Bioanalytical Laboratory

Assen, Netherlands

Bioanalytical Laboratory

Assen, Netherlands
Time filter
Source Type

News Article | May 9, 2017

LEXINGTON, Mass.--(BUSINESS WIRE)--Quanterix Corporation, a company digitizing biomarker analysis to advance the science of precision health, today announced that Smithers Avanza, a contract research organization supporting the pharmaceutical industry, is adding the Simoa HD-1 Analyzer to its Bioanalytical Laboratory. With this addition, Smithers Avanza will provide its customers with an opportunity to leverage Simoa’s unprecedented levels of sensitivity and automation capabilities in drug discovery and development. Smithers Avanza chose the Simoa HD-1 instrument from Quanterix to complement the other instruments in the bioanalytical laboratory, allowing the company to increase testing volume and utilize the automation features to increase efficiency. Simoa enables development of methods to provide much earlier disease detection, better prognoses and enhanced treatment methods to improve the quality of life and longevity of the population for generations to come. “Simoa is changing the way in which the biology of health and disease is studied by giving organizations, like Smithers Avanza, the ability to closely examine critical biomarkers to improve the probabilities of clinical trial success by over 200 percent,” said Kevin Hrusovsky, CEO and Executive Chairman, Quanterix. “By providing accessibility to our Simoa technology, we look forward to advancements and new discoveries in both pre-clinical and clinical research that will be uncovered by Smithers Avanza customers in the future.” “We are continuously looking at how we can provide greater value to our clients,” said Ira DuBey, Executive Vice President, Smithers Avanza Bioanalytical Services. “Adding technology such as the Simoa HD-1 that analyzes biologics and biomarkers with a very high degree of sensitivity helps us to deliver the testing results our clients are looking for.” Smithers Avanza is a contract research organization (CRO) supporting the pharmaceutical industry. Our scientists have expertise in large molecule bioanalysis, assay development, validation and sample analysis at our GLP- and GCP-compliant and CLIA-certified laboratory. Quanterix is a company that’s digitizing biomarker analysis to advance the science of precision health. The company’s digital health solution, Simoa, is changing the way in which healthcare is provided today by giving researchers the ability to closely examine the continuum from health to disease. In doing so, Quanterix enables much earlier disease detection, better prognoses and enhanced treatment methods to improve the quality of life and longevity of the population for generations to come. The technology is currently being used for applications in a majority of therapeutic areas, including oncology, neurology, cardiology, inflammation and infectious disease. The company was established in 2007 and is located in Lexington, Massachusetts.

Bronsema K.J.,Bioanalytical Laboratory | Bronsema K.J.,University of Groningen | Bischoff R.,University of Groningen | Bouche M.-P.,Ablynx | And 3 more authors.
Bioanalysis | Year: 2015

Background: A major challenge in protein quantitation based on enzymatic digestion of complex biological samples and subsequent LC-MS/MS analysis of a signature peptide is dealing with the high complexity of the matrix after digestion, which can reduce sensitivity considerably. Results: Using single cartridge multidimensional SPE, sufficient selectivity was introduced to allow quantitation in 50 l of plasma down to 10.0 ng/ml (0.3 nM). An inhouse prepared 18O-labeled signature peptide was used as the internal standard. The procedure was validated for human and rabbit plasma. Conclusion: The developed SPE procedure allowed the sensitive and selective LC-MS/MS quantitation of the Nanobody® without the use of antibodies. When appropriate precautions are taken, the 18O-labeled peptide is a practical and economical alternative to custom synthesis. © 2015 Future Science Ltd.

Ongay S.,University of Groningen | Hendriks G.,Bioanalytical Laboratory | Hermans J.,University of Groningen | van den Berge M.,University of Groningen | And 4 more authors.
Journal of Chromatography A | Year: 2014

In spite of the data suggesting the potential of urinary desmosine (DES) and isodesmosine (IDS) as biomarkers for elevated lung elastic fiber turnover, further validation in large-scale studies of COPD populations, as well as the analysis of longitudinal samples is required. Validated analytical methods that allow the accurate and precise quantification of DES and IDS in human urine are mandatory in order to properly evaluate the outcome of such clinical studies. In this work, we present the development and full validation of two methods that allow DES and IDS measurement in human urine, one for the free and one for the total (free. +. peptide-bound) forms. To this end we compared the two principle approaches that are used for the absolute quantification of endogenous compounds in biological samples, analysis against calibrators containing authentic analyte in surrogate matrix or containing surrogate analyte in authentic matrix. The validated methods were employed for the analysis of a small set of samples including healthy never-smokers, healthy current-smokers and COPD patients. This is the first time that the analysis of urinary free DES, free IDS, total DES, and total IDS has been fully validated and that the surrogate analyte approach has been evaluated for their quantification in biological samples. Results indicate that the presented methods have the necessary quality and level of validation to assess the potential of urinary DES and IDS levels as biomarkers for the progression of COPD and the effect of therapeutic interventions. © 2014 Elsevier B.V.

