Synergic extraction of metals with α-acyl-d-camphor and optically active lewis bases

Solvent extraction of europium (III), zinc (II) cobalt (II) with α-acyl-d-camphor and optically active isomers of quinine and quinidine was studied in order to obtain information on chirality recognition based on adduct formation between a chiral metal chelate and optically active isomers. It was possible to differentiate clearly between the adduct formation of quinine and that of quinidine in the synergic extraction of cobalt and europium with 3-heptafluorobutyryl- d-camphor and cobalt with 3-trifluoroacetyl-d-camphor.     

Mechanisms of pharmacokinetic interaction between propranolol and quinidine in rats.

In order to study the mechanism of propranolol-quinidine interaction, the effects of quinidine on propranolol pharmacokinetics were examined in male Wistar rats. The concurrent oral administration of quinidine (10 mg/kg) markedly increased the plasma concentration of propranolol (2.5 mg/kg), and the area under the propranolol concentration-time curve increased about 3.6-fold. These results are consistent with previous observations in man and indicate the possible usefulness of the male Wistar rat as an animal model for investigating the mechanisms of the drug interaction. When propranolol was given intravenously, a concurrent administration of quinidine increased the apparent distribution volume of propranolol, mainly by decreasing its plasma protein binding. However, the systemic clearance of propranolol was not significantly altered by quinidine. Thus, quinidine increased the availability of oral propranolol from 13.8 +/- 2.2 to 44.2 +/- 4.6% (p less than 0.01). Furthermore, quinidine delayed the elimination of propranolol from the isolated perfused rat liver. These results indicate that quinidine reduces the presystemic elimination of propranolol in the liver, thereby increasing its systemic availability after oral administration.     

Diffusion of quinidine sulphate through polydimethylsiloxane membranes containing silica filler : I. Theoretical

The diffusion of quinidine sulphate through a polydimethylsiloxane film containing 20% SiO₂ filler was studied in a cell with two stirred compartments separating the film, taking into account all the forms (neutral, mono- and di-protonated) of quinidine in the buffered aqueous solutions of the cell compartments. The theoretical treatment leads to a relationship between the quinidine concentration across the film thickness as a function of the diffusion time, allowing for the chemical reactions in the cell compartments at constant pH, the solubility of quinidine in the polymer phase and the adsorption of quinidine onto the SiO₂ phase. A solution for large values of time is given, showing a linear dependence of In Δc on time.     

Sample preparation procedure for determination of dopamine sulfate isomers in human urine by high-performance liquid chromatography with dual-electrode electrochemical detection

We developed a procedure utilizing small columns of solid-phase extraction material for sample preparation for the determination of dopamine sulfate (DAS) isomers in human urine. Processed sample is then subjected to high-performance liquid chromatography (HPLC) with dual-series-electrode electrochemical detection. Dopamine 3-O-sulfate (DA-3-S) and dopamine 4-O-sulfate (DA-4-S) were determined using two different HPLC systems. The ratio of the urinary excretion rate of DA-3-S to DA-4-S was relatively constant, but the 24-h excretion rates of total DAS varied widely among individuals. This method should prove useful in future studies concerning the metabolic and physiologic roles of DAS isomers.     

Conformational analysis of quinine and its pseudo enantiomer quinidine: a combined jet-cooled spectroscopy and vibrational circular dichroism study

Laser-desorbed quinine and quinidine have been studied in the gas phase by combining supersonic expansion with laser spectroscopy, namely, laser-induced fluorescence (LIF), resonance-enhanced multiphoton ionization (REMPI), and IR-UV double resonance experiments. Density funtional theory (DFT) calculations have been done in conjunction with the experimental work. The first electronic transition of quinine and quinidine is of π-π* nature, and the studied molecules weakly fluoresce in the gas phase, in contrast to what was observed in solution (Qin, W. W.; et al. J. Phys. Chem. C2009, 113, 11790). The two pseudo enantiomers quinine and quinidine show limited differences in the gas phase; their main conformation is of open type as it is in solution. However, vibrational circular dichroism (VCD) experiments in solution show that additional conformers exist in condensed phase for quinidine, which are not observed for quinine. This difference in behavior between the two pseudo enantiomers is discussed.     

