Identification of the secondary degradates of L-648,548 in an animal health formulation.

L-648,548 is a semisynthetic analog of avermectin. During stability investigations of this compound in an animal health formulation, two new degradates were discovered. These degradates (L-648,548 phenol and its 8,9-Z isomer) were identified as the reaction products of 5-oxo-L-648,548 formed by oxidation of L-648,548. Addition of base to the reaction medium containing 5-oxo-L-648,548 was found to catalyze the formation of L-648,548 phenol via a postulated dehydration by an E1cb elimination followed by the rapid tautomerization of the C5 carbonyl. Photolysis of L-648,548 phenol with visible light (including ambient laboratory lighting) was found to readily produce 8,9-Z-L-648,548 phenol. This transformation was confirmed to be exclusively a photoinduced process.

Comparative evaluation of bone suture anchor to bone tunnel fixation of tibialis anterior tendon in cadaveric cuboid bone: a biomechanical investigation.

A multiphase biomechanical study was performed using human tibialis anterior tendons and cuboid bones, comparing the fixation of the tendon to the bone using bone anchors and bone tunnels. Twenty-six specimens were tested for ultimate load to failure comparing Mitek Superanchor fixation with no. 1 and no. 5 braided polyethelyne suture to bone tunnel fixation. Mitek Superanchor with no. 5 suture failed at 223 N, compared with Mitek Superanchor with no. 1 suture at 134 N and bone tunnel at 143 N (P = 0.033). Mitek with no. 1 suture versus bone tunnel was not significantly different. The Mitek with no. 5 suture failed at the tendon/suture interface (75%), the Mitek with no. 1 suture failed at the suture/anchor interface (56%), and bone tunnel fixation failed most commonly by fracture of the tunnel (76%). This study is the first biomechanical analysis of the pullout strengths of bone tunnels or suture anchors in the cuboid bone. We have shown that the suture anchor has a pullout strength comparable or superior to a conventional bone tunnel in an in vitro situation. We believe it is a viable alternative to fixation of the tibialis anterior tendon to the cuboid when there is insufficient tendon length or failure of the bone tunnel.

Isolation and characterization of the major equilibrium product of FK-520.

The existence of an isomeric form in equilibrium with the major component of FK-520 in polar solutions has been demonstrated. This minor component has been isolated in high yield and purity by a novel crystallization strategy and preparative HPLC. The equilibrium product was characterized by NMR and MS.

Isolation and identification of impurities in L-696, 229 drug substance.

Two low level impurities in 3-[2-(2-benzoxazolyl)ethyl]-5-ethyl-6-methyl-2(1H)-pyridinone drug substance (L-696,229) have been isolated by a combination of preparative HPLC, solid-phase extraction and liquid-liquid extraction. They were identified as 3-[2-(2-benzoxazolyl)ethyl]-5-ethyl-6-(2-phenylethyl)-2(1H)-pyridinone (I) and 6,6'-(2-phenyl-1,3-propanediyl)bis[3-[2-(2-benzoxazolyl)ethyl]-5-ethyl-2(1H)-pyridinone] (II) by mass spectrometry and by their (13)C and (1)H-NMR spectra.

Environmental semivolatiles and nonvolatiles analysis by hyphenated spectral techniques.

Environmental sample extracts contain a variety of volatile and nonvolatile organic compounds exhibiting a range of polarities and concentrations. Although gas chromatography/mass spectrometry (GC/MS) is the method of choice thus far for such analyses, this technique used alone cannot adequately characterize the volatiles in such samples and is not amenable to environmental nonvolatiles. A more complete characterization of environmental and hazardous waste samples is required to assess the dangers posed to the nation's groundwater by hazardous waste dumps. Online spectral confirmation by directly linked GC/Fourier transform infrared (FTIR)/MS is shown to provide useful structural information on environmental volatiles in hazardous wastes, even when the analyte's spectrum is not in either spectral database. This information can lead to biological-hazard estimation. The diffuse reflectance Fourier transform infrared (DRIFT) technique, used in conjunction with thermospray MS or fast atom bombardment (FAB) MS, provides confirmed identifications or confirmed compound class assignments of organic nonvolatiles in solid wastes. This is believed to be the first report of spectral confirmation (identification or functionality) of organic volatiles and nonvolatiles in environmental samples.

Thermospray LC/MS/MS analysis of wastewater for disperse azo dyes.

Primary effluent from a municipal wastewater treatment plant was used as the feed in bench scale activated sludge systems. These systems were spiked with disperse azo dyes at 1 mg 1-1 and 5 mg 1-1 levels and were sampled at various points in the process. Samples were analysed by high performance liquid chromatography with UV = visible detection and by thermospray ionization MS and tandem mass spectrometry (MS/MS) using direct injection or via column chromatography. The tandem mass spectrometry techniques were used both for method development purposes and for the specificity and extra information these techniques can provide. The investigation of the fate of disperse azo dyes in the activated sludge process was a major feature of this study. Major degradation products have been identified by tandem mass spectrometry analyses of these wastewaters. Precision and accuracy data generated by the thermospray tandem mass spectrometry technique are compared to those derived from the high performance liquid chromatography/UV-visible method.

Sequence analysis of polypeptides by collision activated dissociation on a triple quadrupole mass spectrometer.

A new approach to the direct sequencing of oligopeptides in complex mixtures is described. Mixtures of [2Ho]/[2H3]-N-acetylated and N,O-permethylated peptides are analyzed by collision activate dissociation on a triple quadrupole mass spectrometer using isobutane chemical ionization. Analysis of the collision activated dissociation spectra enables peptide sequences to be deduced. Use of electron capture negative chemical ionization for the sequence analysis of neuropeptides at the picomole level is also described.

A competency-based curriculum for training middle-level community--clinical psychologists.

The focus of this paper is to delineate the basic skills that might be appropriate for a community--clinical psychologist.. The need for competent professionals to deliver mental health services has exceeded the capacity of existing training programs. Current training emphasis is aimed at providing a community--clinical psychologist on the middle level who would have a set of skills or competencies that would easily identify him as a psychologist