Fluoro Phenyl Research Articles

Synthesis of Novel Fluoro Phenyl Triazoles Via Click Chemistry with or without Microwave Irradiation and their Evaluation as Anti-proliferative Agents in SiHa Cells.

Perform the synthesis of novel fluoro phenyl triazoles via click chemistry with or without microwave irradiation and their evaluation as anti-proliferative agents in SiHa cells. Triazoles are heterocyclic compounds containing a five-member ring with two carbon and three nitrogen atoms. They are of great importance since many of them have shown to have biological activity as antifungal, antiviral, antibacterial, anti-HIV, anti-tuberculosis, vasodilator, and anticancer agents. Synthesize novel fluoro phenyl triazoles via click chemistry and evaluate their antiproliferative activity. First, several fluorophenyl azides were prepared. Reacting these aryl azides with phenylacetylene in the presence of Cu(I) catalyst, the corresponding fluoro phenyl triazoles were obtained by two methodologies, stirring at room temperature and under microwave irradiation at 40ºC. In addition, their antiproliferative activity was evaluated in cervical cancer SiHa cells. Fluoro phenyl triazoles were obtained within minutes by means of microwave irradiation. The compound 3f, containing two fluorine atoms next to the carbon connected to the triazole ring, was the most potent among the fluoro phenyl triazoles tested in this study. Interestingly, the addition of a fluorine atom to the phenyl triazole structure in a specific site increases its antiproliferative effect as compared to parent phenyl triazole 3a without a fluorine atom. Several fluoro phenyl triazoles were obtained by reacting fluoro phenyl azides with phenylacetylene in the presence of copper sulphate, sodium ascorbate and phenanthroline. Preparation of these triazoles with MW irradiation represents a better methodology since they are obtained within minutes and higher yields of cleaner compounds are obtained. In terms of biological studies, the proximity between fluorine atom and triazole ring increases its biological activity.

DEVELOPMENT AND VALIDATION OF AN LC-MS/MS METHOD FOR THE DETERMINATION OF TENOFOVIR AND EMTRICITABINE

Objective: Therapeutic drug monitoring of tenofovir and emtricitabine, two commonly used antiretroviral drugs, is important to maximize effectiveness while minimizing side effects. Materials: A Liquid Chromatography-Mass spectrometry (LC-MS/MS) method was developed to quantify tenofovir and emtricitabine in human plasma samples. The method involves a simple solid phase extraction procedure followed by liquid chromatography separation using a Penta Fluoro Phenyl (PFP) column with a Phenomenex C18 column and a mobile phase of ammonium formate, acetonitrile, and methanol, achieving separation in under 4 min. Results: The method showed good accuracy, low limits of quantification, adequate recovery, minimal matrix effects, and specificity. Analyte stability under multiple storage conditions was demonstrated. Conclusion: The validated LC-MS/MS method provides a reliable tool for therapeutic drug monitoring and pharmacokinetic studies of anti-Human Immuno-deficiency Virus (HIV) regimens. The assay can be applied to large populations, especially in resource-poor settings, to help individualize dosing and improve clinical outcomes while reducing toxicity.

Pyrazole Scaffold: Potential PTP1B Inhibitors for Diabetes Treatment.

The overexpression of the Protein Tyrosine Phosphatase 1B (PTP1B), a key role in the development of insulin resistance, diabetes (T2DM) and obesity, seems to have a substantial impact as a negative regulator of the insulin and leptin signaling pathways. Therefore, inhibiting PTP1B is a prospective therapeutic approach for the treatment of diabetes and obesity. However, the pyrazole scaffold is expected to be of significant pharmaceutical interest due to its broad spectrum of pharmacological actions. This study aims to focus on the significance of pyrazole scaffold in medicinal chemistry, the impact of PTP1B in diabetes and the therapeutic approach of pyrazole scaffold to treat T2DM. A comprehensive analysis of the published literature in several pharmaceutical and medical databases, such as the Web of Science (WoS), PubMed, ResearchGate, ScienceDirect etc., were indeed successfully completed and classified accordingly. Results: As reviewed, the various derivatives of the pyrazole scaffold exhibited prominent PTP1B inhibitory activity. The result showed that derivatives of oxadiazole and dibenzyl amine, chloro substituents, 1, 3-diaryl pyrazole derivatives with rhodanine-3-alkanoic acid groups, naphthalene and also 1, 3, 5-triazine-1H-pyrazole-triazolothiadiazole derivatives, octyl and tetradecyl derivative, indole- and N-phenylpyrazole-glycyrrhetinic acid derivatives with trifluoromethyl group, 2,3-pyrazole ring-substituted-4,4-dimethyl lithocholic acid derivatives with 4- fluoro phenyl substituted and additional benzene ring in the pyrazole scaffold significantly inhibits PTP1B. In silico study observed that pyrazole scaffold interacted with amino acid residues like TYR46, ASP48, PHE182, TYR46, ALA217 and ILE219. Diabetes is a metabolic disorder that elevates the risk of mortality and severe complications. PTP1B is a crucial component in the management of diabetes and obesity. As a result, PTP1B is a promising therapeutic target for the treatment of T2DM and obesity in humans. We concluded that the pyrazole scaffold has prominent inhibitory potential against PTP1B.

