats were given lapatinib with or without shikonin. In vitro, to study the interaction mechanism, rat liver microsomes (RLMs), human liver microsomes (HLMs) and recombinant human CYP3A4.1 were used for determining enzyme kinetics. Lastly, we used in silico molecular docking to investigate the molecular mechanism of inhibition. RESULTS: The selectivity, precision, accuracy, stability, matrix effect and recovery of UPLC-MS/MS all met the requirements of quantitative analysis of biological samples. Administration of lapatinib combined with shikonin resulted in significantly increased pharmacokinetic parameters (AUC(0-t) and Cmax) of lapatinib, indicating that shikonin increased the exposure of lapatinib in rats. Moreover, in vitro kinetic measurements indicated that shikonin was a time-independent inhibitor, which inhibited the metabolism of lapatinib through a competitive mechanism in RLMs, while noncompetitive inhibition type in both HLMs and CYP3A4.1. Molecular docking analysis further verified the non-competitive inhibition of shikonin on lapatinib in CYP3A4.1. CONCLUSION: We developed an UPLC-MS/MS assay for simultaneous determination of lapatinib and its metabolites. It could be successfully applied to the study of pharmacokinetic interaction of shikonin on the inhibition of lapatinib metabolism in vivo and in vitro. In the end, further studies are needed to determine if such interactions are indeed valid in humans and if the interaction is clinically relevant.
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Citocromo P-450 CYP3A , Naftoquinonas , Espectrometria de Massas em Tandem , Ratos , Humanos , Animais , Lapatinib/metabolismo , Ratos Sprague-Dawley , Cromatografia Líquida , Espectrometria de Massas em Tandem/métodos , Citocromo P-450 CYP3A/metabolismo , Simulação de Acoplamento Molecular , Cromatografia Líquida de Alta Pressão/métodos , Microssomos Hepáticos/metabolismoRESUMO
Luminescent metal-organic frameworks (MOFs) are emerging as one of several promising materials to study light-harvesting and energy-transfer processes. However, it is still a big challenge to tune and direct energy transfer in luminescent MOFs-based light-harvesting system. Herein, a series of new light-harvesting zinc-based luminescent MOFs with seh underlying topology were reported by successfully integrating 2,1,3-benzothiadiazole and its derivative-based carboxylic acids and pyridine-contained linkers into one structure. The strong spectra overlap between the emission and absorption spectra of carboxylic acids and pyridine-type linkers afforded an ideal platform to realize efficient energy transfer from the blue to near-infrared range. This work provides a novel approach to the rational design and synthesis of MOFs-based multicomponent light-harvesting materials with tunable energy transfer to mimic natural photosynthetic processes.
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The development of nanoscaled luminescent metal-organic frameworks (nano-LMOFs) with organic linker-based emission to explore their applications in sensing, bioimaging and photocatalysis is of great interest as material size and emission wavelength both have remarkable influence on their performances. However, there is lack of platforms that can systematically tune the emission and size of nano-LMOFs with customized linker design. Herein two series of fcu- and csq-type nano-LMOFs, with precise size control in a broad range and emission colors from blue to near-infrared, were prepared using 2,1,3-benzothiadiazole and its derivative based ditopic- and tetratopic carboxylic acids as the emission sources. The modification of tetratopic carboxylic acids using OH and NH2 as the substituent groups not only induces significant emission bathochromic shift of the resultant MOFs, but also endows interesting features for their potential applications. As one example, we show that the non-substituted and NH2 -substituted nano-LMOFs exhibit turn-off and turn-on responses for highly selective and sensitive detection of tryptophan over other nineteen natural amino acids. This work sheds light on the rational construction of nano-LMOFs with specific emission behaviours and sizes, which will undoubtedly facilitate their applications in related areas.
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We demonstrate the assembly of a mononuclear metal center, a hexanuclear cluster, and a V-shaped, trapezoidal tetracarboxylate linker into a microporous metal-organic framework featuring an unprecedented 3-nodal (4,4,8)-c lyu topology. The compound, HIAM-302, represents the first example that incorporates both a primary building unit and a hexanuclear secondary building unit in one structure, which should be attributed to the desymmetrized geometry of the organic linker. HIAM-302 possesses optimal pore dimensions and can separate monobranched and dibranched alkanes through selective molecular sieving, which is of significant value in the petrochemical industry.