The Determination of Optical Isomers of 2-[3-(2-Chloro-Penoxyphenyl)]-Propionic Acid in Rat Plasma by High Performance Liquid Chromatography

Abstract

The optical isomers of dl-2-[3-(2-chlorophenoxy-phenyl)]-propionic acid in rat plasma is converted to the diastereomeric derivatives with (+)-2-aminobutane and then determined by high performance liquid chromatography using a Nucleosil NH₂ (10 μm) column and cyclohexane-ethyl acetate (5:1) as a mobile phase.

The time course of the optical isomers of this drug in rat plasma after oral administration was measured.

The proposed method is specific and reproducible for the determination of the optical isomers of this drug.     

Enantioseparation of 6-aminoquinolyl-N-hydroxysuccinimidyl carbamate tagged amino acids and other zwitterionic compounds on cinchona-based chiral stationary phases

The fluorescent tag 6-aminoquinolyl-N-hydroxysuccinimidyl carbamate (AQC; AccQ Fluor reagent kit from Waters) is a commercial N-terminal label for proteinogenic amino acids (AAs), designed for reversed-phase separation and quantification of the AA racemates. The applicability of AQC-tagged AAs and AA-type zwitterionic compounds was tested for enantiomer separation on the tert-butyl carbamate modified quinine and quinidine based chiral stationary phases, QN-AX and QD-AX employing polar-organic elution conditions. The investigated test analytes included the enantiomers of the positional isomers of isoleucine (Ile), threonine, homoserine, and 4-hydroxyproline. Furthermore, β-AAs, cyclic, and heterocyclic AAs including trans-2-amino-cyclohexane carboxylic acid and trans-2-aminocyclohexyl sulfonic acid, phenylalanine derivatives substituted with halides with increasing electronegativity and 3,4-dihydroxyphenylalanine, cysteine-related derivatives including homocysteic acid, methionine sulfone, cysteine-S-acetic acid, and cysteine-S-acetamide as well as a small range of aminophosphonic acids were enantioseparated. A mechanistic interaction study of AQC-AAs in comparison with fluoresceine isothiocyanate-labeled AAs was performed. The chiral and chemoselective recognition processes involved in enantiomer separation and retention was systematically discussed. Special emphasis was set on the influential factors exhibited by the chemistry, branching position, and spatial properties of the investigated zwitterionic analytes. The general interest to separate and distinguish between different types of branched-chained AAs and metabolic side products thereof lies in the toxicity of some of these compounds, which makes for instance allo–Ile an attractive candidate in disease-related biomarker research.

Studies on the metabolism and the detectability of 4-methyl-amphetamine and its isomers 2-methyl-amphetamine and 3-methyl-amphetamine in rat urine using GC-MS and LC-(high-resolution)-MS n

