FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2245373153> ?p ?o ?g. }

• W2245373153 abstract "Poor pharmacokinetics is one of the reasons for the withdrawal of drug candidates from clinical trials. There is an urgent need for investigating in vitro ADME (absorption, distribution, metabolism and excretion) properties and recognising unsuitable drug candidates as early as possible in the drug development process. Current throughput of in vitro ADME profiling is insufficient because effective new synthesis techniques, such as drug design in silico and combinatorial synthesis, have vastly increased the number of drug candidates. Assay technologies for larger sets of compounds than are currently feasible are critically needed. The first part of this work focused on the evaluation of cocktail strategy in studies of drug permeability and metabolic stability. N-in-one liquid chromatography-tandem mass spectrometry (LC/MS/MS) methods were developed and validated for the multiple component analysis of samples in cocktail experiments. Together, cocktail dosing and LC/MS/MS were found to form an effective tool for increasing throughput. First, cocktail dosing, i.e. the use of a mixture of many test compounds, was applied in permeability experiments with Caco-2 cell culture, which is a widely used in vitro model for small intestinal absorption. A cocktail of 7-10 reference compounds was successfully evaluated for standardization and routine testing of the performance of Caco-2 cell cultures. Secondly, cocktail strategy was used in metabolic stability studies of drugs with UGT isoenzymes, which are one of the most important phase II drug metabolizing enzymes. The study confirmed that the determination of intrinsic clearance (Clint) as a cocktail of seven substrates is possible. The LC/MS/MS methods that were developed were fast and reliable for the quantitative analysis of a heterogenous set of drugs from Caco-2 permeability experiments and the set of glucuronides from in vitro stability experiments. The performance of a new ionization technique, atmospheric pressure photoionization (APPI), was evaluated through comparison with electrospray ionization (ESI), where both techniques were used for the analysis of Caco-2 samples. Like ESI, also APPI proved to be a reliable technique for the analysis of Caco-2 samples and even more flexible than ESI because of the wider dynamic linear range. The second part of the experimental study focused on metabolite profiling. Different mass spectrometric instruments and commercially available software tools were investigated for profiling metabolites in urine and hepatocyte samples. All the instruments tested (triple quadrupole, quadrupole time-of-flight, ion trap) exhibited some good and some bad features in searching for and identifying of expected and non-expected metabolites. Although, current profiling software is helpful, it is still insufficient. Thus a time-consuming largely manual approach is still required for metabolite profiling from complex biological matrices." @default.
• W2245373153 created "2016-06-24" @default.
• W2245373153 creator A5030928998 @default.
• W2245373153 date "2008-01-25" @default.
• W2245373153 modified "2023-09-27" @default.
• W2245373153 title "Liquid Chromatography-Mass Spectrometry in Studies of Drug Metabolism and Permeability" @default.
• W2245373153 cites W1592112313 @default.
• W2245373153 cites W1645044045 @default.
• W2245373153 cites W2062921804 @default.
• W2245373153 cites W571906781 @default.
• W2245373153 cites W624149752 @default.
• W2245373153 hasPublicationYear "2008" @default.
• W2245373153 type Work @default.
• W2245373153 sameAs 2245373153 @default.
• W2245373153 citedByCount "0" @default.
• W2245373153 crossrefType "journal-article" @default.
• W2245373153 hasAuthorship W2245373153A5030928998 @default.
• W2245373153 hasConcept C104317684 @default.
• W2245373153 hasConcept C112705442 @default.
• W2245373153 hasConcept C162356407 @default.
• W2245373153 hasConcept C185592680 @default.
• W2245373153 hasConcept C2775905019 @default.
• W2245373153 hasConcept C2780035454 @default.
• W2245373153 hasConcept C2994297994 @default.
• W2245373153 hasConcept C43617362 @default.
• W2245373153 hasConcept C55493867 @default.
• W2245373153 hasConcept C64489805 @default.
• W2245373153 hasConcept C69366308 @default.
• W2245373153 hasConcept C71924100 @default.
• W2245373153 hasConcept C89311334 @default.
• W2245373153 hasConcept C98274493 @default.
• W2245373153 hasConceptScore W2245373153C104317684 @default.
• W2245373153 hasConceptScore W2245373153C112705442 @default.
• W2245373153 hasConceptScore W2245373153C162356407 @default.
• W2245373153 hasConceptScore W2245373153C185592680 @default.
• W2245373153 hasConceptScore W2245373153C2775905019 @default.
• W2245373153 hasConceptScore W2245373153C2780035454 @default.
• W2245373153 hasConceptScore W2245373153C2994297994 @default.
• W2245373153 hasConceptScore W2245373153C43617362 @default.
• W2245373153 hasConceptScore W2245373153C55493867 @default.
• W2245373153 hasConceptScore W2245373153C64489805 @default.
• W2245373153 hasConceptScore W2245373153C69366308 @default.
• W2245373153 hasConceptScore W2245373153C71924100 @default.
• W2245373153 hasConceptScore W2245373153C89311334 @default.
• W2245373153 hasConceptScore W2245373153C98274493 @default.
• W2245373153 hasLocation W22453731531 @default.
• W2245373153 hasOpenAccess W2245373153 @default.
• W2245373153 hasPrimaryLocation W22453731531 @default.
• W2245373153 hasRelatedWork W1621363655 @default.
• W2245373153 hasRelatedWork W1968507060 @default.
• W2245373153 hasRelatedWork W2089538251 @default.
• W2245373153 hasRelatedWork W2116184147 @default.
• W2245373153 hasRelatedWork W2257222609 @default.
• W2245373153 hasRelatedWork W2560199866 @default.
• W2245373153 hasRelatedWork W2584405581 @default.
• W2245373153 hasRelatedWork W2592985166 @default.
• W2245373153 hasRelatedWork W2594355653 @default.
• W2245373153 hasRelatedWork W2779897130 @default.
• W2245373153 hasRelatedWork W2800776036 @default.
• W2245373153 hasRelatedWork W2902337678 @default.
• W2245373153 hasRelatedWork W2903341012 @default.
• W2245373153 hasRelatedWork W29256430 @default.
• W2245373153 hasRelatedWork W3017099625 @default.
• W2245373153 hasRelatedWork W3018540053 @default.
• W2245373153 hasRelatedWork W3034508405 @default.
• W2245373153 hasRelatedWork W3128963160 @default.
• W2245373153 hasRelatedWork W26605232 @default.
• W2245373153 hasRelatedWork W2842807489 @default.
• W2245373153 isParatext "false" @default.
• W2245373153 isRetracted "false" @default.
• W2245373153 magId "2245373153" @default.
• W2245373153 workType "article" @default.