Development of high-performance liquid chromatographic determination of salicylaldehyde isonicotinoyl hydrazone in rabbit plasma and application of this method to an in vivo study

An analytical methodology appropriate for the determination of the novel drug candidate salicylaldehyde isonicotinoyl hydrazone (SIH) in rabbit plasma has been developed and validated. Desirable chromatographic separation was achieved on a C18 column employing a mixture of phosphate buffer (0.01 M NaH2PO4 x 2 H2O with 2 mM EDTA, pH 6.0) and methanol (53:47; v/v) as the mobile phase. In order to develop a suitable sample preparation procedure, different methods have been tested (solid-phase extraction, liquid-liquid extraction, and protein precipitation). Protein precipitation using 0.1 M HClO4 and acetonitrile allowed the highest recoveries of the analyte to be reproducibly attained. The analytical methodology developed in this study was validated with respect to linearity (0.26-30.0 microg/mL), accuracy, precision, selectivity, recovery, and stability. A concentration of 0.26 microg/mL was determined as the LLOQ. The chromatographic method was applied to a preliminary plasma pharmacokinetic study. This study has provided the first information about the concentrations of SIH in plasma of a living subject. These results could have a significant impact on further progress in the development of this promising compound.     

Efficient robust estimates in parametric models

Summary Let {P ⁿ :}, an open subset ofR ^k , be a regular parametric model for a sample ofn independent, identically distributed observations. This paper describes estimates {T _n ;n1} of which are asymptotically efficient under the parametric model and are robust under small deviations from that model. In essence, the estimates are adaptively modified, one-step maximum likelihood estimates, which adjust themselves according to how well the parametric model appears to fit the data. When the fit seems poor,T _n discounts observations that would have large influence on the value of the usual one-step MLE. The estimates {T _n } are shown to be asymptotically minimax, in the Hájek-LeCam sense, for a Hellinger ball contamination model. An alternative construction of robust asymptotically minimax estimates, as modified MLE's, is described for canonical exponential families.This research was supported in part by National Science Foundation Grant MCS 75-10376     

A new assignment of IR vibrational modes in mullite

A new assignment of IR absorption bands of mullite is presented on the basis of empirical studies in the 1400–400 cm⁻¹ vibrational range of mullite-type compounds in the systems Al₂O₃–SiO₂, Al₂O₃–GeO₂, Ga₂O₃–GeO₂, and Al₂O₃–Me₂O, Ga₂O₃–Me₂O (Me=Na, K, Rb). The powder samples were prepared by heat treatment of sol–gel derived precursor powders and by reaction sintering of oxide powders. The FTIR powder spectra of Al–Si, Al–Ge, and Ga–Ge mullite compounds are characterized by three band groups, designated as (a), (b) and (c). Due to the lack of group (a) bands in the alkaline aluminate and gallate spectra, this high-energetic band group is assigned to Si---O and Ge---O stretching vibrations. Group (b) bands are essentially determined by Al---O and Ga---O stretching vibrations with Al and Ga on T sites in tetrahedral coordination and by T---O---T bending modes, while the low-energetic group (c) bands are due to Al---O and Ga---O stretching vibrations in octahedral structural units. Details of the vibrational modes are discussed on the basis of the deconvoluted spectra.     

Multiple Penalty Regression: Fitting and Extrapolating a Discrete Incomplete Multi-way Layout

The d iscrete multi-way layout is an abstract data type associated with regression, experimental designs, digital images or videos, spatial statistics, gene or protein chips, and more. The factors influencing response can be nominal or ordinal. The observed factor level combinations are finitely discrete and often incomplete or irregularly spaced. This paper develops low risk biased estimators of the means at the observed factor level combinations; and extrapolates the estimated means to larger discrete complete layouts. Candidate penalized least squares (PLS) estimators with multiple quadratic penalties express competing conjectures about each of the main effects and interactions in the analysis of variance decomposition of the means. The candidate PLS estimator with smallest estimated quadratic risk attains, asymptotically, the smallest risk over all candidate PLS estimators. In the theoretical analysis, the dimension of the regression space tends to infinity. No assumptions are made about the unknown means or about replication.     