4-Methyl-amphetamine (1-(4-methylphenyl)propane-2-amine; 4-MA) and its isomers 2-methyl-amphetamine (2-MA) and 3-methyl-amphetamine (3-MA) belong to the group of amphetamine-type stimulants and of new psychoactive substances. Several studies showed similar potencies in releasing noradrenalin and dopamine, but higher potencies in releasing serotonin than amphetamine. In March 2013, the EU Council decided on an EU-wide control based on the European Monitoring Centre for Drugs and Drug Addiction risk assessment report documenting that 4-MA was sold as amphetamine on the illicit market and detected in several fatal cases. Therefore, 4-MA and its isomers should be covered by drug testing in clinical and forensic toxicology. The aims of the presented work were to study the metabolism and detectability of each isomer in urine samples. For metabolism studies, rat urine samples were isolated by solid-phase extraction without and after enzymatic cleavage of conjugates. The phase I metabolites were separated and identified after acetylation by gas chromatography–mass spectrometry (GC-MS) and/or liquid chromatography–high resolution-linear ion trap mass spectrometry (LC-HR-MS ⁿ ) and the phase II metabolites by LC-HR-MS ⁿ . From the identified phase I and II metabolites, the following main metabolic pathways were deduced: aromatic hydroxylation, hydroxylation of the phenylmethyl group followed by oxidation to the corresponding carboxylic acid, hydroxylation of the side chain, and glucuronidation and/or sulfation of the hydroxy and carboxy groups. CYP2D6 was involved in the aromatic hydroxylation. Finally, the intake of a commonly used dose of the MAs could be confirmed in rat urine using the authors’ GC-MS and the LC-MS ⁿ standard urine screening approaches. Differentiation of the isomers to confirm the intake of a specific isomer was possible with an additional workup in rat urine.     

Ion-pair extraction of some cinchona alkaloids with various chiral organic anions

Some cinchona alkaloids, the quinine/quinidine and cinchonine/cinchonidine pairs, are extracted by ion-pair formation with some chiral amino acids and d-camphorsulfonic acid. Their extraction behaviors are examined and the differences between the two isomers are compared. These alkaloids are extracted into chloroform in the pH range 4–7 as the 1:1 ion-pair with the organic acid. The relationship between the distribution ratio of the ion-pair and pH is discussed. In the pH range between the pK_a1 and pK_a2 values of these alkaloids, logarithmic plots of the distribution ratio are independent of pH. In this pH region, the extraction constants are determined and the differences caused by the ion-pair formation are discussed.     

化学衍生用于代谢物异构体质谱分析

内源性代谢物是机体生命活动的中间体和终产物,对其进行定性和定量分析在生命科学研究中具有重要意义.质谱能够同时提供化合物的定性和定量信息,已经成为一种通用的内源性代谢物分析技术.由于质谱是通过检测离子质荷比获取化合物组成信息,区分生物体内复杂多样代谢物同分异构体仍然是质谱分析亟待解决的难题之一.化学衍生通过放大同分异构体...     

Molecular Exclusion Separation of 1-Butene Isomers by a Robust Metal–Organic Framework under Humid Conditions

Separating n-butene and i-butene by adsorption is an energy-efficient alternative, but designing porous adsorbents that distinguish the subtle differences between the isomers is extremely challenging. Currently, adsorbents that can sieve 1-butene isomers and are stable enough to withstand humid gas mixtures are largely unmet. Herein, we propose a robust ultramicroporous metal–organic framework (MET-Fe) that can separate 1-butene isomers through molecular exclusion. The pore aperture size (4.6 Å) precisely matches the kinetic diameters of the isomers, as verified by static and kinetic adsorption experiments and theoretical calculations. Furthermore, dynamic breakthrough experiments confirmed the excellent separation performance, easy regeneration, and remarkable reusability of MET-Fe in both dry and humid conditions. With its high selectivity, large breakthrough capacity, and outstanding stability, MET-Fe provides an ideal platform for industrial butene isomers separation.     

Isolation of new quinidine metabolites and simultaneous determination of quinidine and its metabolites in blood and urine by direct injection HPLC analysis

Summary New quinidine metabolites, including 10,11-dihydrodiol quinidine N-oxide, 10,11-dihydrodiol quinidine and their glucuronides, were found in human urine. A quinidine monitoring HPLC method including these metabolites, is proposed by the direct injection of body fluid samples onto the precolumn for deproteinization followed by reverse phase separation in the analytical column with a column switching technique. The recovery of spiked quinidine and its metabolites in plasma was quantitative (98–102%) with good reproducibility (C.V.: 1.6–4.0%). Several clinical samples such as whole blood and urine were analyzed by the present method.     