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Herein, we demonstrate the successful utilization of reticular chemistry as an excellent designing strategy for the deliberate construction of a zirconium-tetracarboxylate metal-organic framework (MOF) inspired by the Olympic rings. HIAM-4017, with an unprecedented (4,8)-c underlying net topology termed jcs, was developed via insightful reconstruction of the rings and judicious design of a nonsymmetric organic linker. HIAM-4017 exhibits high porosity and excellent chemical and thermal stability. Furthermore, excited-state intramolecular proton transfer (ESIPT) was achieved in an isoreticular MOF, HIAM-4018, with a large Stokes shift of 155 nm as a result of introducing the hydroxyl group to the linker skeleton to induce OH···N interactions. Such interactions were analyzed thoroughly by employing the time-dependent density functional theory (TD-DFT). Because of their good thermal and chemical stability, and strong luminescence, nanosized HIAM-4017 and HIAM-4018 were fabricated and used for Cr2O72- detection. Both MOFs demonstrate excellent sensitivity and selectivity. This work represents a neat example of building structure- and property-specific MOFs guided by reticular chemistry.
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Estruturas Metalorgânicas , Teoria da Densidade Funcional , Zircônio , Luminescência , PorosidadeRESUMO
Herein, we demonstrate that linker installation (LI) through postsynthesis is an effective strategy to insert emissive second linkers into single-linker-based metal-organic frameworks (MOFs) to tune the emission properties of multicomponent MOFs. Full-color emission, including white-light emission, can be achieved via such a LI process.
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Metal-organic frameworks (MOFs) exhibit strong potential for applications in molecular adsorption and separation because of their highly tunable structures and large specific surface areas and have also been used for iodine capture. However, most works on MOF-based iodine capture focus on the adsorption capacity while taking little consideration of the capture rate and efficiency. Herein, we report the design of a saddle-shaped tetratopic carboxylic acid containing four thiophene groups (H4COTTBA) and the synthesis of a 4,8-connected flu-type zirconium MOF (HIAM-4014) using this linker. HIAM-4014 exhibits highly efficient iodine capture. The large cagelike pore structure, OH- groups on the unsaturated Zr6 clusters, electron-rich nature of the thiophene group in the linker, and high surface area are all attributed to the tetrahedral geometry of H4COTTBA, which endows HIAM-4014 with a relatively high iodine adsorption capacity of 2.50 g/g within 2 h and an equilibrium adsorption capacity of 2.68 g/g after 5 h. Coupled with a high elution ratio and great recyclability, HIAM-4014 is a good candidate for the efficient removal of waste iodine.
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Metal-organic frameworks (MOFs) demonstrate strong potential for various important applications due to their well tunable structures and compositions through metal and organic linker engineering. As an effective approach, topology evolution by controlling linker conformation has received considerable attention, where solvents and acids have crucial effects on structural formation. However, a systematic study of such effects remains under investigated. Herein, we carried out a methodical study on the topology evolution in Zr-MOFs directed by solvothermal conditions with various combinations of three common solvents and six different acids. As a result, three Zr-MOFs with different topologies, scu (HIAM-4007), scp (HIAM-4008), and csq (HIAM-4009), were obtained using the same Zr6-cluster and tetratopic carboxylate linker, in which structure diversity shows significant influence on their corresponding photoluminescence quantum yields. Further experiments revealed that the acidity of acids and the basicity of solvents strongly influenced the linker conformation in the resultant MOFs, leading to the topology evolution. Such a solvent- and acid-assisted topology evolution represents a general approach that can be used with other tetratopic carboxylate linkers to realize structural diversity. The present work demonstrates an effective structure designing strategy by controlling synthetic conditions, which may prove to be powerful for customized synthesis of MOFs with specific structure and functionality.
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Estruturas Metalorgânicas , Zircônio , Estruturas Metalorgânicas/química , Solventes , Zircônio/químicaRESUMO
Luminescent metal-organic frameworks (LMOFs) demonstrate strong potential for a broad range of applications due to their tunable compositions and structures. However, the methodical control of the LMOF emission properties remains a great challenge. Herein, we show that linker engineering is a powerful method for systematically tuning the emission behavior of UiO-68 type metal-organic frameworks (MOFs) to achieve full-color emission, using 2,1,3-benzothiadiazole and its derivative-based dicarboxylic acids as luminescent linkers. To address the fluorescence self-quenching issue caused by densely packed linkers in some of the resultant UiO-68 type MOF structures, we apply a mixed-linker strategy by introducing nonfluorescent linkers to diminish the self-quenching effect. Steady-state and time-resolved photoluminescence (PL) experiments reveal that aggregation-caused quenching can indeed be effectively reduced as a result of decreasing the concentration of emissive linkers, thereby leading to significantly enhanced quantum yield and increased lifetime.