Van De Merbel N.C.,Bioanalytical Laboratory | Van De Merbel N.C.,University of Groningen | De Vries R.,Janssen RandD
Bioanalysis | Year: 2013

Apart from the well-known matrix effects that can occur in ESI LC-MS, biological matrices may have other effects influencing the quantitative reliability of bioanalytical methods. In this paper, six case studies are presented that show the effect that aging, that is the change in properties and composition of biological matrices over time, can have on the performance of bioanalytical methods. It is shown that selectivity can be affected due to the formation or disappearance of endogenous compounds. Stability can be influenced because of the decrease (or increase) of enzyme activities and recovery can be impacted if the extractability from binding sites in the matrix is enhanced or decreased. A general discussion on the importance of these matrix effects is provided as well as a perspective on how to properly address them in the method-development and validation stages of regulated bioanalysis. © 2013 Future Science Ltd.

Van De Merbel N.,Bioanalytical Laboratory | Savoie N.,Algorithme Pharma Inc. | Yadav M.,Alkem Laboratories | Ohtsu Y.,Astellas Pharma Inc. | And 5 more authors.
AAPS Journal | Year: 2014

This paper provides a comprehensive overview of stability-related aspects of quantitative bioanalysis and recommends science-based best practices, covering small and large molecules as well as chromatographic and ligand-binding assays. It addresses general aspects, such as the use of reference values, transferability and treatment of failing stability results, and also focuses on specific types of stability assessment: bench-top, freeze/thaw and long-term frozen stability, stock stability, extract stability, stability in whole blood, tissue and urine, and stability of endogenous analytes, in special matrix types and in incurred samples. © 2014 American Association of Pharmaceutical Scientists.

Bronsema K.J.,University of Groningen | Bronsema K.J.,Bioanalytical Laboratory | Bischoff R.,University of Groningen | Van De Merbel N.C.,University of Groningen | Van De Merbel N.C.,Bioanalytical Laboratory
Analytical Chemistry | Year: 2013

Two important aspects of peptide and protein quantification by LC-MS/MS, the enzymatic digestion step and the internal standardization approach, were systematically investigated with a small protein, salmon calcitonin, which could be analyzed both without and with digestion. Quantification of undigested salmon calcitonin, after solid-phase extraction from plasma, resulted in a lower limit of quantification of 10 pg/mL, while introduction of a tryptic digestion step, followed by quantification of a signature peptide, increased this to 50 pg/mL. The sensitivity was reduced by interferences in the selected reaction monitoring (SRM) transition of the signature peptide due to the increase in sample complexity caused by the digestion and a less selective SRM transition of the signature peptide as compared to undigested salmon calcitonin. Eight internal standardization approaches were compared with respect to accuracy and precision in workflows with and without digestion. Analogue and stable-isotope-labeled (SIL) internal standards were evaluated including an in-house created 18O-labeled peptide, a cleavable SIL peptide, and an internal standard created by differential derivatization of the signature peptide. We conclude that the best internal standard for the workflows both with and without digestion was the SIL form of the analyte, although the use of several SIL signature peptides and a differentially derivatized signature peptide also resulted in methods with performances which meet the FDA guidelines. © 2013 American Chemical Society.

Wilffert D.,University of Groningen | Reis C.R.,University of Groningen | Reis C.R.,Southwestern Medical Center | Hermans J.,University of Groningen | And 7 more authors.
Analytical Chemistry | Year: 2013

The major challenge in targeted protein quantification by LC-MS/MS in serum lies in the complexity of the biological matrix with regard to the wide diversity of proteins and their extremely large dynamic concentration range. In this study, an LC-MS/MS method was developed for the simultaneous quantification of the 60-kDa biopharmaceutical proteins recombinant human tumor necrosis factor-related apoptosis-inducing ligand wild type (rhTRAILWT) and its death receptor 4 (DR4)-specific variant rhTRAIL4C7 in human and mouse serum. Selective enrichment of TRAIL was accomplished by immobilized metal affinity chromatography (IMAC), which was followed by tryptic digestion of the enriched sample and quantification of a suitable signature peptide. For absolute quantification, 15N-metabolically labeled internal standards of rhTRAILWT and rhTRAIL4C7 were used. Since the signature peptides that provided the highest sensitivity and allowed discrimination between rhTRAILWT and rhTRAIL4C7 contained methionine residues, we oxidized these quantitatively to their sulfoxides by the addition of 0.25% (w/w) hydrogen peroxide. The final method has a lower limit of quantification of 20 ng/mL (ca. 350 pM) and was fully validated according to current international guidelines for bioanalysis. To show the applicability of the LC-MS/MS method for pharmacokinetic studies, we quantified rhTRAIL WT and rhTRAIL4C7 simultaneously in serum from mice injected intraperitoneally at a dose of 5 mg/kg for each protein. This is the first time that two variants of rhTRAIL differing by only a few amino acids have been analyzed simultaneously in serum, an approach that is not possible by conventional enzyme-linked immuno-sorbent assay (ELISA) analysis. © 2013 American Chemical Society.

