Browse
Submit Data
Databases
API
Help

Dataset Information

37 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Pharmacokinetic Assessment of Rottlerin from Mallotus philippensis Using a Highly Sensitive Liquid Chromatography-Tandem Mass Spectrometry-Based Bioanalytical Method.

ABSTRACT: Rottlerin is a key bioactive phytoconstituent present in the pericarp of Mallotus philippensis. It shows promising multifaceted pharmacological actions against cancer. However, there is hardly any report for the quantification of rottlerin in the biological matrix and on its pharmacokinetic behavior. Therefore, we aimed in the present study to assess selective in vitro ADME properties and in vivo pharmacokinetics of isolated and characterized rottlerin using a newly developed and validated liquid chromatography-tandem mass spectrometry-based highly sensitive bioanalytical method. The method was found to be simple (mobile phase and analytical column), sensitive (1.9 ng/mL), and rapid (run time of 2.5 min). All the validation parameters were within the acceptable criteria of the United States Food and Drug Administration's bioanalytical method validation guideline. The method was found to be very useful to assess lipophilicity, plasma stability, metabolic stability, plasma protein binding of rottlerin, as well as its oral and intravenous pharmacokinetics in mice. Rottlerin showed a number of drug-like pharmacokinetic properties (in vitro). Moreover, it displayed an excellent half-life (>2 h) and oral bioavailability (>35%) as compared to other members of natural phenolics. The present study is the first-time report of in vitro ADME properties and in vivo preclinical pharmacokinetics of rottlerin. The generated information is very much useful for its further development as a phytotherapeutics toward cancer therapy.

SUBMITTER: Manhas D

PROVIDER: S-EPMC8655892 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Correlating Mass Spectrometry Imaging and Liquid Chromatography-Tandem Mass Spectrometry for Tissue-Based Pharmacokinetic Studies.

Project description:Liquid chromatography-tandem mass spectrometry (LC-MS/MS) is a standard tool used for absolute quantification of drugs in pharmacokinetic (PK) studies. However, all spatial information is lost during the extraction and elucidation of a drugs biodistribution within the tissue is impossible. In the study presented here we used a sample embedding protocol optimized for mass spectrometry imaging (MSI) to prepare up to 15 rat intestine specimens at once. Desorption electrospray ionization (DESI) and matrix assisted laser desorption/ionization (MALDI) mass spectrometry imaging (MSI) were employed to determine the distributions and relative abundances of four benchmarking compounds in the intestinal segments. High resolution MALDI-MSI experiments performed at 10 µm spatial resolution allowed to determine the drug distribution in the different intestinal histological compartments to determine the absorbed and tissue bound fractions of the drugs. The low tissue bound drug fractions, which were determined to account for 56-66% of the total drug, highlight the importance to understand the spatial distribution of drugs within the histological compartments of a given tissue to rationalize concentration differences found in PK studies. The mean drug abundances of four benchmark compounds determined by MSI were correlated with the absolute drug concentrations. Linear regression resulted in coefficients of determination (R2) ranging from 0.532 to 0.926 for MALDI-MSI and R2 values ranging from 0.585 to 0.945 for DESI-MSI, validating a quantitative relation of the imaging data. The good correlation of the absolute tissue concentrations of the benchmark compounds and the MSI data provides a bases for relative quantification of compounds within and between tissues, without normalization to an isotopically labelled standard, provided that the compared tissues have inherently similar ion suppression effects.

| S-EPMC8954739 | biostudies-literature

Ocrelizumab quantitation by liquid chromatography-tandem mass spectrometry.