Semiconducting CdS quantum dots as a guest in a four ring bent-core nematic medium: modified dielectric and elastic properties

The nematic phase of the bent-core family proves to be particularly fascinating due to its distinct properties in comparison to its calamitic counterpart. Here we revealed after the dispersion of semiconducting CdS QD an achiral unsymmetrical (4′-fluoro phenyl azo) phenyl-4-yl 3-[N-(4′-n-hecyloxy two hydroxybenzylidene)amino]-2-methylbenzoate (6-2M-F) a bent-core nematic (BCN) liquid-crystalline medium made of bent-shaped molecules with short cores and low bend angles. These molecules are on the cusp between conventional bent-core molecules and rod-like molecules, with characteristics somewhere in between, resembling hockey sticks. The threshold voltage dielectric permittivity and elastic constants of pure BCN have been considerably influenced by semiconductor nanoparticles. The threshold voltage of nano-disperse BCN has decreased with QD doping, and we know that the low operation voltage is one of the key considerations in the development of mobile liquid crystal display technology. Similar to other BCNs with smectic-like clusters previously described, the elastic anisotropy for 6-2M-F is negative; however, the insertion of CdS QDs causes the anisotropy to become very positive (bend elastic constant > splay elastic constant ). While the parallel component of permittivity has declined with doping, the perpendicular component of permittivity has increased, leading to a considerable reduction in dielectric anisotropy in the nanocomposite, which implies the effect on nematic ordering due to the interaction between CdS QDs and the LC molecules.

Synthesis and Evaluation of Anticancer activity of some new 3(2h)-one pyridazinone derivatives by Molecular Docking Studies

The present research aims to synthesize new series of 3(2h)-one pyridazinone derivatives with a potential anti-oxidant activity. All the compounds were synthesized by the esterification reaction of 2-(4- Fluoro Phenyl)--butyric acid with sulphuric acid and ethanol followed by hydrazine hydrate to give substituted hydrazides and then hydrazone with substituted ketons, which are cyclized with aldehyde substitutes to give the [5-(2,5-Dichloro-phenyl)-2-oxo-3,4-dihydro-2H-pyridin-1-yl]-acetic acid(4-4chloro-benzylidene)-hydrazide derivatives. Structure of all derivatives was confirmed by Fourier transform infrared spectroscopy (FT-IR) and Nuclear magnetic resonance (NMR) spectroscopy. All these compounds were demonstrated for in-vitro anti oxidant activity by using DPPH radical scavenging activity and hydrogen peroxide scavenging activity. Molecular Docking was carried out by cyclin dependent kinase protein and DNA-hexamer ATGCAT. Molecular docking studies of derivatives were carried out by AutoDock Vina molecular docking software. All the results were calculated by PaDEL software. Results of antioxidant activity revealed that all compounds are potent antioxidants at a concentration of 50µg/ml.

Building 2D classification models and 3D CoMSIA models on small-molecule inhibitors of both wild-type and T790M/L858R double-mutant EGFR.

Epidermal growth factor receptor (EGFR) has received widespread attention because it is an important target for anticancer drug design. Mutations in the EGFR, especially the T790M/L858R double mutation, have made cancer treatment more difficult. We herein built the structure-activity relationship models of small-molecule inhibitors on wild-type and T790M/L858R double-mutant EGFR with a whole dataset of 379 compounds. For 2D classification models, we used ECFP4 fingerprints to build support vector machine and random forest models and used SMILES to build self-attention recurrent neural network models. Each of all six models resulted in an accuracy of above 0.87 and the Matthews correlation coefficient value of above 0.76 on the test set, respectively. We concluded that inhibitors containing anilinoquinoline and methoxy or fluoro phenyl are highly active against wild EGFR. Substructures such as anilinopyrimidine, acrylamide, amino phenyl, methoxy phenyl, and thienopyrimidinyl amide appeared more in highly active inhibitors against double-mutant EGFR. We also used self-organizing map to cluster the inhibitors into six subsets based on ECFP4 fingerprints and analyzed the activity characteristics of different scaffolds in each subset. Among them, three datasets, which are based on pteridin, anilinopyrimidine, and anilinoquinoline scaffold, were selected to build 3D comparative molecular similarity analysis models individually. Models with the leave-one-out coefficient of determination (q2) above 0.65 were selected, and five descriptor types (steric, electrostatic, hydrophobic, donor, and acceptor) were used to study the effects of side chains of inhibitors on the activity against wild-type and mutant-type EGFR.

