Analysis of LK-157 in Plasma by LC–MS–MS: Application to Studies of Pharmacokinetics and Degradation Pathways in Rats and Dogs

Multiple-species plasma-stability testing and pharmacokinetic studies in rats and dogs were performed on LK-157, a novel 10-ethylidene tricyclic carbapenem and potent inactivator of β-lactamases of classes A, C, and D. An LC–MS–MS method was developed and validated for analysis of LK-157 in rat and dog plasma. Separation was achieved on a C₁₈ column by gradient elution. The lower limit of quantification for LK-157 in plasma was 50 ng mL^?1. Intra-day and inter-day precision were <12.5 and <11.8%, respectively. When degradation of LK-157 was assessed in buffer solutions and in rat, dog, and human plasma, the compound was found to be stable in pH 7.0–9.0 phosphate buffer for 24 h at room temperature, and in human plasma for 60 min at 37 °C. The stability of LK-157 was species-dependent. Results from study of in vitro metabolism showed that the enzymes liver cytochrome P450 and uridine diphosphate glycosyltransferase do not metabolize LK-157. LC–MS–MS was also successfully applied to a pharmacokinetic study. The pharmacokinetics of LK-157 after bolus intravenous administration (10 mg kg^?1) to Wistar rats and Beagle dogs was described by a two-compartment pharmacokinetic model. Human pharmacokinetic data were extrapolated from dog pharmacokinetic data. The extrapolated human terminal-phase half-life of LK-157 was 2.3 h. Stability and pharmacokinetic data for LK-157 are in agreement with results for other inactivators of β-lactamases.     

Combining solid-phase preconcentration, capillary electrophoresis and off-line matrix-assisted laser desorption/ionization mass spectrometry: intracerebral metabolic processing of peptide E in vivo

The in vivo metabolism of peptide E was studied in the anesthetized rat using a combination of microdialysis sampling, solid-phase preconcentration capillary electrophoresis and imaging matrix-assisted laser desorption/ionization mass spectrometry (MALDI/MS). The metabolic profile of peptides identified by MALDI/MS showed that the primary enzymatic activity for degradation of peptide E was due to carboxypeptidases and, to a lesser extent, aminopeptidases and some trypsin-like endopeptidases. Over 75 metabolic fragments were detected from the action of these enzymes in vivo.     

Micro-Electrospray: Zeptomole/attomole per microliter sensitivity for peptides

The micro-electrospray ionization source has been optimized for the specific analysis of neuropeptides such as neurotensin and methionine enkephalin. The source has the option of integrating nanoliter flow-rate desalting and preconcentration techniques into the micro-electrospray spray needle, eliminating post-column dead volumes. For neurotensin, the most sensitive neuropeptide analyzed thus far in this work, the injection of 10 μL of a solution containing 320 zeptomolesy/gmL gave an [M + 3H]⁺³ ion at m/z 558.4 with S/N of > 8∶1. The MS/MS analysis of this peptide for the fragment ion at m/z 578.9 gave a S/N > 20∶1 for a solution containing 32 attomoles/μL.     

A simple acid digestion method for the determination of ten elements in ambient aerosols by flame atomic absorption spectrometry

A method is presented for multi-element determinations in ambient aerosols collected on Whatman 41 filter paper. Subsections of filters are exposed to vapor phase attack by nitric and hydrofluoric acids, and complete dissolution is accomplished by a mixture of nitric and perchloric acids at high temperatures in quartz tubes. The residue is taken up in dilute nitric acid and processed directly by standard additions with a flame atomic absorption spectrometer. The method was tested on NBS Coal Fly Ash, SRM 1633, and found to yield accurate results.     

Use of HPTLC for Quantitative Evaluation of Inulin in Food Products

JPC – Journal of Planar Chromatography – Modern TLC - HPTLC and HPLC—MS methods have been developed for quantitative determination of inulin in food products. Samples were applied...     

Systematic synthesis and characterization of the derivative complexes of the tetrafluoroaminechromate(III) Anions. — crystal structure of the (en-H2)[CrF4(en)]Cl

Summary The new complexes (aa-H₂)[CrF_4(aa)]Cl, where aa = ethylenediamine, 1,2-diaminopropane or 1,2-diaminocyclohexane, have been systematically synthesized and characterized. The crystal structure of (en-H₂)[CrF₄(en)]Cl (en = ethylenediamine) has been resolved indicating that the four fluorine atoms are ligands and the chloride is ionic. The cation is the diprotonated ethylenediamine ligand. Synthesis of the analogous complex with 1,3-diaminopropane (tn) failed. The hydrolysis of these complexes with concentrated HBr give compounds of formula [CrF₂(H₂O)₂(aa)]Br, which upon solid phase heating yield the dehydrated [CrF₂Br(H₂O)(aa)].     

High-volume sampling of airborne polychlorobiphenyls with amberlite xad-2 resin

Polyurethane foam, polyurethane foam coated with DC-200, Florisil, and Amberlite XAD-2 resin have been evaluated in a small-scale comparative study of their ability to sample airborne polychlorobiphenyls. XAD-2 resin has an excellent collection efficiency for tetrachlorobiphenyl at 1 l min^-1 flow rates and is also suitable for high-volume air sampling. A high-volume air sampler was modified to sample both particulate and vapor-phase polychlorobiphenyls by incorporating the XAD-2 resin behind a glass fiber filter. When the sampling system was operated at a flow rate of 0.7 m³ min^-1 for 24 h, the collection efficiencies for tetrachlorobiphenyl and Aroclor 1221 were 96.5% and 83.0%, respectively.     

Elemental analysis of water and air solids by neutron activation analysis

Instrumental neutron activation analysis was used to determine the elemental concentrations in water and air solid samples collected on Nuclepore and Whatman filters from the Walker Branch Watershed. The results from this study show that the trace element concentrations removed by water from the watershed vary seasonally, as well as geographically. The data point up the usefulness and versatility of absolute neutron activation analysis. The NBS Standard Orchard Leaves was assayed in a similar manner, and good agreement was obtained between results here and standard values.