Project description:IntroductionOcrelizumab is a monoclonal anti-CD20 antibody approved for the treatment of multiple sclerosis (MS). The clinical value of therapeutic drug monitoring (TDM) for this antibody in treatment of MS is unknown, and an adequately specific and precise quantitation method for ocrelizumab in patient serum could facilitate investigation. Liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based quantitation methods have been shown to have higher analytic specificity and precision than enzyme-linked immunosorbent assays.ObjectivesTo establish and validate an LC-MS/MS-based quantitation method for ocrelizumab.MethodsWe present an LC-MS/MS-based quantitation method using immunocapture purification followed by trypsinization and analysis by a triple quadrupole mass analyzer obtaining results within the same day.ResultsWe found that the ocrelizumab peptide GLEWVGAIYPGNGDTSYNQK (Q1/Q3 Quantifier ion: 723.683+/590.77 y112+ Qualifier ion: 723.683+/672.30 y122+) can be used for quantitation and thereby developed a method for quantifying ocrelizumab in human serum with a quantitation range of 1.56 to 200 µg/mL. The method was validated in accordance with EMA requirements in terms of selectivity, carry-over, lower limit of quantitation, calibration curve, accuracy, precision and matrix effect. Ocrelizumab serum concentrations were measured in three MS patients treated with ocrelizumab, immediately before and after ocrelizumab infusion, with additional sampling after 2, 4, 8 and 12 weeks. Measured serum concentrations of ocrelizumab showed expected values for both Cmax and drug half-life over the sampled time period.ConclusionWe have established a reliable quantitation method for serum ocrelizumab that can be applied in clinical studies, facilitating the evaluation of ocrelizumab TDM in MS.

| S-EPMC9334332 | biostudies-literature

Liquid Chromatography-Tandem Mass Spectrometry Approach for Determining Glycosidic Linkages.

Project description:The structural analysis of carbohydrates remains challenging mainly due to the lack of rapid analytical methods able to determine and quantitate glycosidic linkages between the diverse monosaccharides found in natural oligosaccharides and polysaccharides. In this research, we present the first liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based method for the rapid and simultaneous relative quantitation of glycosidic linkages for oligosaccharide and polysaccharide characterization. The method developed employs ultrahigh-performance liquid chromatography coupled with triple quadrupole mass spectrometry (UHPLC/QqQ-MS) analysis performed in multiple reaction monitoring (MRM) mode. A library of 22 glycosidic linkages was built using commercial oligosaccharide standards. Permethylation and hydrolysis conditions along with LC-MS/MS parameters were optimized resulting in a workflow requiring only 50 ?g of substrate for the analysis. Samples were homogenized, permethylated, hydrolyzed, and then derivatized with 1-phenyl-3-methyl-5-pyrazolone (PMP) prior to analysis by UHPLC/MRM-MS. Separation by C18 reversed-phase UHPLC along with the simultaneous monitoring of derivatized terminal, linear, bisecting, and trisecting monosaccharide linkages by mass spectrometry is achieved within a 15 min run time. Reproducibility, efficacy, and robustness of the method was demonstrated with galactan ( Lupin) and polysaccharides within food such as whole carrots. The speed and specificity of the method enables its application toward the rapid glycosidic linkage analysis of oligosaccharides and polysaccharides.

| S-EPMC6221975 | biostudies-literature

Combined liquid chromatography-tandem mass spectrometry analysis of progesterone metabolites.

Project description:Progesterone has a number of important functions throughout the human body. While the roles of progesterone are well known, the possible actions and implications of progesterone metabolites in different tissues remain to be determined. There is a growing body of evidence that these metabolites are not inactive, but can have significant biological effects, as anesthetics, anxiolytics and anticonvulsants. Furthermore, they can facilitate synthesis of myelin components in the peripheral nervous system, have effects on human pregnancy and onset of labour, and have a neuroprotective role. For a better understanding of the functions of progesterone metabolites, improved analytical methods are essential. We have developed a combined liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for detection and quantification of progesterone and 16 progesterone metabolites that has femtomolar sensitivity and good reproducibility in a single chromatographic run. MS/MS analyses were performed in positive mode and under constant electrospray ionization conditions. To increase the sensitivity, all of the transitions were recorded using the Scheduled MRM algorithm. This LC-MS/MS method requires small sample volumes and minimal sample preparation, and there is no need for derivatization. Here, we show the application of this method for evaluation of progesterone metabolism in the HES endometrial cell line. In HES cells, the metabolism of progesterone proceeds mainly to (20S)-20-hydroxy-pregn-4-ene-3-one, (20S)-20-hydroxy-5?-pregnane-3-one and (20S)-5?-pregnane-3?,20-diol. The investigation of possible biological effects of these metabolites on the endometrium is currently undergoing.

| S-EPMC4332660 | biostudies-literature

Dried Blood Spot Technique-Based Liquid Chromatography-Tandem Mass Spectrometry Method as a Simple Alternative for Benznidazole Pharmacokinetic Assessment.

