The Degradation Chemistry of Farglitazar and Elucidation of the Oxidative Degradation Mechanisms.

The chemical degradation of farglitazar (1) was investigated using a series of controlled stress testing experiments. Farglitazar drug substance was stressed under acidic, natural pH, basic, and oxidative conditions in solution. In the solid state, the drug substance was stressed with heat, high humidity, and light.

Comparative analysis of a neurotoxin from Calliostoma canaliculatum by on-line capillary isotachophoresis/1H NMR and diffusion 1H NMR.

NMR spectroscopy has been coupled on-line to capillary isotachophoresis (cITP) to enhance structural analyses of dilute charged species through separation and sample concentration. Microcoils, the most mass-sensitive NMR probes available, provide optimal detection for cITP/NMR. To evaluate the utility of cITP/NMR for natural product analysis, a homogenate of the hypobranchial gland from the marine snail Calliostoma canaliculatum containing a cationic neurotoxin (1, a disulfide-bonded dimer of 6-bromo-2-mercaptotryptamine) was studied.

Retention characteristics of protonated mobile phases injected into deuterated mobile phases in capillary liquid chromatography (LC) using on-line nuclear magnetic resonance (NMR) detection.

The behavior of protonated binary solvents injected into deuterated binary mobile phases in capillary LC is studied with NMR. Specifically, the solvent elution is followed on-flow with a capillary LC coupled to a 900 nL volume microcoil NMR probe. A range of identical composition 5% protonated (and 95% deuterated) solvents is injected into composition-matched deuterated mobile phases of CD(3)CN/D(2)O and CD(3)OD/D(2)O.

Characterization of a novel gastropod toxin (6-bromo-2-mercaptotryptamine) that inhibits shaker K channel activity.

A novel potassium channel antagonist has been purified from the defensive mucus secreted by Calliostoma canaliculatum, a marine snail found in the temperate coastal waters of the western Pacific. The toxin is expelled from the hypobranchial gland as part of a defensive response and is contained within a viscous matrix that minimizes dilution and degradation. The active compound was isolated by multistage microbore HPLC separations followed by bioactivity assays.

Mobile phase compensation to improve NMR spectral properties during solvent gradients.

A solvent compensation method based on flow injection analysis is used to obtain high quality nuclear magnetic resonance (NMR) spectra during solvent gradients. Using a binary solvent system containing D2O and CD3OD, NMR line broadening and chemical shift changes are observed with a 10% methanol per min solvent composition gradient. However, by creating a second equal but reverse gradient and combining the two solvent gradients before the NMR detector, the composition of solvent reaching the NMR flow cell is kept constant.

Micromixer-based time-resolved NMR: applications to ubiquitin protein conformation.

Time-resolved NMR spectroscopy is used to studychanges in protein conformation based on the elapsed time after a change in the solvent composition of a protein solution. The use of a micromixer and a continuous-flow method is described where the contents of two capillary flows are mixed rapidly, and then the NMR spectra of the combined flow are recorded at precise time points. The distance after mixing the two fluids and flow rates define the solvent-protein interaction time; this method allows the measurement of NMR spectra at precise mixing time points independent of spectral acquisition time.

NMR detection with multiple solenoidal microcoils for continuous-flow capillary electrophoresis.

Nuclear magnetic resonance (NMR) spectroscopy represents a promising on-line detector for capillary electrophoresis (CE). The inherent poor sensitivity of NMR mandates the use of NMR probes with the highest mass sensitivity, such as those containing solenoidal microcoils, for CE/NMR hyphenation. However, electrophoretic current degrades the resolution of NMR spectra obtained from solenoidal coils.

Microscale NMR.

NMR spectroscopy is increasingly being used to characterize microliter and smaller-volume samples. Substances at picomole levels have been identified using NMR spectrometers equipped with microcoil-based probes. NMR probes that incorporate multiple sample chambers enable higher-throughput NMR experiments.

Insights into the cITP process using on-line NMR spectroscopy.

Recently, capillary isotachophoresis (cITP) has been coupled on-line with nuclear magnetic resonance (NMR) to enhance analysis of dilute charged analytes through sample concentration and separation. This study focuses on the unique detection capabilities of NMR to noninvasively examine the cITP process and obtain diagnostic information. With their enhanced mass sensitivity, microcoil NMR probes provide optimal detection for cITP/NMR.

Capillary isotachophoresis/NMR: extension to trace impurity analysis and improved instrumental coupling.

Building upon its promising initial performance, the online coupling of capillary isotachophoresis (cITP) to nuclear magnetic resonance (NMR) is extended to trace impurity analysis. By simultaneously concentrating and separating dilute charged species on the basis of their electrophoretic mobility, cITP greatly facilitates NMR structural elucidation. cITP/NMR appears particularly attractive for identifying trace charged synthetic and natural organic compounds obscured by large excesses of other components.