A Diagnostic Nitrosamine Detection Approach for Pharmaceuticals by Using Tandem Mass Spectrometry Based on Diagnostic Gas-Phase Ion-Molecule Reactions.

-Nitrosamines are strictly regulated in pharmaceutical products due to their carcinogenic nature. Therefore, the ability to rapidly and reliably identify the -nitroso functionality is urgently needed. Unfortunately, not all ionized -nitroso compounds produce diagnostic fragment ions and hence tandem mass spectrometry based on collision-activated dissociation (CAD) cannot be used to consistently identify the -nitroso functionality.

Identification and quantitation of isomeric pneumococcal polysaccharides by partial chemical degradation followed by mass spectrometry.

Quantitation of isomeric pneumococcal polysaccharides in vaccines is a challenging task due to mixture complexity, their low quantities, and identical monosaccharide compositions. Differentiation and quantitation of isomeric pneumococcal polysaccharides were investigated here based on a partial chemical degradation mass spectrometry approach to generate an oligosaccharide marker for one isomer, and not the other. Mild base conditions were successful at generating unique ions for the isomers with the weakest glycosidic bonds, while strong base and acid conditions were successful at generating unique ions for the more stable isomers.

Design and Study of PEG Linkers That Enable Robust Characterization of PEGylated Proteins.

Several PEGylated therapeutic proteins are approved drugs, and more are under development. However, the synthesis and characterization of these bioconjugates, especially heterogeneous mixtures of PEGylated proteins, are challenging. The present study focuses on the development of PEG linkers that can be installed through biocatalytic route and render much simpler and insightful analytical characterization of PEG-protein conjugates.

Integration of a Multichannel Pulsed-Valve Inlet System to a Linear Quadrupole Ion Trap Mass Spectrometer for the Rapid Consecutive Introduction of Nine Reagents for Diagnostic Ion/Molecule Reactions.

Gas-phase ion/molecule reactions have been used extensively for the structural elucidation of organic compounds in tandem mass spectrometry. Reagents for ion/molecule reactions can be introduced into a mass spectrometer via a continuous flow apparatus or through a pulsed inlet system. However, most of these approaches enable the use of only a single reagent at a time.

Differentiation of Deprotonated Acyl-, -, and -Glucuronide Drug Metabolites by Using Tandem Mass Spectrometry Based on Gas-Phase Ion-Molecule Reactions Followed by Collision-Activated Dissociation.

Glucuronidation, a common phase II biotransformation reaction, is one of the major and metabolism pathways of xenobiotics. In this process, glucuronic acid is conjugated to a drug or a drug metabolite via a carboxylic acid, a hydroxy, or an amino group to form acyl-, -, and/or -glucuronide metabolites, respectively. This process is traditionally thought to be a detoxification pathway.

Spin-Spin Coupling Between Two meta-Benzyne Moieties In a Quinolinium Tetraradical Cation Increases Their Reactivities.

The reactivity of a carbon-centered σ,σ,σ,σ-type singlet-ground-state tetraradical containing two meta-benzyne moieties was examined in the gas phase. Surprisingly, the tetraradical showed higher reactivity than its individual meta-benzyne counterparts. The reactivity of meta-benzynes is controlled by their (calculated) distortion energy ΔE , singlet-triplet spitting ΔE , and electron affinity (EA ) of the meta-benzyne moiety at the transition state geometry for hydrogen-atom abstraction reactions.

Differentiating Isomeric Deprotonated Glucuronide Drug Metabolites via Ion/Molecule Reactions in Tandem Mass Spectrometry.

Isomeric O- and N-glucuronides are common drug metabolites produced in phase II of drug metabolism. Distinguishing these isomers by using common analytical techniques has proven challenging. A tandem mass spectrometric method based on gas-phase ion/molecule reactions of deprotonated glucuronide drug metabolites with trichlorosilane (HSiCl) in a linear quadrupole ion trap mass spectrometer is reported here to readily enable differentiation of the O- and N-isomers.

Absolute configuration assignment of (+)-fluralaner using vibrational circular dichroism.

