Swiss BioQuant AG

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Swiss BioQuant AG

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Bridel C.,VU University Amsterdam | Hoffmann T.,Probiodrug | Meyer A.,Probiodrug | Durieux S.,VU University Amsterdam | And 5 more authors.
Alzheimer's Research and Therapy | Year: 2017

Background: Pyroglutamylation of truncated Aβ peptides, which is catalysed by enzyme glutaminyl cyclase (QC), generates pE-Aβ species with enhanced aggregation propensities and resistance to most amino-peptidases and endo-peptidases. pE-Aβ species have been identified as major constituents of Aβ plaques and reduction of pE-Aβ species is associated with improvement of cognitive tasks in animal models of Alzheimer’s disease (AD). Pharmacological inhibition of QC has thus emerged as a promising therapeutic approach for AD. Here, we question whether cerebrospinal fluid (CSF) QC enzymatic activity differs between AD patients and controls and whether inflammatory or angiogenesis mediators, some of which are potential QC substrates, and/or Aβ peptides may serve as pharmacodynamic read-outs for QC inhibition. Methods: QC activity, Aβ peptides and inflammatory or angiogenesis mediators were measured in CSF of a clinically well-characterized cohort of 20 mild AD patients, 20 moderate AD patients and 20 subjective memory complaints (SMC) controls. Correlation of these parameters with core diagnostic CSF AD biomarkers (Aβ42, tau and p-tau) and clinical features was evaluated. Results: QC activity shows a tendency to decrease with AD progression (p = 0.129). The addition of QC activity to biomarkers tau and p-tau significantly increases diagnostic power (ROC-AUCTAU = 0.878, ROC-AUCTAU&QC = 0.939 and ROC-AUCpTAU = 0.820, ROC-AUCpTAU&QC = 0.948). In AD and controls, QC activity correlates with Aβ38 (r = 0.83, p < 0.0001) and Aβ40 (r = 0.84, p < 0.0001), angiogenesis mediators (Flt1, Tie2, VEGFD, VCAM-1 and ICAM-1, r > 0.5, p < 0.0001) and core diagnostic biomarkers (r > 0.35, p = <0.0057). QC activity does not correlate with MMSE or ApoE genotype. Conclusions: Aβ38, Aβ40 and angiogenesis mediators (Flt1, Tie2, VEGFD, VCAM-1 and ICAM-1) are potential pharmacodynamic markers of QC inhibition, because their levels closely correlate with QC activity in AD patients. The addition of QC activity to core diagnostic CSF biomarkers may be of specific interest in clinical cases with discordant imaging and biochemical biomarker results. © 2017 The Author(s).


Blume H.,SocraTec CSC GmbH | Blume H.,SocraTec RandD GmbH | Brendel E.,Bayer AG | Brudny-Kloppel M.,Bayer AG | And 4 more authors.
European Journal of Pharmaceutical Sciences | Year: 2011

This is a summary report of the workshop on the EMA Draft Guideline on Validation of Bioanalytical Methods held April 15-16th 2010 in Brussels (Belgium) and jointly organised by the European Bioanalysis Forum (EBF) and the European Federation for Pharmaceutical Sciences (EUFEPS). Aim of the workshop was to discuss the current scientific knowledge in the area of bioanalysis, the regulatory requirements with special focus on the new Draft Guideline and their subsequent implementation to the work in bioanalytical laboratories. Comments on the Draft Guideline were presented and discussed with representatives from regulatory authorities in Europe. The workshop started with discussions on the scope of the Guideline and the need for implementation of GLP. A special focus was set on method validation of chromatographic procedures and subsequent study sample analysis. In addition, requirements for ligand-binding assays were briefly addressed. Intention of this Conference Report is to summarise important aspects of the discussions in order to draw certain conclusions, and to identify points which remain open and may require clarification at a later stage. © 2011 Elsevier B.V.


Sangster T.,Charles River Associates | Maltas J.,BASi | Struwe P.,Celerion | Hillier J.,Gen-Probe | And 27 more authors.
Bioanalysis | Year: 2012

The 5th Global CRO Council for Bioanalysis (GCC) meeting, held in Barcelona, Spain, in November 2011, provided a unique opportunity for CRO leaders to openly share opinions, perspectives and to agree on bioanalytical recommendations on incurred sample reproducibility in multi-analyte assays, regulation of quality assurance/bioanalytical consultants and regulatory requirements for GCP. © 2012 Future Science Ltd.


Lowes S.,Quintiles | Boterman M.,ABL | Doig M.,ABS Laboratories | Breda M.,Accelera | And 88 more authors.
Bioanalysis | Year: 2012

An open letter written by the Global CRO Council for Bioanalysis (GCC) describing the GCC survey results on stability data from co-administered and co-formulated drugs was sent to multiple regulatory authorities on 14 December 2011. This letter and further discussions at different GCC meetings led to subsequent recommendations on this topic of widespread interest within the bioanalytical community over the past 2 years. © 2012 Future Science Ltd.


