BibSonomy publications for /user/kanefendt/StabilityFri Feb 05 11:28:39 CET 2010AAPS.J.2E117-E122Best practices during bioanalytical method validation for the characterization of assay reagents and the evaluation of analyte stability in assay standards, quality controls, and study samples92007Animals Binding Biopharmaceutics Chemistry Control Drug Humans Pharmaceutical Pharmacokinetics Preparations Quality Reference Reproducibility Results Solutions Stability Standards analysis deficiency metabolism methods of standards Characterization of the stability of analytes in biological samples collected during clinical studies together with that of critical assay reagents, including analyte stock solutions, is recognized as an important component of bioanalytical assay validation. Deficiencies in these areas often come to light during regulatory inspections. Best practices, based on current regulatory guidance, for the assessment of these issues as they pertain to ligand binding and chromatographic assays are covered in this review. Additionally, consensus recommendations reached during the recent AAPS/FDA Workshop on bioanalytical assay validation are highlightedFri Feb 05 11:28:39 CET 2010Pharm.Res.101962-1973Quantitative bioanalytical methods validation and implementation: best practices for chromatographic and ligand binding assays242007& Administration Animals Artifacts Assay Binding Biological Body Calibration Chemistry Chromatography Control Documentation Drug Fluids Food Government Guidelines Humans Macromolecular Pharmaceutical Quality Radioligand Reference Regulation Reproducibility Research Results Species Specificity Stability Standards States Substances Technology Topic United and as jurisprudence legislation methods of standards The Third AAPS/FDA Bioanalytical Workshop, entitled "Quantitative Bioanalytical Methods Validation and Implementation: Best Practices for Chromatographic and Ligand Binding Assays" was held on May 1-3, 2006 in Arlington, VA. The format of this workshop consisted of presentations on bioanalytical topics, followed by discussion sessions where these topics could be debated, with the goal of reaching consensus, or identifying subjects where addition input or clarification was required. The discussion also addressed bioanalytical validation requirements of regulatory agencies, with the purpose of clarifying expectations for regulatory submissions. The proceedings from each day were reviewed and summarized in the evening sessions among the speakers and moderators of the day. The consensus summary was presented back to the workshop on the last day and was further debated. This communication represents the distillate of the workshop proceedings and provides the summary of consensus reached andFri Feb 05 11:28:39 CET 2010Nat.Genet.2153-159Missense mutations interfere with VEGFR-3 signalling in primary lymphoedema2520005 Activation Alleles Animals C Cell Chemistry Chromosomes Data Dominant Endothelial Enzyme Factor Factors Female Fusion Genes Growth Half-Life Human Humans Infant Kinase Kinases Laboratories Line Lymphedema Male Mice Missense Models Molecular Mutation Newborn Pair Pedigree Phosphorylation Protein Protein-Tyrosine Proteins Receptor Receptor-3 Receptors Recombinant Research Sequence Signal Stability Structure Surface Transcriptional Transduction Tyrosine Vascular congenital drug effects genetics metabolism pharmacology protein secondary Primary lymphoedema is a rare, autosomal dominant disorder that leads to a disabling and disfiguring swelling of the extremities and, when untreated, tends to worsen with time. Here we link primary human lymphoedema to the FLT4 locus, encoding vascular endothelial growth factor receptor-3 (VEGFR-3), in several families. All disease-associated alleles analysed had missense mutations and encoded proteins with an inactive tyrosine kinase, preventing downstream gene activation. Our study establishes that VEGFR-3 is important for normal lymphatic vascular function and that mutations interfering with VEGFR-3 signal transduction are a cause of primary lymphoedemaFri Feb 05 11:28:39 CET 2010J.Pharm.Biomed.Anal.8-12629-637Method validation in the bioanalytical laboratory81990Chemistry Drug Freezing Mass Pharmaceutical Reference Research Solubility Species Specificity Spectrometry Stability Standards Temperature instrumentation methods standards Bioanalytical methods, based on a variety of physico-chemical and biological techniques such as chromatography, immunoassay and mass spectrometry, must be validated prior to and during use to engender confidence in the results generated. The fundamental criteria for assessing the reliability and overall performance of a bioanalytical method are: the evaluation of drug and analyte stability, selectivity, limits of quantification and detection, accuracy, precision, linearity and recovery. The extent to which a method is validated is dependent on its prospective use, the number of samples to be assayed and the use to which the data are put. Specific analytical techniques may require additional validation such as antibody-binding characteristics, peak purity determination, evaluation of matrix effects or structural confirmation of the analyte. Ideally each assay should be cross-validated with a method utilizing a highly specific detector such as a mass spectrometer. Once in use, the perfor