Project description:Chagas disease (CD) is recognized as one of the major neglected global tropical diseases. Benznidazole (BNZ) is the drug of choice for the treatment of adults, young infants, and newborns with CD. However, the pharmacokinetics (PK) of BNZ have been poorly evaluated in all age groups, with consequent gaps in knowledge about PK-pharmacodynamic relationships in CD. The purpose of this study was to develop and validate a bioanalytical method to quantify BNZ levels in small-volume whole-blood samples collected as dried blood spots (DBS). The analysis was performed using high-performance liquid chromatography-positive electrospray tandem mass spectrometry. PK evaluation in healthy male volunteers was conducted to verify the correlation between DBS and plasma BNZ concentrations. The calibration curve was linear from 50 to 20,000 ng · ml-1 Intra- and interday precision and bias values were less than 14.87% (n = 9) and 9.81% (n = 27), respectively. The recovery rates ranged from 94 to 100% with no matrix effect. There was no hematocrit level effect in a range of 20 to 70%. The PK results obtained from DBS and plasma were comparable (r2 = 0.8295) and equivalent to previously published information on BNZ. BNZ in DBS was stable at room temperature for more than one year. This article describes the first microsampling method for measuring BNZ levels in DBS that has the potential to facilitate broad implementation of PK in clinical trials involving adult and pediatric patients in remote areas and helps to address existing knowledge gaps in the treatment of CD.

| S-EPMC6256767 | biostudies-literature

Bioanalytical Method Development Using Liquid Chromatography with Amperometric Detection for the Pharmacokinetic Evaluation of Forsythiaside in Rats.

Project description:An analytical method entailing high-performance liquid chromatography coupled with electrochemical detection was developed for determining forsythiaside (FTS) in rat plasma. Rat plasma samples were prepared through efficient trichloroacetic acid deproteination. FTS and the internal standard were chromatographically separated on a reversed-phase core-shell silica C18 column (100 mm × 2.1 mm, i.d. 2.6 μm), with a mobile phase consisting of an acetonitrile-0.05-M phosphate solution (11.8:88.2, v/v), at a flow rate of 400 μL/min. The calibration curve, with r² > 0.999, was linear in the 20-1000 ng/mL range. The intra- and interday precision were less than 9.0%, and the accuracy ranged from 94.5% to 106.5% for FTS. The results indicated that the newly developed HPLC-EC method is more sensitive than previous reported methods using UV detection, and this new analytical method is applied successfully for the pharmacokinetic study of FTS. The hydrogel delivery system can efficiently improve bioavailability and mean residual time for FTS, as evidenced by the 2.5- and 6.3-fold increase of the area under the curve and the extension of the half-life, respectively.

| S-EPMC6274433 | biostudies-literature

Pharmacokinetic study of the main components of Tanreqing capsules and Tanreqing injections in beagles by liquid chromatography-tandem mass spectrometry.

Project description:BackgroundTanreqing capsules (TRQCs) and Tanreqing injections (TRQIs) are widely used in the treatment of respiratory diseases. In this study, a simple, rapid, and sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed for simultaneous quantification of the main components of Tanreqing, which include chlorogenic acid, ursodeoxycholic acid, chenodeoxycholic acid, and baicalin, in beagle dog plasma to compare their pharmacokinetic parameters.MethodsPlasma samples were pretreated with protein precipitation. Chromatographic separation was performed on Waters Acquity UPLC HSS T3 (2.1 mm × 100 mm, 1.8 μm) column using a gradient elution with (A) 0.1% (v/v) formic acid aqueous solution and (B) acetonitrile. Six healthy beagles were divided into two groups, and a crossover, comparative pharmacokinetic study of TRQC (0.09 g/kg) and TRQI (0.5 mL/kg) after a single-dose administration or daily doses over 7 days was carried out. One group was administrated a single dose of TRQC and followed continuously for 7 days, whereas the other group was treated with TRQI in the same way.ResultsThe calibration curves were linear over the ranges of 2.00-1000.00 ng/mL for baicalin, 10.00-5000.00 ng/mL for ursodeoxycholic acid, 1.00-500.00 ng/mLfor chenodeoxycholic acid and chlorogenic acid, respectively. The relative standard deviation of both intra-day and inter-day accuracy is less than 11.23%. The average extraction recovery of all compounds was greater than 82.21%. The major pharmacokinetic parameters of the four compounds were not significantly different between the two formulations (P > 0.05).ConclusionsThe measured levels of the four major components of TRQCs and TRQIs were comparable in these dogs, providing a reference for the clinical application of TRQCs instead of TRQIs.

| S-EPMC9721025 | biostudies-literature

Quantification of regional DNA methylation by liquid chromatography/tandem mass spectrometry.