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The transport of hydrated ions across nanochannels is central to biological systems and membrane-based applications, yet little is known about their hydrated structure during transport due to the absence of in situ characterization techniques. Herein, we report experimentally resolved ion dehydration during transmembrane transport using modified in situ liquid ToF-SIMS in combination with MD simulations for a mechanistic reasoning. Notably, complete dehydration was not necessary for transport to occur across membranes with sub-nanometer pores. Partial shedding of water molecules from ion solvation shells, observed as a decrease in the average hydration number, allowed the alkali-metal ions studied here (lithium, sodium, and potassium) to permeate membranes with pores smaller than their solvated size. We find that ions generally cannot hold more than two water molecules during this sterically limited transport. In nanopores larger than the size of the solvation shell, we show that ionic mobility governs the ion hydration number distribution. Viscous effects, such as interactions with carboxyl groups inside the membrane, preferentially hinder the transport of the mono- and dihydrates. Our novel technique for studying ion solvation in situ represents a significant technological leap for the nanofluidics field and may enable important advances in ion separation, biosensing, and battery applications.
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Transporte de Íons , Lítio/química , Potássio/química , Sódio/química , Água/química , Dispositivos Lab-On-A-Chip , Membranas Artificiais , Microfluídica/instrumentação , Nylons/química , ViscosidadeRESUMO
While limited choice of emissive organic linkers with systematic emission tunability presents a great challenge to investigate energy transfer (ET) over the whole visible light range with designable directions, luminescent metal-organic frameworks (LMOFs) may serve as an ideal platform for such study due to their tunable structure and composition. Herein, five Zr6 cluster-based LMOFs, HIAM-400X (X=0, 1, 2, 3, 4) are prepared using 2,1,3-benzothiadiazole and its derivative-based tetratopic carboxylic acids as organic linkers. The accessible unsaturated metal sites confer HIAM-400X as a pristine scaffold for linker installation. Six full-color emissive 2,1,3-benzothiadiazole and its derivative-based dicarboxylic acids (L) were successfully installed into HIAM-400X matrix to form HIAM-400X-L, in which the ET can be facilely tuned by controlling its direction, either from the inserted linkers to pristine MOFs or from the pristine MOFs to inserted linkers, and over the whole range of visible light. The combination of the pristine MOFs and the second linkers via linker installation creates a powerful two-dimensional space in tuning the emission via ET in LMOFs.
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Hydroxyl radical (â¢OH) can hydroxylate or dehydrogenate organics without forming extra products and is thereby expediently applied in extensive domains. Although it can be efficiently produced through single-electron transfer from transition-metal-containing activators to hydrogen peroxide (H2O2), narrow applicable pH range, strict activator/H2O2 ratio requirement, and byproducts that are formed in the mixture with the background matrix necessitate the need for additional energy-intensive up/downstream treatments. Here, we show a green Fenton process in an electrochemical cell, where the electro-generated atomic H* on a Pd/graphite cathode enables the efficient conversion of H2O2 into â¢OH and subsequent degradation of organic pollutants (80% efficiency). Operando liquid time-of-fight secondary ion mass spectrometry verified that H2O2 activation takes place through a transition state of the Pd-H*-H2O2 adduct with a low reaction energy barrier of 0.92 eV, whereby the lone electron in atomic H* can readily cleave the peroxide bridge, with â¢OH and H2O as products (ΔGr = -1.344 eV). Using H+ or H2O as the resource, we demonstrate that the well-directed output of H* determines the pH-independent production of â¢OH for stable conversion of organic contaminants in wider pH ranges (3-12). The research pioneers a novel path for eliminating the restrictions that are historically challenging in the traditional Fenton process.
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Radical Hidroxila , Poluentes Químicos da Água , Eletrodos , Peróxido de Hidrogênio , Concentração de Íons de Hidrogênio , OxirreduçãoRESUMO
A pore confined liquid-vacuum interface was created in liquid secondary ion mass spectrometry analysis in order to study the charge transfer in electrochemical reactions. The interfacial processes such as the critical diameter, influence of aperture properties on the morphology of the liquid-vacuum interface, pressure field, concentration field, and electric field were revealed by finite element simulation. The correlation between numerical study of the chemical changes at the electrode-electrolyte interface and experimental results during the dynamic potential scan was built successfully. Better understanding of these interfacial processes could promote further applications of liquid secondary ion mass spectrometry in energy storage and electrochemical catalysis.