PubMed | Erasmus Medical Center, University of Groningen and Bioanalytical Laboratory
Type: Journal Article | Journal: Analytical chemistry | Year: 2015

The administration of protein-based pharmaceuticals can cause the in vivo formation of antidrug antibodies (ADAs), which may reduce the efficacy of the therapy by binding to the protein drug. An accurate determination of the total and ADA-bound concentrations of the drug gives information on the extent of this immune response and its consequences and may help develop improved therapeutic regimens. We present an absolute quantitative method to differentiate between total, free, and ADA-bound drug for recombinant human alpha acid glucosidase (rhGAA) in plasma from patients suffering from Pompes disease. LC-MS/MS quantification of a signature peptide after trypsin digestion of plasma samples before and after an extraction of the total IgG content of plasma with protein G coated beads was used to determine the total and the ADA-bound fractions of rhGAA in samples from Pompe patients after enzyme infusion. The methods for total and ADA-bound rhGAA allow quantitation of the drug in the range of 0.5 to 500 g/mL using 20 L of plasma and met the regular bioanalytical validation requirements, both in the absence and presence of high levels of anti-rhGAA antibodies. This demonstrates that the ADA-bound rhGAA fraction can be accurately and precisely determined and is not influenced by sample dilution, repeated freezing and thawing, or extended benchtop or frozen storage. In samples from a patient with a reduced response to therapy due to ADAs, high ADA-bound concentrations of rhGAA were found, while in the samples from a patient lacking ADAs, no significant ADA-bound concentrations were found. Since protein G captures the complete IgG content of plasma, including all antidrug antibodies, the described extraction approach is universally applicable for the quantification of ADA-bound concentrations of all non-IgG-based biopharmaceuticals.

PubMed | Bioanalytical Laboratory
Type: Journal Article | Journal: Bioanalysis | Year: 2015

In bioanalysis of small molecules, the analyte concentration in the measured samples should reflect the concentration during sample collection. Precautions may be needed to prevent over- or under-estimation of the obtained result. This might require the addition of stabilizers to prevent degradation or nonspecific binding. For unstable drugs, it is essential to know how analytes can be stabilized before the start of the clinical study. Although the stabilization methods are well documented, the impact of the stabilization on the clinical workflow is not properly addressed. Already during method development, the clinical implications in terms of personnel safety, ease of use, training possibilities and staff capacity should be taken into account, and validation of the bioanalytical method should reflect collection procedures.

PubMed | University of Groningen and Bioanalytical Laboratory
Type: Journal Article | Journal: Analytical chemistry | Year: 2016

An LC-MS/MS-based method is described for quantitatively monitoring the in vivo deamidation of the biopharmaceutical monoclonal antibody trastuzumab at a crucial position in its complementarity determining region (CDR). The multiplexed LC-MS/MS assay using selected reaction monitoring (SRM) allows simultaneous quantitation of five molecular species derived from trastuzumab after tryptic digestion: a stable signature peptide (FTISADTSK), a deamidation-sensitive signature peptide (IYPTNGYTR), its deamidated products (IYPTDGYTR and IYPTisoDGYTR), and a succinimide intermediate (IYPTsuccGYTR). Digestion of a 50 L plasma sample is performed at pH 7 for 3 h at 37 C, which combines a reasonable (>80%) digestion efficiency with a minimal (<1%) formation of deamidation products during digestion. Rapid in vitro deamidation was observed at higher pH, leading to a (large) overestimation of the concentrations of deamidation products in the original plasma sample. The LC-MS/MS method was validated in accordance with international bioanalytical guidelines over the clinically relevant range of 0.5 to 500 g/mL with bias and CV values well below 15%. Deamidation of trastuzumab was observed in plasma both in a 56 day in vitro forced degradation study (up to 37% of the total drug concentration) and in samples obtained from breast cancer patients after treatment with the drug for several months (up to 25%). Comparison with a validated ELISA method for trastuzumab showed that deamidation of the drug at the CDR leads to a loss of recognition by the antibodies used in the ELISA assay.

Loading Bioanalytical Laboratory collaborators
Loading Bioanalytical Laboratory collaborators