Project description:Promoter hypermethylation-associated tumor suppressor gene (TSG) silencing has been explored as a therapeutic target for hypomethylating agents. Promoter methylation change may serve as a pharmacodynamic endpoint for evaluation of the efficacy of these agents and predict the patient's clinical response. Here a liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay has been developed for quantitative regional DNA methylation analysis using the molar ratio of 5-methyl-2'-deoxycytidine (5mdC) to 2'-deoxycytidine (2dC) in the enzymatic hydrolysate of fully methylated bisulfite-converted polymerase chain reaction (PCR) amplicons as the methylation indicator. The assay can differentiate 5% of promoter methylation level with an intraday precision ranging from 3 to 16% using two TSGs: HIN-1 and RASSF1A. This method was applied to characterize decitabine-induced promoter DNA methylation changes of these two TSGs in a breast cancer MCF-7 cell line. Promoter methylation of these TSGs was found to decrease in a dose-dependent manner. Correspondingly, the expression of these TSGs was enhanced. The sensitivity and reproducibility of the method make it a valuable tool for specific gene methylation analysis that could aid characterization of hypomethylating activity on specific genes by hypomethylating agents in a clinical setting.

| S-EPMC3939067 | biostudies-literature

Proteomic analysis of endodontic infections by liquid chromatography-tandem mass spectrometry.

Project description:IntroductionEndodontic infections are very prevalent and have a polymicrobial etiology characterized by complex interrelationships between endodontic microorganisms and the host defenses. Proteomic analysis of endodontic infections can provide global insights into the invasion, pathogenicity mechanisms, and multifactorial interactions existing between root canal bacteria and the host in the initiation and progression of apical periodontitis. The purpose of this study was to apply proteomic techniques such as liquid chromatography-tandem mass spectrometry (LC-MS/MS) for the identification of proteins of bacterial origin present in endodontic infections.MethodsEndodontic specimens were aseptically obtained from seven patients with root canal infections. Protein mixtures were subjected to tryptic in-solution digestion and analysed by reverse-phase nano-LC-MS/MS followed by a database search.ResultsProteins, mainly of cell wall or membrane origin, from endodontic bacteria especially Enterococcus faecalis, Enterococcus faecium, Porphyromonas gingivalis, Fusobacterium nucleatum, and Treponema denticola were identified from all the samples tested. Identified proteins included adhesins, autolysins, proteases, virulence factors, and antibiotic-resistance proteins.ConclusionsLC-MS/MS offers a sensitive analytical platform to study the disease processes in the root canal environment. The array of proteins expressed in endodontic infections reflects the complex microbial presence and highlights the bacterial species involved in the inflammatory process.

| S-EPMC2744886 | biostudies-literature

Liquid Chromatography Tandem Mass Spectrometry Quantification of 13C-Labeling in Sugars.

Project description:Subcellular compartmentation has been challenging in plant 13C-metabolic flux analysis. Indeed, plant cells are highly compartmented: they contain vacuoles and plastids in addition to the regular organelles found in other eukaryotes. The distinction of reactions between compartments is possible when metabolites are synthesized in a particular compartment or by a unique pathway. Sucrose is an example of such a metabolite: it is specifically produced in the cytosol from glucose 6-phosphate (G6P) and fructose 6-phosphate (F6P). Therefore, determining the 13C-labeling in the fructosyl and glucosyl moieties of sucrose directly informs about the labeling of cytosolic F6P and G6P, respectively. To date, the most commonly used method to monitor sucrose labeling is by nuclear magnetic resonance, which requires substantial amounts of biological sample. This study describes a new methodology that accurately measures the labeling in free sugars using liquid chromatography tandem mass spectrometry (LC-MS/MS). For this purpose, maize embryos were pulsed with [U-13C]-fructose, intracellular sugars were extracted, and their time-course labeling was analyzed by LC-MS/MS. Additionally, extracts were enzymatically treated with hexokinase to remove the soluble hexoses, and then invertase to cleave sucrose into fructose and glucose. Finally, the labeling in the glucosyl and fructosyl moieties of sucrose was determined by LC-MS/MS.

| S-EPMC7022953 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data