Application of multivariate methods to the simultaneous Fourier Transform Infrared (FT-IR) spectrometric determination of stereo-isomers; quinine and quinidine

The two stereo-isomers; quinine and quinidine have been determined in their mixtures in the IR region using chemometric multivariate methods, principal component regression (PCR) and partial least squares (PLS). A training set of thirty synthetic binary mixture solutions in the possible combinations containing 0.0 - 4.0 and 4.0 - 0.0% w/v quinine and quinidine, respectively in chloroform was used to develop the multivariate calibrations. A validation set containing thirty synthetic binary mixtures of variable ratios in the range of 0.2 - 4.0 and 4.0 - 0.2% w/v for quinine and quinidine, respectively in chloroform was used to validate the developed calibrations. The results of analysis of the validation synthetic mixtures were found to be 100.5+/-0.44% (R.S.D.%=0.44) and 100.5+/-0.38% (R.S.D.%=0.38) for quinine and 100.1+/-0.67% (R.S.D.%=0.67) and 100.1+/-0.68% (R.S.D.%=0.68) for quinidine using PCR and PLS models, respectively.     

Conversion of Magnus salt into diamminedichloroplatinum(II) isomers in aqueous solution

The conditions inducing conversion of Magnus salt into diamminedichloroplatinum(II) isomers were studied. Syntheses of cis-diamminedichloroplatinum(II) and trans-diamminedichloroplatinum(II), which are used to prepare potassium or ammonium amminetrichloroplatinate(II), are described. The identity and structure of diamminedichloroplatinum(II) isomers were verified by elemental analysis, X-ray powder diffraction, and IR and UV spectroscopy. A workflow for preparing potassium or ammonium amminetrichloroplatinate(II) from diamminedichloroplatinum(II) isomers was developed. This workflow appreciably increases the product yield due to the return of unused Magnus salt to the main synthesis flow.     

Assay of the chiral organophosphate, soman, in biological samples

The anticholinesterase, soman, (CH3)3CC(H)CH3O(CH3)P(O)F, consists of four stereoisomers assigned as C(+/-)P(+/-)-soman in which C stands for chirality in the pinacolyl moiety and P for chirality at phosphorus. The four stereoisomers are separated by gas chromatography on an optically active Chirasil-Val column, synthesized and coated in house, or on a Chirasil-Val column identical with the commercially available column when combined with a Carbowax 20M column. This method in combination with an assay based on acetylcholinesterase inhibition shows that the two isomers which do not have anticholinesterase activity, i.e. C(+/-)P(+/-)-soman, are rapidly degraded in rat blood due to hydrolysis by phosphorylphosphatases. Epimeric soman isomers, e.g. C(+/-)P(-)-soman, can be separately assayed on a Carbowax or a CPSil 8 column, using 2H-labeled soman isomers as internal standards. 2H-labeled soman stereoisomers serve as internal standards in GC-assay of all four stereoisomers on Chirasil-Val. For work-up of the four stereoisomers from rat blood the sample is first stabilized by acidification to pH 4.2 at 0 degree C to suppress hydrolysis by phosphorylphosphatases, addition of aluminum ions for complexation of fluoride ions to prevent regeneration of C(+/-)P(-)-soman by free fluoride ions from soman-inhibited carboxylesterase, and addition of (CH3)3CCH2O(CH3)P(O)F to occupy covalent binding sites for C(+/-)P(-)-soman, before extraction with a Sep-Pak C18 cartridge and elution with ethyl acetate. Using a splitless or on-column injection technique and alkali flame ionization detection, the minimum detectable concentration is 30 pg/3-ml blood sample.     