Synthesis and Identification and Biological Studies of New Azo Dyes Derived from Imidazole and their Chelate Complexes

Anew azo ligand (E)-2-((4- fluoro phenyl)diazenyl)-4,5-bis(4-methoxy phenyl)-1H-imidazolehas beensynthesized from coupling 4,5-bis(4-methoxyphenyl)imidazole with para-chloro-anline. The structures ofthe new ligand and their transition metal complexes ware investigated and characterized using differentphysicochemical studies as elemental analysis, IR spectra, 1HNMR,, UV-Vis spectra, mass spectra, Molarconductance ,and magnetic susceptibility .The complexes were found to have the general formula [ML2Cl2].H2O where M = Co(II), Ni(II), Cu(II) ,Mn(II),and Fe(II), [MLCl2].H2Owhere M=Zn(II),Cd(II),Hg(II), andPd(II). The IR results demonstrate that the co-ordination sites are the azomethine nitrogen of the imidazolering and azo nitrogen atom of the azo ligand. The electronic spectral and magnetic measurement dataindicate that the complexes exhibit octahedral geometry,except the Zn(II),Cd(II),andHg(II) complexessuggest tetrahedral and Pd(II) a square planar geometry.The cytotoxicity of Pd(II) complex on human LungCancer (SCLC) and normal cells.

Linear solvation energy relationships in the determination of phospholipids by supercritical fluid chromatography

The separation of phospholipids was studied using supercritical fluid chromatography. The 2-ethylpyridine (2-EP), hybrid fluoro-phenyl (FP), C18, 2-picolylamine (2-PIC), 1-aminoanthracene (1-AA), DIOL and ethylene bridged hybrid (BEH) were used as stationary phases. Methanol with 0.1% formic acid was used as a co-solvent. For the first time, the linear solvation energy relationships (LSER) were used to evaluate the retention mechanism of phospholipid by SFC. Based on Abrahamʼs equation, the stationary phases were classified according to their interaction properties. The retention mechanism of phospholipid at SFC is based on different interactions depend on columns type. Moreover, structural descriptors of the target compounds were used to describe their chromatographic retention behavior under the optimized SFC conditions.

Evaluation of [18F]F-DPA as a target for TSPO in head and neck cancer under normal conditions and after radiotherapy

BackgroundMany malignant tumours have increased TSPO expression, which has been related to a poor prognosis. TSPO-PET tracers have not comprehensively been evaluated in peripherally located tumours. This study aimed to evaluate whether N,N-diethyl-2-(2-(4-([18F]fluoro)phenyl)-5,7-dimethylpyrazolo[1,5-a]pyrimidin-3-yl)acetamide ([18F]F-DPA) can reflect radiotherapy (RT)-induced changes in TSPO activity in head and neck squamous cell carcinoma (HNSCC).MethodsRT was used to induce inflammatory responses in HNSCC xenografts and cells. [18F]F-DPA uptake was measured in vivo in non-irradiated and irradiated tumours, followed by ex vivo biodistribution, autoradiography, and radiometabolite analysis. In vitro studies were performed in parental and TSPO-silenced (TSPO siRNA) cells. TSPO protein and mRNA expression, as well as tumour-associated macrophages (TAMs), were also assessed.ResultsIn vivo imaging and ex vivo measurement revealed significantly higher [18F]F-DPA uptake in irradiated, compared to non-irradiated tumours. In vitro labelling studies with cells confirmed this finding, whereas no effect of RT on [18F]F-DPA uptake was detected in TSPO siRNA cells. Radiometabolite analysis showed that the amount of unchanged [18F]F-DPA in tumours was 95%, also after irradiation. PK11195 pre-treatment reduced the tumour-to-blood ratio of [18F]F-DPA by 73% in xenografts and by 88% in cells. TSPO protein and mRNA levels increased after RT, but were highly variable. The proportion of M1/M2 TAMs decreased after RT, whereas the proportion of monocytes and migratory monocytes/macrophages increased.Conclusions[18F]F-DPA can detect changes in TSPO expression levels after RT in HNSCC, which does not seem to reflect inflammation. Further studies are however needed to clarify the physiological mechanisms regulated by TSPO after RT.

