High-performance liquid chromatographic determination of morphine and its 3- and 6-glucuronide metabolites: improvements to the method and application to stability studies

Improvements to previously reported methods for the determination of morphine, morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G) in human plasma are described. The improved methods involve the use of a solid-phase extraction cartridge and a chromatographic system which uses paired-ion reversed-phase high-performance liquid chromatography with a radially compressed column. Only one cartridge is used to prepare each sample for chromatography and each cartridge may be used for at least fourteen 1-ml plasma samples. The recovery is greater than 85%. The improvements to the method of sample pretreatment and in the chromatographic conditions have allowed determination of morphine, M3G and M6G in human plasma down to 13.3 nmol/l (coefficient of variation = 9.3%), 108 nmol/l (6.6%) and 41 nmol/l (6.7%), respectively, using ultraviolet detection alone. It was shown that all three compounds were stable in plasma for up to 101 weeks when stored at -20 degrees C.     

Mass spectrometric behavior of levoglucosan under different ionization conditions and implications for studies of cellulose pyrolysis

Pyrolysis-mass spectrometric studies of cellulose indicate low abundances of levoglucosan in the product spectrum compared to the yield values determined in more conventional types of pyrolysis studies. To examine the reason for these conflicting observation, levoglucosan was examined under different ion source conditions and ionization modes to ascertain the relative contributions of thermal degradation and ionization fragmention to the low abundances of the levoglucosan molecular ion. Low-energy electron ionization using conventional sample volatilization and molecular-beam sampling is compared to chemical ionization using methane, isobutane, and ammonia as reagent gases, and to field ionization and desorption. The mass spectrometric fragmentation patterns under the various systems indicate that studies of cellulose pyrolysis underestimate the amount of levoglucosan formed due to ionization fragmentation and thermal rearrangement reactions in the ion source. Several peaks, including m/z 126 and 144, are dominated by the contribution from the fragmentation of levoglucosan.     

The determination of phenol in urine by enzymatic hydrolysis/headspace gas chromatography

Summary A new method has been developed for the determination of phenol in urine in which the phenol conjugates are hydrolysed enzymatically and the liberated phenol is analysed by headspace chromatography. The results compare favourably with those obtained by the method of van Haaften and Sie in which acid hydrolysis is carried out in a heated GC precolumn. The enzymatic hydrolysis headspace technique appears to be very reliable and does not suffer from the disadvantages of precolumn acid hydrolysis.Since this paper was submitted, we have found a report on the enzymatic hydrolysis of phenyl glucuronide in urine followed by gas chromatographic analysis which seems to have been overlooked by later workers. The paper is by H. Desoille, T. F. Gandenzi-Britto and M. Philbert in Archives des Maladies Professionelles, de Medecine du Travail et de Securite Sociale (Paris),30 (3), 129 (1969).     

Chemistry of metal hydrides : XXI. Insertion of acetylenes into palladium hydrides

trans-Pd(NO₃)H(PCy₃)₂ (I) when treated with Et₄NCl forms the hydride trans-PdClH(PCy₃)₂ which in turn reacts with AgPF₆ in acetonitrile to give trans-[PdH(CH₃CN)(PCy₃)₂]PF₆ (III). Both I and III react smoothly with acetylenes containing one electron-withdrawing group to give alkenyl products. The geometry of the resulting alkenyl ligand implies that cis addition has occurred and that the hydridic hydrogen adds to the acetylenic carbon containing the electron-withdrawing group.Acetylenes containing two electron-withdrawing groups give mixtures from which both alkenyl and zerovalent acetylene compounds can sometimes be isolated. In the presence of proton sponge, monosubstituted acetylenes still give alkenyl products while those substituted with two electron-withdrawing groups give the zerovalent products in good yield. The relevance of these results to an understanding of the nature of the migratory insertion reaction is discussed.     