Diffusion of quinidine sulphate through polydimethylsiloxane membranes containing silica filler : II. Evaluation of the permeability of neutral quinidine at various ph values and at 37°c

In this paper, experimental data on the diffusion of quinidine sulphate through a polydimethylsiloxane film containing SiO₂ filler are reported at pH = 1.18, 4, 7.6, 8, 10 and 11; all at T = 37°C. When these data are correlated with the theoretical equation of Part I for large times, a least squares procedure gives the values of the permeability and of the fraction of quinidine adsorbed onto the filler as a function of pH. The quinidine flux is compared with that in a glass porous disc cell. The behaviour of the two ceils considered is similar only for higher values of pH. The adsorption of quinidine onto the SiO₂ phase leads to permeabilities quite different from those obtained from simpler models.     

Efficient synthesis of an imidazole-substituted delta-amino acid by the integration of chiral technologies

Two methods to produce (2S)-5-amino-2-(1-n-propyl-1H-imidazol-4-ylmethyl)-pentanoic acid were investigated. Diastereoisomeric salt resolution, using the quinidine salt, gave the desired intermediate in 98% ee and 33% yield. Asymmetric hydrogenation of various substrates gave high conversions, with up to 83% ee. Integration of these two approaches via asymmetric hydrogenation of a quinidine salt substrate followed by crystallization provided the desired intermediate in 94% ee and 76% yield.     

Tribute to Prof. Roy Edward Bruns,Universidade Estadual de Campinas

Abstract

Arrhythmic patients treated with quinidine have been found to ingest caffeine from various sources. Caffeine interferes with the quantitation of quinidine in plasma samples. This method for determination of quinidine in plasma is based on high performance isocratic liquid chromatography with the use of a C-18 bonded reverse phase column at room temperature. Unlike some liquid chromatographic procedures for quinidine, caffeine does not interfere. Quinidine is extracted from alkalinized plasma into benzene. The benzene layer is removed and evaporated to dryness under nitrogen at 50 C. The residue is reconstituted with methanol and injected into the column. The mobile phase is 30/70 (v/v) mixture of methanol/0.4% glacial acetic acid. Analysis can be completed within 10 minutes. The procedure is sensitive (0.5mg/L) and is well reproducible (CV= 3.5% for a 2 mg/L concentration in plasma).     

对环芳烷二氯化产物组成的GC—MS表征

对环芳烷([2,2]Paracyclophane,简称PCP）是指苯环对位桥联的化合物,PCP及其氯代PCP的重要用途是通过升华、裂解、聚合等步骤沉积于物体表面形成聚合膜,该聚合膜具有透湿和透气小、抗化学腐蚀和抗辐射等优良性能[1,2].     

Measurement of cis and trans isomers of vitamin K1 in rat tissues by liquid chromatography with a C30 column

The purpose of this study was to validate a method for measuring vitamin K isomers in rat tissues by liquid chromatography (LC) with fluorescence detection after simple solvent extraction. This method uses separation on a C30 column, followed by zinc reduction and fluorescence measurement (243 nm, excitation; 430 nm, emission) to detect and quantitate vitamin K isomers. We were able to separate cis- and trans-vitamin K1 in methylene chloride extracts of homogenized rat livers and in hexane extracts of rat plasma. Tissue extracts were evaporated and rediluted with tetrahydrofuran-methanol (1 + 1) or methanol before being injected under isocratic conditions onto the LC column. Liver tissue of Fischer 344 rats fed a vitamin K1-containing diet ad libitum contained approximately 20 and 60 ng/g cis- and trans-vitamin K1, respectively. Mean recoveries of vitamin K1 isomers from spiked liver were 92 +/- 11% for cis-vitamin K1 and 106 +/- 5% for trans-vitamin K1. We recovered 96 +/- 8% of trans-vitamin K1 added at 1, 3, and 6 ng/mL to plasma (containing an endogenous level of 4 ng/g) from the same rats; we recovered 112 +/- 5% when trans-vitamin K1 was added to human serum (National Institute of Standards and Technology Standard Reference Material 968C). This direct method shows significant potential for the selective measurement of vitamin K1 isomers in tissues.