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Tyrosinase (TYR) which can catalyze the oxidation of catechol is recognized as a significant biomarker of melanocytic lesions, thus developing powerful methods for the determination of TYR activity is highly desirable for the early diagnosis of melanin-related diseases, including melanoma. Herein, we develop a novel portable and recyclable surface-enhanced Raman scattering (SERS) sensor, prepared by assembling gold nanoparticles and p-thiol catechol ( p-TC) on an ITO electrode, for detecting TYR activity via the SERS spectral variation caused by the conversion of p-TC into its corresponding quinone under TYR catalysis. The developed SERS sensor has a rapid response to TYR within 1 min under the optimized conditions and shows high selectivity for TYR with the detection limit at 0.07 U/mL. Importantly, this SERS sensor can be easily regulated by applying negative voltage to achieve circular utilization, favoring the automation of SERS detection. Furthermore, the presented recyclable SERS sensor can perform well on both the determination of TYR activity in serum and the assessment of TYR inhibitor, demonstrating huge potential in the sensitive, selective, and facile detection of TYR activity for disease diagnosis and drug screening related with TYR.
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Técnicas Eletroquímicas/instrumentação , Ouro , Nanopartículas Metálicas/química , Monofenol Mono-Oxigenase/metabolismo , Reciclagem , Técnicas Biossensoriais/métodos , Limite de Detecção , Análise Espectral Raman/métodosRESUMO
Tracking detailed hand motion is a fundamental research topic in the area of human-computer interaction (HCI) and has been widely studied for decades. Existing solutions with single-model inputs either require tedious calibration, are expensive or lack sufficient robustness and accuracy due to occlusions. In this study, we present a real-time system to reconstruct the exact hand motion by iteratively fitting a triangular mesh model to the absolute measurement of hand from a depth camera under the robust restriction of a simple data glove. We redefine and simplify the function of the data glove to lighten its limitations, i.e., tedious calibration, cumbersome equipment, and hampering movement and keep our system lightweight. For accurate hand tracking, we introduce a new set of degrees of freedom (DoFs), a shape adjustment term for personalizing the triangular mesh model, and an adaptive collision term to prevent self-intersection. For efficiency, we extract a strong pose-space prior to the data glove to narrow the pose searching space. We also present a simplified approach for computing tracking correspondences without the loss of accuracy to reduce computation cost. Quantitative experiments show the comparable or increased accuracy of our system over the state-of-the-art with about 40% improvement in robustness. Besides, our system runs independent of Graphic Processing Unit (GPU) and reaches 40 frames per second (FPS) at about 25% Central Processing Unit (CPU) usage.
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A pretreatment method named tablet-effervescence-assisted dissolved carbon flotation was introduced for the determination of four triazole fungicides in environmental water. In this method, the use of effervescent tablet composed of nontoxic sodium carbonate and sodium dihydrogen phosphate could generate CO2 in situ to assist the dispersion of extraction solvent and to accelerate mass transfer of target analytes. In addition, the simple phase separation simply based on the rising of low-density organic solvent from the aqueous phase was applied rather than the application of apparatus, which demonstrated the potential for on-site extraction in the field. The experimental variables, including the composition of effervescent tablets, amount of effervescent tablets, types and volume of extraction solvent, were investigated. Under the optimized conditions, the method showed good linearity for myclobutanil, tebuconazole, epoxiconazole, and difenoconazole in the range of 1-100 µg/L. The limits of detection and the limits of quantification were within the range of 0.15-0.26 and 0.49-0.86 µg/L, respectively. The obtained correlation coefficients varied from 0.997 to 0.999, and suitable enrichment factors were 422-589. The recoveries were 82.5-112.9% with relative standard deviations of 4.7-13.5%.