Grant
Agency: European Commission | Branch: FP7 | Program: BSG-SME | Phase: SME-1 | Award Amount: 1.42M | Year: 2009

The project will focus on the pre-clinical development of carbon monoxide releasing molecules (CORMs) for the treatment of rheumatoid arthritis (RA). Carbon monoxide (CO) has been shown, by several renowned laboratories around the world, to have a number of anti-inflammatory properties which turn it into an exceptionally promising compound against chronic inflammatory diseases such as RA. In its gaseous form CO will hardly be applicable as a drug in a clinical setting. One proponent SME, has conceived and produced a large number of molecules which will release or donate CO, inside the organism, in specific physiological or pathological conditions. These molecules, called CORMs, hold the promise of delivering CO in controlled amounts, at specific rates and in a targeted manner to inflamed tissues such as arthritic joints. In recent months some of these CORMs have been tested in preliminary experiments using rodent models of RA, and have yielded encouraging results in terms of efficacy and toxicity. The main goal of this project will be: to select a small number of exceptionally promising CORMs for the treatment of RA, to develop the best formulations for those compounds, to test their detailed pharmacological and toxicological properties, and ultimately arrive at one lead candidate for clinical development. With this aim, three different SMEs will join their resources, critical mass and knowledge in the field of CORMs, pharmacological test, analysis and standardization and validation of developed assays to gain the ambitious, but reasonable goal: at least one new molecule in clinical trials.


Ingelse B.,Merck And Co. | Ingelse B.,Quintiles | Barroso B.,Astellas Pharma Europe | Gray N.,Covance | And 6 more authors.
Bioanalysis | Year: 2014

Recent guidelines on bioanalytical method validation have recommended to investigate matrix effects in special matrices such as hemolytic and hyperlipidemic plasma. However, these guidelines were not clear on how to implement these recommendations. The European Bioanalysis Forum has discussed this topic in depth and has asked for feedback from member companies. Those discussions have resulted in more specific guidance on how to define hemolytic and hyperlipidemic plasma, how to validate bioanalytical methods for these matrices and how to deal with hemolytic and hyperlipidemic study samples. These recommendations are presented in this manuscript. © 2014 Future Science Ltd.


Enzler M.,Swiss BioQuant AG | Schipp S.,Swiss BioQuant AG | Nicolas L.B.,Actelion Pharmaceuticals | Dingemanse J.,Actelion Pharmaceuticals | Siethoff C.,Swiss BioQuant AG
Journal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences | Year: 2012

An HPLC-MS/MS method was developed and validated for the quantification of 6-keto prostaglandin F1α, the stable hydrolysis product of prostacyclin, and its metabolites 2,3-dinor-6-keto prostaglandin F1α and 6,15-diketo-13,14-dihydro prostaglandin F1α in human plasma. For sample preparation, a solid phase extraction step was combined with a column switching approach for analytes enrichment and further sample clean-up of the processed sample. The assay was validated in the concentration range 50.0-5000. pg/mL for 6-keto prostaglandin F1α and 6,15-diketo-13,14-dihydro prostaglandin F1α, and 100-10,000. pg/mL for 2,3-dinor-6-keto prostaglandin F1α. The inter-batch precision was better than 12.7%, 9.2%, and 9.4% for 6-keto prostaglandin F1α, 2,3-dinor-6-keto prostaglandin F1α, and 6,15-diketo-13,14-dihydro prostaglandin F1α, respectively. The inter-batch accuracy was between 97.3% and 100.8% for 6-keto prostaglandin F1α, between 97.5% and 103.0% for 2,3-dinor-6-keto prostaglandin F1α, and between 92.0% and 100.0% for 6,15-diketo-13,14-dihydro prostaglandin F1α. Further it has been demonstrated that the analytes were stable in plasma for 20. h at room temperature, during three freeze-and-thaw cycles, for 96 days at -25°C storage temperature, and 50. h in the autosampler tray at room temperature. © 2012 Elsevier B.V.


PubMed | Swiss BioQuant AG
Type: | Journal: Journal of chromatography. B, Analytical technologies in the biomedical and life sciences | Year: 2012

An HPLC-MS/MS method was developed and validated for the quantification of 6-keto prostaglandin F1, the stable hydrolysis product of prostacyclin, and its metabolites 2,3-dinor-6-keto prostaglandin F1 and 6,15-diketo-13,14-dihydro prostaglandin F1 in human plasma. For sample preparation, a solid phase extraction step was combined with a column switching approach for analytes enrichment and further sample clean-up of the processed sample. The assay was validated in the concentration range 50.0-5000 pg/mL for 6-keto prostaglandin F1 and 6,15-diketo-13,14-dihydro prostaglandin F1, and 100-10,000 pg/mL for 2,3-dinor-6-keto prostaglandin F1. The inter-batch precision was better than 12.7%, 9.2%, and 9.4% for 6-keto prostaglandin F1, 2,3-dinor-6-keto prostaglandin F1, and 6,15-diketo-13,14-dihydro prostaglandin F1, respectively. The inter-batch accuracy was between 97.3% and 100.8% for 6-keto prostaglandin F1, between 97.5% and 103.0% for 2,3-dinor-6-keto prostaglandin F1, and between 92.0% and 100.0% for 6,15-diketo-13,14-dihydro prostaglandin F1. Further it has been demonstrated that the analytes were stable in plasma for 20 h at room temperature, during three freeze-and-thaw cycles, for 96 days at -25 C storage temperature, and 50h in the autosampler tray at room temperature.

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