Chromatographic aspects in high throughput liquid chromatography/mass spectrometry

Important parameters to consider when developing a liquid chromatography/mass spectrometry (LC/MS) method are buffer type and concentration, and column geometry. In the work presented here the choice of buffer for the analysis of basic compounds using a polar embedded phase (HyPURITYtrade mark ADVANCE) is illustrated for the analysis of tricyclic antidepressants. Method transfer from a 4.6 mm i.d. column to a 2.1 mm i.d. column is demonstrated for the analysis of triazines and anabolic steroids and their metabolites, with no change in selectivity and with added speed of analysis. Analysis of eight beta-blockers is achieved in 65 seconds by using a short 30 x 4.6 mm C18 column.     

Injection by Programmed Temperature Vaporization Injection (PTV) of Gaseous Samples for Gas Chromatography – Atomic Emission Spectrometry (GC-AED)

Programmed temperature vaporization injection (PTV) coupled to gas chromatography and atomic emission detector (AED) has been studied for large volume injection of gaseous samples. As examples of the effectiveness of the technique, the results of the analysis of a series of headspace samples of foods such as garlic and onion, and of landfill gases are presented. The volumes of gaseous samples reconcentrated varied from a few milliliters up to liters depending on analyte dilution, through focusing onto a sorbent trap, then rapid liberation into the GC-AED system by programmed thermal desorption. Despite the high carrier gas flow rates associated with direct PTV-GC, AED performance and sensitivity were unaffected. The detailed elemental information obtained from the PTV-GC-AED analyses was confirmed using a PTV coupled to a gas chromatograph with ion trap detector mass spectrometer as detector (PTV-GC-ITD/MS).     

A Basis for Orbital Symmetry Rules

The influence of molecular symmetry on reaction rates is examined with an approach in which reactions are viewed as electronic transitions between states of reacants and products (described, in turn by quasiadiabatic potential surface). The moleculer Hamiltonian is used to derive selection rules for these transitions. The complete Hamilatonian has no useful symmetery. Neglect of non-Born-Oppenheimer and spin-orbit terms (and of other angular momentum coupling terms) leads to an apporixmate Hamiltonian and to selection rules which from the basis of the Woodward-Hoffmann rules. This apporch provides an alternative to the adiabatic potantial surfaces, reaction coordinates, and transition state theory used in more familiar discussions of the Woodward-Hoffmann rules. Further, it provides a particulary clear method for discussing violations of these symmetry rules, and for differentiating concerted and nonconcerted reactions.     

Effect of metabolic inhibitors on vasopressin-stimulated transport systems in the toad bladder.

Vasopressin increases the permeability of receptor cells to water and, in tissues such as toad bladder, to solutes such as urea. While cyclic AMP appears to play a major role in mediating the effects of vasopressin, there is evidence that activation of the water permeability system and the urea permeability system involves separate pathways. In the present study, we have shown that inhibitors of oxidative metabolism (rotenone, dinitrophenol, and methylene blue) selectively inhibit either vasopressin-stimulated water flow or vasopressin-stimulated urea transport. There was no inhibition, however, when exogenous cyclic AMP was substituted for vasopressin, and little to no inhibition when the potent analogue 8-bromoadenosine 3',5'-cyclic monophosphate (8-Br-cAMP) was employed. Rotenone had no effect on adenylate cyclase activity or cyclic AMP levels within the cell; dinitrophenol decreased adenylate cyclase activity minimally. Additional studies with vinblastine and nocodazole, inhibitors of microtubule assembly, demonstrated an inhibition of vasopressin and cyclic AMP-stimulated water flow but showed no effect on urea transport. We would conclude that water and urea transport, as examples of hormone-stimulated processes, have different links to cell metabolism, and that in addition to cyclic AMP, a non-nucleotide pathway may be involved in the action of vasopressin.     

Alumina-catalyzed condensation of 2-methylquinoline with methanol

The alumina-catalyzed reaction of 2-methylquinoline with excess methanol at 500° produced a mixture of 2-ethyl-, 2-isopropyl-, and 2-isopropenylquinolines in yields of 10%, 7%, and 2%, respectively. A mechanistic interpretation of this reaction is presented.     

Über Polygermane. II [1]. Die Modifikationen des Dodecaphenylcyclohexagermans [2]

On Polygermanes. II. Modifications of Dodecaphenylcyclohexagermane Dodecaphenylcyclohexagermane (1) can be obtained from solutions pure (1a) , with 2 und 7 moles of crystal benzene (1b, 1c) and with 2 moles of crystal toluene (1d). Mass spectrum, ¹³C-nmr spectrum, assigned vibrational spectra (v_{s, Ge? Ge? Ge} = 220–235 cm^?1, v_{as, Ge? Ge? Ge} = 245–260 cm^?1) and crystal data are given. The crystal structure of 1c has been determined and refined to a R of 0.059. 1 forms a flattened Ge₆-chair (Ge-Ge distance 245.7(1) pm) with 6 axial and equatorial substituents respectively. The molecules of 1 approach spheres with a packing midway between a simple cubic and a cubic closest-packed arrangement.     

Synthesis,renal vasodilator and dopamine-sensitive adenylate cyclase activities of O-Methyl derivatives of 6-chloro-2,3,4,5-tetr ahydro-1-(4-hydroxyphenyl)-1H-3-benzazepin-7,8-diol (SK&F 82526)

The three possible mono-O-methyl derivatives of 6-chloro-2,3,4,5-tetrahydro-1-(4-hydroxyphenyl)-1H-3-benzazepin-7,8-diol (SK&F 82526) ( 1 ) have been synthesized to facilitate the isolation and characterization of metabolites of this compound and for biological testing. The syntheses generally involved preparation of appropriately substituted benzaldehydes, conversion of these to phenylacetic acids and use of these to N-acylate arylethanolamines. The phenylacetamides thus formed were reduced to amines and these were deprotected and cyclized to the desired final products. In one case deprotection followed cyclization. These compounds were tested as activators of dopamine-sensitive adenylate cyclase (a measure of DA-1 agonist activity) and as renal vasodilators. All three O-methyl derivatives were much less potent than 1 in cyclase activation and as renal vasodilators. Weak inhibition of adenyl cyclase was also observed for all three compounds and one showed weak renal vasoconstrictor activity. Preliminary investigation of the metabolism of 1 disclosed that two of the three monomethoxy compounds were formed in trace amounts in the rat and the dog. In a related investigation, the trimethoxy derivative of 1 was subjected to acid-catalyzed hydrolysis conditions. The relative ease of cleavage of methoxy groups was 7 > > 4′ > 8.