Die Koordination von Ni2+ und Co2+ in Lösung von N,N-Dimethylacetamid

PMR spectra were obtained from bulk solvent molecules in anhydrous solutions of [M(DMA) ₆](ClO₄)₂ (M=Co, Ni) in N,N-dimethylacetamid (DMA). The free enthalpy of activation G _c ^* increases with increasing amount ofM ²⁺ as a result of the coordination of the cationsvia the oxygen atom resulting in a decrease of the bond length. Cobalt(II) acts as a weaker electron pair acceptor than nickel(II). The oxygen coordination is also shown by the different line broadening of the C-methyl protons as compared to that of the N-methyl protons.

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Simultaneous prediction regions

Summary Two new methods for constructing simultaneous prediction regions are the subject of this article. Both methods simultaneously assert a collection of prediction regions, one prediction region for each future observable of interest. Both methods have the same aims: to control the overall coverage probability of the simultaneous prediction region and to keep equal the coverage probabilities of the individual prediction statements that make up the simultaneous region. The latter property is called balance.The two approaches differ in their choice of critical values. For leading cases, the first method achieves the desired overall coverage probability and the desired balance up to errors of ordern ^–1, wheren is the size of the learning sample. The second method reduces both errors to ordern ^–2. Calculating critical values in the second approach usually relies on a bootstrap algorithm.If overall coverage probability and degree of balance are instead calculatedconditionally given the learning sample, the two methods show the same asymptotic performance. This result reflects intrinsic limits on the extent to which conditional coverage probabilities can be controlled in prediction.This research was supported in part by NSF Grant DMS-87-01426. Part of the work was done while the author was a guest of Sonderforschungsbereich 123 at Universität Heidelberg     

Central and Exchange Properties of Orthomodular Lattices

Criterions for the centre of an orthomodular lattice and a generalization of a result on the relation of commutativity due to S. P. GUDDER and R. H. SCHELP are given.     

CNDO/2 calculations of cluster models of zeolite crystals including their electrostatic field and its effect on the interacting molecules

Comparison of CNDO/2 calculations on zeolite clusters including the zeolite field, and ignoring it, indicate that inclusion of the field has no substantial effect on the physical characteristics of the cluster, but that molecules located inside the zeolite crystal are affected by this field.     

Thermodynamic study of lanthanide(III) complexes with bifunctional monophosphinic acid analogues of H4dota and comparative kinetic study of yttrium(III) complexes

New bifunctional H(4)dota-like ligands with three acetic acid and one phosphinic acid pendant arms and propionate (H(5)do3ap(PrA)) or 4-aminobenzyl (H(4)do3ap(ABn)) reactive groups bound to the phosphorus atom were investigated. Potentiometric studies showed that the ligands have a similar basicity to the parent H(4)dota and the stability constants of their complexes with sodium(i) and selected lanthanide(III) ions are also similar. Formation and acid-assisted decomplexation kinetics of yttrium(III) complexes with a series of H(4)dota-like ligands (H(4)dota and its phosphinic/phosphonic acid analogues) were studied and the reactions are sensitive to a slight modification of the ligand structure. The (2-carboxyethyl)phosphinic acid derivative H(5)do3ap(PrA) and the phosphonic acid ligand H(5)do3ap form complexes faster than H(4)dota. The most kinetically inert complex is that with H(4)do3ap(ABn). Rates of complexation and decomplexation can depend on the ability to transfer proton(s) outside/inside the complex cavity and, therefore, on the hydrophobicity of the ligands. The results demonstrate that the new bifunctional ligands are suitable for labelling biomolecules with yttrium(iii) radioisotopes for utilization in nuclear medicine.