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Fungicidas Industriais/isolamento & purificação , Cromatografia Gasosa-Espectrometria de Massas , Triazóis/isolamento & purificação , Carbono , Cromatografia Líquida de Alta Pressão , Comprimidos , ÁguaRESUMO
Apixaban is an oral anticoagulant that directly inhibits the target Factor Xa (FXa). In this study, we focused on the in vivo and in vitro effects of adagrasib and asciminib on apixaban metabolism, to discover potential drug-drug interactions (DDI) and explore their inhibitory mechanisms. The levels of apixaban and its metabolite, O-desmethyl-apixaban (M2), were determined by ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS). In vitro evaluation, the maximum half inhibitory concentration (IC50) of adagrasib in rat liver microsomes (RLM) and human liver microsomes (HLM) against apixaban was 7.99 µM and 117.40 µM, respectively. The IC50 value of asciminib against apixaban in RLM and HLM was 4.28 µM and 18.42 µM, respectively. The results of the analysis on inhibition mechanisms showed that adagrasib inhibited the metabolism of apixaban through a non-competitive mechanism, while asciminib inhibited the metabolism of apixaban through a mixed mechanism. Moreover, the interaction of apixaban with adagrasib and asciminib in Sprague-Dawley (SD) rats was also investigated. It was found that the pharmacokinetic characteristics of apixaban were significantly changed when combined with these two antitumor drugs, where AUC(0-t), AUC(0-∞), t1/2, Tmax, and Cmax were increased, while CLz/F was significantly decreased. But both drugs did not appear to affect the metabolism of M2 in a significant way. Consistent results from in vitro and in vivo demonstrated that both adagrasib and asciminib inhibited the metabolism of apixaban. It provided reference data for the future clinical individualization of apixaban.
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Antineoplásicos , Microssomos Hepáticos , Pirazóis , Piridonas , Ratos Sprague-Dawley , Animais , Pirazóis/farmacologia , Pirazóis/metabolismo , Piridonas/farmacologia , Piridonas/farmacocinética , Humanos , Microssomos Hepáticos/metabolismo , Ratos , Masculino , Antineoplásicos/farmacologia , Interações Medicamentosas , Espectrometria de Massas em Tandem , Inibidores do Fator Xa/farmacologia , Inibidores do Fator Xa/farmacocinética , Fenilacetatos , TiofenosRESUMO
Dabrafenib is a BRAF inhibitor that has been demonstrated to be efficacious in the treatment of melanoma and non-small-cell lung cancer patients with BRAF V600E mutations. The objective of this study was to investigate the effects of 51 traditional Chinese medicines on the metabolism of dabrafenib and to further investigate the inhibitory effect of imperatorin. The quantification of dabrafenib and its metabolite hydroxy-dabrafenib was carried out using a sensitive, rapid, and accurate assay method based on ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS). The results of in vitro experiments showed that 20 drugs inhibited the metabolism of dabrafenib by more than 80 %. In a further study of imperatorin on dabrafenib, the half-maximal inhibitory concentration (IC50) values of imperatorin on dabrafenib were 0.22 µM and 3.68 µM in rat liver microsomes (RLM) and human liver microsomes (HLM), respectively, while the inhibition mechanisms were non-competitive and mixed type inhibition, respectively. The results of in vivo experiments demonstrated that in the presence of imperatorin, the AUC(0-t), AUC(0-∞), Cmax, and Tmax of dabrafenib were increased by 2.38-, 2.26-, 1.05-, and 6.10-fold, respectively, while CLz/F was decreased by 67.9 %. In addition, Tmax of hydroxy-dabrafenib was increased by 1.4-fold. The results of the research showed that imperatorin had a consistent inhibitory effect on dabrafenib in vitro and in vivo. When the concurrent use of dabrafenib and imperatorin is unavoidable, clinicians should closely monitor for potential adverse events and make timely adjustments to the administered dosage.
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Furocumarinas , Imidazóis , Microssomos Hepáticos , Oximas , Ratos Sprague-Dawley , Oximas/farmacologia , Imidazóis/farmacologia , Imidazóis/metabolismo , Animais , Furocumarinas/farmacologia , Furocumarinas/metabolismo , Microssomos Hepáticos/metabolismo , Humanos , Ratos , Masculino , Espectrometria de Massas em Tandem , Cromatografia Líquida de Alta PressãoRESUMO
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 0.1â¯% 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 2-50â¯ng/mL and 1-20â¯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 (IC50) value of 10.54⯵M and 47.64⯵M, 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 Cmax of fuzuloparib and a significant decrease in CLz/F. Moreover, the metabolite SHR165202 showed significant increases in AUC(0-t), AUC(0-∞), Tmax and Cmax and a significant decrease in CLz/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.