Reconstitution followed by non-targeted mid-infrared analysis as a workable and cost-effective solution to overcome the blending duality in milk powder adulteration detection.

Mid-infrared analysis of reconstituted milk is proposed as a feasible solution for the detection of milk powder adulteration regardless of the blending practice. To challenge the concept, skim milk powders were spiked with three of the most reactive/unstable of potential milk adulterants: semicarbazide hydrochloride, ammonium sulfate and cornstarch. To create the wet-blended set, a fraction of each sample was reconstituted and re-spray dried at laboratory scale with a benchtop spray dryer. Dry and wet-blended adulterated samples were reconstituted prior to mid-infrared measurement and projected onto a one-class classifier SIMCA model for reconstituted skim milk. Quantitative sensitivities, determined from the normalized orthogonal distances, were compared. Although the non-industrial spray drying introduced a spectroscopic bias, as revealed by the control samples, the non-targeted mid-infrared model showed comparable sensitivities for both blending practices once the main bias-rich spectral regions were removed, validating thereby the proposed concept.

A step-economical multicomponent synthesis of 3D-shaped aza-diketopiperazines and their drug-like chemical space analysis.

A rapid and atom economical multicomponent synthesis of complex aza-diketopiperazines (aza-DKPs) driven by Rh(i)-catalyzed hydroformylation of alkenylsemicarbazides is described. Combined with catalytic amounts of acid and the presence of nucleophilic species, this unprecedented multicomponent reaction (MCR) enabled the formation of six bonds and a controlled stereocenter from simple substrates. The efficacy of the strategy was demonstrated with a series of various allyl-substituted semicarbazides and nucleophiles leading to the preparation of 3D-shaped bicyclic aza-DKPs. Moreover, an analysis of their 3D molecular descriptors and "drug-likeness" properties highlights not only their originality in the chemical space of aza-heterocycles but also their great potential for medicinal chemistry.

Rapid detection of economic adulterants in fresh milk by liquid chromatography-tandem mass spectrometry.

A method to aid in the detection of the economically driven adulteration of fresh milk with a range of small, nitrogen containing compounds, including melamine, ammeline, ammelide, cyanuric acid, allantoin, thiourea, urea, biuret, triuret, semicarbazide, aminotriazine, 3- and 4-aminotriazole, cyanamide, dicyandiamide, guanidine, choline, hydroxyproline, nitrate, and a range of amino acids, has been developed. (15)N2-Urea is used as an internal standard. The adulteration of milk with exogenous urea has previously been difficult to detect because of the variation in the naturally occurring levels of urea in milk. However, by monitoring the contaminants biuret and triuret, which comprise up to 1% of synthetic urea, the adulteration of milk with urea-based fertilizer can be detected. We estimate that to be economically viable, adulteration of the order of 90-4000ppm of the above adulterants would need to be added to fresh milk. For most of the compounds, an arbitrary detection threshold of 2ppm is therefore more than sufficient. For biuret, a lower detection threshold, better than 0.5ppm, is desirable and the sensitivity for biuret and triuret can be improved by the post-column addition of lithium to create lithium adducts under electrospray ionisation. Sample handling involves a two-step solvent precipitation method that is deployed in a 96-well plate format, and the hydrophilic interaction liquid chromatography uses a rapid gradient (1.2min). Three separate injections, to detect the positively charged compounds, the negatively charged compounds and amino acids and finally the lithium adducts, are used. This rapid and qualitative survey method may be deployed as a second tier screening method to quickly reduce sample numbers indicated as irregular by an FTIR based screening system, and to direct analysis to appropriate quantification methods.

Quantitative assessment of the metabolic activation of alicyclic amines via aldehyde.

INTRODUCTION: Recently it has been reported that some drugs that produce reactive intermediates may cause clinical adverse effects following covalent binding to biomacromolecules. For example, Schiff base production mediated by aldehyde is a possible mechanism of drug-protein adducts. However, because thiols do not trap aliphatic aldehydes via hemiacetal or hemiaminal, the glutathione-trapping method cannot be used to determine the covalent bindings of the Schiff base. METHODS: We established a quantitative method to determine covalent binding mediated by aldehydes via hemiaminal or hemiacetal using non-radiolabeled compound and [(14)C]semicarbazide as a hard-trap agent with unique post-incubation. RESULTS: The trapped aldehyde obtained from the post-incubation was almost equivalent to the covalent binding of the radiolabeled tool compound. Our novel method showed its usefulness in quantitative detection of aldehyde's covalent binding ability by several reagents with alicyclic amine and launched drugs as control. DISCUSSION: The post-incubation method is useful for screening newly synthesized compounds to quantitatively assess the bioactivation of aldehydes descending from alicyclic amines.