Synthesis and Properties of N,N′-Disubstituted Ureas and Their Isosteric Analogs Containing Polycyclic Fragments: VI. N-[Fluoro(chloro)phenyl]-N′-(4,7,7-trimethyl-3-oxo-2-oxabicyclo[2.2.1]heptan-1-yl)ureas

The reaction of (S)-(–)-1-isocyanato-4,7,7-trimethyl-2-oxabicyclo[2.2.1]heptan-3-one with fluoro- and chloro-substituted anilines afforded a series of N,N′-disubstituted ureas containing a natural lipophilic camphanic acid moiety in 42–75% yield. The synthesized compounds are promising as inhibitors of human soluble epoxide hydrolase.

Synthesis and Properties of N,N′-Disubstituted Ureas and Their Isosteric Analogs Containing Polycyclic Fragments: II. N-(4-Oxoadamantan-1-yl)-N′-[fluoro(chloro)phenyl]ureas

A series of N-(4-oxoadamantan-1-yl)-N′-[fluoro(chloro)phenyl]ureas have been synthesized in 27–73% yields by reaction of 1-isocyanatoadamantan-4-one with fluoro- and chlorosubstituted anilines. The products are promising as human soluble epoxide hydrolase inhibitors.

Development of LC-MS and LC-MS/MS Methods for Free Asparagine in Grains

New analytical methods for the determination of free asparagine （Asn）, which is a precursor of acrylamide, in grains were developed using LC-MS and LC-MS/MS. Asn was extracted from a sample with 5％ （w/v） aqueous trichloroacetic acid solution, appropriately diluted with 0.1％ （v/v） formic acid solution, and then analyzed by LC-MS or LC-MS/MS. HPLC separation was performed by isocratic elution on a Penta Fluoro Phenyl （PFP） column using 0.1％ （v/v） formic acid and acetonitrile mixture as the mobile phase. The calibration curve was linear in the range of 0.005-0.1 μg/mL. The mean recoveries from potato starch, non-glutinous rice flour and whole wheat flour ranged from 95.4 to 100.9％, repeatability （RSD） ranged from 0.9 to 6.0％, and within-laboratory reproducibility （RSDwr） ranged from 2.8 to 7.1％. Limits of quantitation （LOQs） were 7 mg/kg for potato starch, and 5 mg/kg for non-glutinous rice flour. In addition, an inter-laboratory study was performed in 10 laboratories using 5 kinds of grains （non-glutinous brown rice flour, corn flour, strong flour, whole wheat flour, and whole rye flour）, which naturally contained free asparagine. The HORRATR values ranged from 0.4 to 1.0. These results are within the range of the procedural manual of the Codex Alimentarius Commission, confirming the effectiveness of the developed procedures.

Experimental and theoretical spectroscopic studies in relation to molecular structure investigation of para chloro, para fluoro and para nitro maleanilinic acids

In the present work novel para chloro, para fluoro and para nitro maleanilic acid derivatives were prepared and investigated using FT-IR, thermal analyses (TA) measurements (TGA/DTG and DTA) in comparison with mass spectral (MS) fragmentation at 70 eV. The crystallographic structures of studied compounds were investigated by X-ray diffraction (XRD). The vibrational frequencies and the corresponding normal modes were evaluated at the optimized geometry. Vibrational modes were analyzed using GAUSSVIEW software. Experimental FT-IR and Raman spectra of the three newly prepared derivatives, namely, (E) – oxo -4- ((4- nitro phenyl) amino)-4- oxobut-2-enoic acid (p-NMA), (E) -4- ((4- chloro phenyl)amino)-4- oxobut -2- enoic acid (p-ClMA), (E) -4- ((4- fluoro phenyl) amino)- 4- oxobut -2- enoic acid (p-FMA) were compared with the theoretically calculated one. FT-IR and the observed vibrational frequencies were assigned; thermal analysis and mass spectrum measurements of the maleanilic acid derivatives were recorded and discussed. The computational calculations were carried out by DFT - B3LYP method with 6-311++G(d,p) basis sets and the corresponding results were tabulated. The alternations of structures of p-FMA, p-ClMA and p-NMA due to the subsequent substitutions were investigated. This correlation between experimental and theoretical calculations provided a good confirmation of the proposed structures of the newly prepared compounds. The derivatives were found to be highly effective against Hepatocellular carcinoma cells > Breast carcinoma cells > colon carcinoma cells. It was recognized, that cancer cells over expression promotes tumorigenic functions; can be suppressed by p-NMA > p-FMA > p-ClMA inhibitors.

