Development of combinatorial chemistry methods for coatings: high-throughput adhesion evaluation and scale-up of combinatorial leads

Coupling of combinatorial chemistry methods with high-throughput (HT) performance testing and measurements of resulting properties has provided a powerful set of tools for the 10-fold accelerated discovery of new high-performance coating materials for automotive applications. Our approach replaces labor-intensive steps with automated systems for evaluation of adhesion of 8 x 6 arrays of coating elements that are discretely deposited on a single 9 x 12 cm plastic substrate. Performance of coatings is evaluated with respect to their resistance to adhesion loss, because this parameter is one of the primary considerations in end-use automotive applications. Our HT adhesion evaluation provides previously unavailable capabilities of high speed and reproducibility of testing by using a robotic automation, an expanded range of types of tested coatings by using the coating tagging strategy, and an improved quantitation by using high signal-to-noise automatic imaging. Upon testing, the coatings undergo changes that are impossible to quantitatively predict using existing knowledge. Using our HT methodology, we have developed several coatings leads. These HT screening results for the best coating compositions have been validated on the traditional scales of coating formulation and adhesion loss testing. These validation results have confirmed the superb performance of combinatorially developed coatings over conventional coatings on the traditional scale.     

Contamination of therapeutic human immunoglobulin preparations with apolipoprotein H (β2‐glycoprotein I)

Polyclonal immunoglobulin (Ig) concentrates are important biological medicinal products and the assurance of their quality and safety is crucial. In our present approach we used proteomic methods to check the purity of commercial Ig products of different origin. The experimental setup included nonreducing 2DE or DIGE combined with MALDI‐TOF and the thrombin generation assay, a routine safety test for pharmaceutical Ig preparations, and was complemented by a specific immunoassay. 2DE patterns displayed contaminations with trace amounts of human apolipoprotein H (Apo‐H), transferrin, albumin, and its fragments. In contrast to the latter, Apo‐H is a protein that is active in the coagulation cascade, and thus a potential involvement in thromboembolic events in vivo cannot be excluded. It was found by 2DE and MALDI‐TOF to be a contaminant of several Ig preparations. Spiking experiments of Ig preparations with pure Apo‐H demonstrated an Apo‐H concentration dependent increase in thrombin generation assay values. Traces of Apo‐H are possibly also contributing to unwanted side effects, as already known for factor XIa. The significance of Apo‐H contaminations for these side effects might be verified by detailed analyses of pharmacovigilance data.     

Influence of the steel powder type and processing parameters on the debinding of PM compacts with gelatin binder

Binders present an important part of the powder metallurgy technology as they are vital to provide efficient powder agglomeration and/or lubrication during shaping. At the same time, they have to be easily removed from the compacts during initial stages of sintering without any harmful effect for the base material, as well as for the environment. Therefore, behavior of gelatin as a binder for stainless- and tool-steel gas-atomised powder compacts was studied by thermal analysis and electron microscopy. Thermal analysis showed that peak mass-loss occurred in the range between 340 and 370 °C, depending on the base powder and heating rate. Risk for base powder oxidation at temperatures below 425 °C was detected. Based on the obtained results, it is recommended to perform debinding at ~425 °C after applying a heating rate of around 7.5 °C min^?1. Only in this way efficient enough binder removal can be obtained concurrently to avoiding base powder oxidation.     

Tutorial review on validation of liquid chromatography–mass spectrometry methods: Part II

This is the part II of a tutorial review intending to give an overview of the state of the art of method validation in liquid chromatography mass spectrometry (LC–MS) and discuss specific issues that arise with MS (and MS–MS) detection in LC (as opposed to the “conventional” detectors). The Part II starts with briefly introducing the main quantitation methods and then addresses the performance related to quantification: linearity of signal, sensitivity, precision, trueness, accuracy, stability and measurement uncertainty. The last section is devoted to practical considerations in validation. With every performance characteristic its essence and terminology are addressed, the current status of treating it is reviewed and recommendations are given, how to handle it, specifically in the case of LC–MS methods.     

Tutorial review on validation of liquid chromatography–mass spectrometry methods: Part I

This is the part I of a tutorial review intending to give an overview of the state of the art of method validation in liquid chromatography mass spectrometry (LC–MS) and discuss specific issues that arise with MS (and MS/MS) detection in LC (as opposed to the “conventional” detectors). The Part I briefly introduces the principles of operation of LC–MS (emphasizing the aspects important from the validation point of view, in particular the ionization process and ionization suppression/enhancement); reviews the main validation guideline documents and discusses in detail the following performance parameters: selectivity/specificity/identity, ruggedness/robustness, limit of detection, limit of quantification, decision limit and detection capability. With every method performance characteristic its essence and terminology are addressed, the current status of treating it is reviewed and recommendations are given, how to determine it, specifically in the case of LC–MS methods.     

Direct Catalytic Asymmetric Aldol Reaction of an α‐Azido Amide

A direct aldol reaction of an α‐azido 7‐azaindolinylamide, promoted by a Cu‐based cooperative catalyst, is documented. Aromatic aldehydes bearing an ortho substituent exhibited diastereodivergency depending on the nature of the chiral ligands used. Smooth reactions with ynals highlighted the broad substrate scope. A vicinal azido alcohol unit in the product allowed direct access to the corresponding aziridine and facile hydrolysis of the 7‐azaindolinylamide moiety furnished enantioenriched β‐hydroxy‐α‐azido carboxylic acid derivatives.