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Strategies for Improving the Quantitative Bioanalytical Performance of LC-MS in Pharmacokinetic Studies

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Quantitative bioanalysis is urgently required for the evaluation of pharmacokinetic properties of a drug and to demonstrate the body exposure to the parent drug and/or metabolite for interpretation of the efficacy and toxicity. New trends in drug discovery and development will be always posing challenges on LC–MS-based quantitative bioanalysis. The focus of this minireview is to highlight the commonly used strategies for improving the quantitative bioanalytical performance including overcoming matrix effects and improving MS detectability. “LC-electrolyte effects” and “pulse gradient chromatography” proposed by our group are new approaches that have also showed potential efficiencies on improving overall bioassay performance, including lowering lower limit of quantification (LLOQ), enlarging upper limit of quantification (ULOQ), decreasing matrix effects, and overcoming elutropic effects, etc.. They should also work well in metabolic profiling studies and other important analytical fields, such as food pesticide residue analysis, environmental analysis, clinical and forensic toxicology, doping control, and so on.
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Keywords: LC-electrolyte effects; LC–MS; Pharmacokinetics; matrix effects; pulse gradient chromatography; sensitivity enhancement

Document Type: Research Article

Publication date: November 1, 2012

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  • Current Drug Metabolism aims to cover all the latest and outstanding developments in drug metabolism and disposition. The journal serves as an international forum for the publication of timely reviews in drug metabolism. Current Drug Metabolism is an essential journal for academic, clinical, government and pharmaceutical scientists who wish to be kept informed and up-to-date with the latest and most important developments. The journal covers the following areas:

    In vitro systems including CYP-450; enzyme induction and inhibition; drug-drug interactions and enzyme kinetics; pharmacokinetics, toxicokinetics, species scaling and extrapolations; P-glycoprotein and transport carriers; target organ toxicity and interindividual variability; drug metabolism and disposition studies; extrahepatic metabolism; phase I and phase II metabolism; recent developments for the identification of drug metabolites and adducts.
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