SPMMTE and Q-TOF–UPLC–MS for monitoring of atenolol and atorvastatin in human plasma using pentafluoro phenyl column

ABSTRACTIron nanocomposite adsorbent was prepared by green technology with 90% yield. The prepared iron nanocomposite adsorbent was used in solid-phase micromembrane tip extraction (SPMMTE) sample preparation technique. Analysis of atenolol and atorvastatin was performed in human plasma using SPMMTE and Q-TOF–UPLC–MS methods. New generation Acquity UPLC HSS penta fluoro phenyl (2.1 × 75 mm2; 1.8 µm) column was used with acetonitrile–0.1% formic acid in water (50:50 v/v) as mobile phase. The flow rate was 0.2 mL min−1 with electrospray mass detection. The limits of detection were 0.2 and 0.4 ng active mass for atenolol and atorvastatin, while the limits of quantification were 1.0 and 2.0 ng active mass, respectively. The values of the retention times were 3.224 and 3.907 for atorvastatin and atenolol. The values of the separation and resolution factors were 1.31 and 1.71, respectively. The peaks were sharp with base lined separation within 4.2 min. The developed SPMMTE and Q-TOF–UPLC–MS methods were reproducible, fast, precise, robust, rugged, and economic for the analyses of atenolol and atorvastatin in human plasma. The reported methods can be applied for monitoring of the reported drugs at trace level.

Development and validation of an ultra-performance liquid chromatography method for the determination of bis(2,4-di-tert-butylphenyl)phosphate and related extractable compounds from single-use plastic films

A UPLC-UV method is described for the detection of bDtBPP and related breakdown compounds of Irgafos 168 from single-use bioprocessing bag films using a CSH (charged surface hybrid) fluoro phenyl column and UV detection at 220nm. The method limits of detection were between 16μgL‐1 and 60μgL‐1, repeatability was %RSD≤1.8 and linearity was R2≥0.9992. The method was applied to an extractables and leachables test of three single-use bioprocessing bag films. bDtBPP and oxidised Irgafos were detected from all three films in the extractables study, but not in the leachables study. A comparison of whole bag and small scale film extractions demonstrated that the small scale extractions were more suitable for finding concentration per area of film and/or estimating total load of extractables in the entire bag. The feasibility of upstream monitoring of extractable and leachable compounds with the Waters PATROL UPLC System via a Flownamics® sampling probe was also tested with cell growth medium spiked with bDtBPP. bDtBPP was only detected in at-line injections or online injections when the probe membrane was removed indicating that with the current sampling interface, monitoring of extractables and/or leachables is limited to at-line sampling.

Synthesis and Biological Evaluation of 2-Aryl - 6, 7-Difluorophenyl-1,3,4- Oxadiazolo (3,2-a) (1,3,5)-Triazine-5-(6H,7H)-Thiones

2-Aryl-6,7-difluorofenyl-1,3,4-oxadiazolo (3,2-a) (1,3,5)- triazine-5-(6H,7H)- thiones (2a-j) have been orchestrated by the cyclo expansion of para-fluorophenyl 4 –fluoro phenyl isothiocynate and 2-(4-fluorobenzylidine) to (1a-j) 2-amino - 5-phenyl-1,3,4-oxadiazole in dry toluene all the integrated compounds were very much described by their elemental analysis and spectral data. The integrated compounds have been screened for their antifungal action against Phytophthora infestans and Colletotrichum falcatum. Results demonstrated that greatest antifungal activity was appeared by the compounds 2b, 2c, 2g and 2h. These compounds demonstrated 99%, 98%, 99% and 97% hindrance of Phytophthora infestans and 97%, 96%, 98% and 97% Colletotrichum falcatum at 1000 ppm respectively.