Isomerization of hydrocarbon ions. VIII—The electron impact induced decomposition of n-dodecane

The literature on the mass spectrometry of ²H and ¹³C labelled higher alkanes is reviewed and the decomposition behaviour of both the molecular and the fragment ions of n-dodecane, n-dodecane-1, 12-[¹³C₂] and n-dodecane-1,1,1,12,12,12-[²H₆] studied with special emphasis on metastable decompositions. It is shown that the elimination of alkane molecules and alkyl radicals from the n-dodecane molecular ion occurs primarily by simple splitting of the C? C bond. In addition, both small alkane molecule and alkyl radicals are eliminated with low probability from centreal parts of the molecular ion. The alkane elimination is less specific than the alkyl elimination. The methyl elimination shows an exceptionally high non-specificity, but is of negligible abundance in the 70 e V electron impact spectrum. The metastable ion spectra suggest, but do not prove unambiguously, that those small alkyl ions (with up to four carbon atoms) originating directly from the molecular ion, may be formed both by direct cleavage of the terminal groups and from central parts of the molecular ion. However, the majority of the small alkyl fragment ions in the 70 eV spectrum are formed by secondary decomposition explaining their apparent non-specific formation. The strikingly different fragmentation behaviour of even electron, [C_nH_2n+1]⁺, and odd electron fragment ions, results from differences in the product stabilities. Using collisional activation and metastable ion spectra it is shown that the odd electron fragments have the structure of the linear alkene (most probably the 1-alkene) molecular ion. In contrast to the molecular ions, alkyl fragment ions decompose with complicated skeletal rearrangements, which lead to substantial, but not complete, carbon randomization. The terminal hydrogen atoms, however, show little scrambling.     

An extremely active catalyst for the Negishi cross-coupling reaction

A new catalyst system for the Pd-catalyzed cross-coupling of organozinc reagents with aryl halides (Negishi coupling) has been developed. This system permits efficient preparation of hindered biaryls (tri- and tetra-ortho-substituted), functions effectively at low levels of catalyst, and tolerates a wide range of functional groups and heterocyclic substrates. A systematic study of ligand structure was performed and was correlated with catalyst activity.     

Effect of Niobium Modifications to PZT (53/47) Thin Films Made by a Sol-Gel Route

Niobium-modified lead zirconate titanate thin films (PNZT) with nominal compositions, Pb_(1–0.5x) (Zr_0.53 Ti_0.47)_1–x Nb _x O₃:x = 0.02–0.07, have been prepared using a diol based sol-gel route. Single-layer (0.5 m) films were fabricated on platinised silicon substrates by spin-coating. The effect of niobium additions with regard to phase development, microstructure, and ferroelectric and dielectric properties were investigated for different annealing temperatures. For comparison, unmodified PZT films were also prepared. Niobium substitution increased the crystallisation temperatures for perovskite PNZT phase formation. The values of remanent polarisation P _r and dielectric constant _r were found to decrease with the introduction of Nb. For example, in films heated at 700°C for 15 min, the P _r value of an unmodified PZT film was 31 C cm^–2, compared to 17 C cm^–2 for an x = 0.05 PNZT film, whilst respective relative permittivity values fell from 1190 to 600. The highest Nb concentration film, x = 0.07, did not display any switchable polarisation characteristics, which is consistent with high levels of intermediate pyrochlore phase.     

Pseudochelin A,a siderophore of Pseudoalteromonas piscicida S2040

A new siderophore containing a 4,5-dihydroimidazole moiety was isolated from Pseudoalteromonas piscicida S2040 together with myxochelins A and B, alteramide A and its cycloaddition product, and bromo- and dibromoalterochromides. The structure of pseudochelin A was established by spectroscopic techniques including 2D NMR and MS/MS fragmentation data. In bioassays selected fractions of the crude extract of S2040 inhibited the opportunistic pathogen Pseudomonas aeruginosa. Pseudochelin A displayed siderophore activity in the chrome azurol S assay at concentrations higher than 50 μM, and showed weak activity against the fungus Aspergillus fumigatus, but did not display antibacterial, anti-inflammatory or anticonvulsant activity.