The absolute configurations of the separated enantiomers of fluralaner, a racemic animal health product used to prevent fleas and ticks, have been assigned using vibrational circular dichroism (VCD). The crystallographic structure of the active enantiomer (+)-fluralaner has previously been shown to have the (S) configuration using small molecule crystallography. We sought a faster analytical method to determine the absolute configuration of the separated enantiomers.

Identification of Carboxylate, Phosphate, and Phenoxide Functionalities in Deprotonated Molecules Related to Drug Metabolites via Ion-Molecule Reactions with water and Diethylhydroxyborane.

Tandem mass spectrometry based on ion-molecule reactions has emerged as a powerful tool for structural elucidation of ionized analytes. However, most currently used reagents were designed to react with protonated analytes, making them suboptimal for acidic analytes that are preferentially detected in negative ion mode. In this work we demonstrate that the phenoxide, carboxylate, and phosphate functionalities can be identified in deprotonated molecules by use of a combination of two reagents, diethylmethoxyborane (DEMB) and water.

Identification of Protonated Sulfone and Aromatic Carboxylic Acid Functionalities in Organic Molecules by Using Ion-Molecule Reactions Followed by Collisionally Activated Dissociation in a Linear Quadrupole Ion Trap Mass Spectrometer.

Gas-phase reactivity of protonated model compounds with different functional groups toward trimethoxymethylsilane (TMMS) was studied to explore the utility of this reagent in mass spectrometric identification of specific functionalities for potentially rapid characterization of drug metabolites. Only protonated analytes with a carboxylic acid, a sulfone, or a sulfonamide functionality formed diagnostic adducts that had lost a methanol molecule upon reactions with TMMS. Collisionally activated dissociation (CAD) of these methanol-eliminated adduct ions (MS experiments) produced characteristic fragment ions of m/z 75, 105, and 123 for sulfones, while an additional methanol elimination was observed for carboxylic acids and sulfonamides.

Gas-phase ion-molecule reactions for the identification of the sulfone functionality in protonated analytes in a linear quadrupole ion trap mass spectrometer.

Rationale: The oxidation of sulfur atoms is an important biotransformation pathway for many sulfur-containing drugs. In order to rapidly identify the sulfone functionality in drug metabolites, a tandem mass spectrometric method based on ion-molecule reactions was developed.

Methods: A phosphorus-containing reagent, trimethyl phosphite (TMP), was allowed to react with protonated analytes with various functionalities in a linear quadrupole ion trap mass spectrometer.

Mass spectrometric identification of the N-monosubstituted N-hydroxylamino functionality in protonated analytes via ion/molecule reactions in tandem mass spectrometry.

Rationale: N-Monosubstituted hydroxylamines correspond to an important class of metabolites for many bioactive molecules. In this study, a tandem mass spectrometric method based on ion/molecule reactions was developed for the identification of compounds with the N-monosubstituted hydroxylamino functionality.

Methods: The diagnostic ion/molecule reaction occurs between protonated analytes with 2-methoxypropene (MOP) inside a linear quadrupole ion trap mass spectrometer.

Metamagnetic behaviour in a new Cu(II)Re(IV) chain based on the hexachlororhenate(IV) anion.

A new chloro-bridged heterobimetallic Cu(II)Re(IV) chain of formula {Cu(pyim)(Him)2ReCl6}n·MeCN (·MeCN) has been prepared and magnetostructurally characterised. Compound is the first example of the [Re(IV)Cl6](2-) anion acting as a metalloligand towards a paramagnetic metal ion.

A survey of Chinese herbal ingredients with liver protection activities.

A literature survey was conducted on herbs, their preparations and ingredients with reported liver protection activities, in which a total of 274 different species and hundreds of active ingredients have been examined. These ingredients can be roughly classified into two categories according to their activities: (1) the main ingredients, such as silybin, osthole, coumarin, glycyrrhizin, saikosaponin A, schisandrin A, flavonoids; and (2) supporting substances, such as sugars, amino acids, resins, tannins and volatile oil. Among them, some active ingredients have hepatoprotective activities (e.