Influence of m-fluorine substituted phenylene spacer dyes in dye-sensitized solar cells

A series of new organic dyes based on fluorine substituted phenyl moiety, used as a π-linker in various dyes, were designed and synthesized for dye sensitized solar cell (DSSC) application. These dyes share same anchoring group (Cyano acrylic acid) with different donors such as carbazole, thiopene substituted carbazole, triphenylamine and phenothiazine moieties. For effective electron flow, the dyes were incorporated with novel D-π-A or D-A-A framework. The optical, electrochemical, time-resolved photoluminescence (TRPL) spectra and photovoltaic properties of the dyes were carefully studied. The results reveal that without addition of any co-adsorbent, among all fluoro-phenyl spacer dyes, the Cz-dye showed highest open circuit voltage (Voc), short circuit current (Jsc) and exhibited enhanced PCE value of 4.2 (±0.2) %, due to the deeper HOMO level of dye, planarity of backbone with better charge transfer occurring form D to A. The optimization calculations for the geometries of all the dyes with fluoro phenyl substituted π-linkers were ascertained by Density functional theory (DFT) using B3LYP/631G (d,p) basis set.

Elastic constants, viscosity and dielectric properties of bent-core nematic liquid crystals doped with single-walled carbon nanotubes

ABSTRACTSingle-walled carbon nanotubes (SWCNTs) are dispersed in (4’-fluoro phenyl azo) phenyl-4-yl 3-[N-(4’-n-hecyloxy 2-hydroxybenzylidene)amino]-2-methylbenzoate (6–2M-F) a bent-core nematic (BCN) liquid crystalline medium composed of bent-shaped molecules with short core, reduced bend angle possessing polar fluoro substituent in longitudinal direction and methyl group in bent direction. Such molecules are at the borderline of typical bent-core and rod-like molecules resembling hockey stick shape with intermediate properties. The elastic anisotropy is negative for 6–2M-F (bend elastic constant K33 < splay elastic constant K11); similar to other BCNs reported earlier with smectic-like clusters; but turns to high positive (K33 > K11) value by insertion of SWCNT (concentration ≥0.05 wt.%) in 6–2 M-F. The ratio of K33/K11 becomes comparable to the calamitic liquid crystals (LCs) in doped system. Dielectric anisotropy increases in the nanocomposite implying enhanced nematic ordering due to π–π electron interaction between CNTs and the LC molecules. Threshold voltage at first increases and then decreases with increasing CNT concentration owing to the respective variations in splay viscosity of the system. The present study demonstrated the interaction of SWCNTs with BCN molecules and reveals significant modifications in viscoelastic, dielectric and ionic properties of the host.

Synthesis of 1-organyl-1-(trimethylsiloxy)-2-(dimethylamino)ethenes and new hypervalent silicon compounds based thereon

1-Organyl-1-(trimethylsiloxy)-2-(dimethylamino)ethenes were synthesized for the first time, and their reactions with trichloro(methyl)silane and trifluoro(phenyl)silane afforded silicon bis-chelates, methylbis-[2-(dimethylamino)-1-(organyl)ethenolato-N,O]siliconium chlorides and bis[1-(dimethylamino)-3,3-dimethylbut-1-en-2-olato-N,O]fluoro(phenyl)silicon(IV), respectively.

A liquid chromatography – tandem mass spectrometry method to measure a selected panel of uremic retention solutes derived from endogenous and colonic microbial metabolism

Chronic kidney disease (CKD) is associated with an increased risk of mortality and cardiovascular disease, which is, at least partly, mediated by the accumulation of so-called uremic retention solutes. Although there has been an increasing interest in the behavior of these solutes, derived from both the endogenous and colonic microbial metabolism, methods to simultaneously and accurately measure a broad panel of relevant uremic retention solutes remain scarce.We developed a highly sensitive ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method. A high throughput sample preparation was used with extraction of analytes from 50 μl serum using Ostro plate technology. For most solutes, stable isotopes labelled metabolites were used as internal standards. Chromatography was achieved using an Acquity UPLC CSH Fluoro Phenyl column. The total run time was 8 min, the mobile phase was a gradient of 0.1% formic acid in Milli-Q water and pure methanol at a flow rate of 0.5 ml min−1. Detection was performed using a tandem mass spectrometer with alternated positive and negative electrospray ionization.Calibration curves were linear for all solutes. Precision was assessed according to the NCCLS EP5-T guideline, being below 15% for all metabolites. Mean recoveries were between 83 and 104% for all metabolites. The validated method was successfully applied in a cohort of 488 patients with CKD.We developed and validated a sensitive and robust UPLC-MS/MS method for quantification of 15 uremic retention solutes derived from endogenous and colonic microbial metabolism. This method allows for studying the behavior and relevance of these solutes in patients with CKD.