Quantification of retinoid concentrations in human serum and brain tumor tissues

Retinoic acid signaling is essential for central nervous system (CNS) differentiation and appears to be impaired in tumors. Thus far, there are no established methods to quantify relevant retinoids (all-trans-retinoic acid, 9-cis-retinoic acid, 13-cis retinoic acid, and retinol) in human brain tumors. We developed a single step extraction and quantification procedure for polar and apolar retinoids in normal tissue, lipid-rich brain tumor tissues, and serum. This quantification procedure is based on high performance liquid chromatography (HPLC) with diode-array detection (DAD) using all-trans-acitretin as an internal standard and extraction by liquid–liquid partition with ethyl acetate and borate buffer at pH 9. Recovery with this extraction procedure was higher than earlier (two-step) liquid–liquid extraction procedures based on hexane, NaOH, and HCl. The overall quantification procedure was validated according to Food and Drug Administration (FDA) guidelines and fulfilled all criteria of accuracy, precision, selectivity, recovery, and stability. The overall method accuracy varied between −5.6% and +5.4% for serum and −3.8% and +6.2% for tissues, and overall precision ranged from 3.1% to 6.9% for serum and 2.1% to 8.3% for tissues (%CV batch-to-batch). The lower limit of quantification for all compounds in tumor tissue (and serum) was 3.9 ng g⁻¹ (ng mL⁻¹). Using this assay, photodegradation of the retinoids was evaluated and endogenous polar and apolar retinoids were quantified in sera and brain tumor tissues of patients and compared with serum and tonsil tissue concentrations of controls. It may thus serve as a suitable method for the characterization of retinoid uptake and metabolism in the respective compartments.     

Microscopic Interface Between Two Immiscible Electrolytes: A Parallelism to an Ultramicroelectrode

Abstract

Current-potential response of a small interface formed between two immiscible solutions of electrolytes is examined. The diameter of the contact area made in a thin glass wall separating two solvents is approximately 130 μm. Ion transport across the nitrobenzene-water interface is studied by addition of probe semi-hydrophobic ions such as tetramethylammonium, tetraethylammonium, picrate, choline and dodecylsulfate to either aqueous or nonaqueous phase. The voltammetric behavior observed with the microinterface generally resembles that of a solid microelectrode of a similar radius. The contribution of ohmic drop becomes less significant with decrease of the interface area. This phenomenon permits voltammetric and amperometric measurements without using a potentiostat, and the solvent resistance is of a lesser problem.     

A highly sensitive LC–MS/MS method for simultaneous determination of glycyrrhizin and its active metabolite glycyrrhetinic acid: Application to a human pharmacokinetic study after oral administration

A highly sensitive liquid chromatography tandem mass spectrometry (LC–MS/MS) method for simultaneous determination of glycyrrhizin (GL) and its active metabolite, glycyrrhetinic acid (GA), from human plasma was validated and applied to a human pharmacokinetic study. The analytes were extracted from human plasma using an Oasis MAX cartridge and chromatographic separation was performed on an Inertsil ODS‐3 column. The detection was performed using an API 4000 mass spectrometer operating in the positive electrospray ionization mode. Selected ion monitoring transitions of m /z 823 → 453 for GL and m /z 471 → 149 for GA were obtained. The response was a linear function of concentration over the ranges of 0.5–200 ng/mL for GL and 2–800 ng/mL for GA (both R ² > 0.998). Using this method, the pharmacokinetics of GL after single oral administration of a clinical dose (75 mg) to six healthy male Japanese volunteers were evaluated. GL was detected in the plasma of all subjects and the average peak concentration was 24.8 ± 12.0 ng/mL. In contrast, peak concentration of GA was 200.3 ± 60.3 ng/mL, i.e. ~8‐fold higher than that of GL. This is the first report clarifying pharmacokinetic profiles of GL and GA simultaneously at a therapeutic oral dose of a GL preparation.     

Synthesis and Characterization of Novel Biodegradable Di‐ and Tri‐Block Copolymers Based on Ethylene Carbonate Polymer as Hydrophobic Segment

Synthesis of novel amphiphilic biodegradable block copolymers based on ethylene carbonate is reported in this study. Polyethylene glycol monomethyl ether (MeO‐PEO) and polyethylene glycol (PEG) of varying molar masses are used as macro‐initiator for ring‐opening polymerization of ethylene carbonate in the presence of sodium stannate trihydrate as a heterogeneous transesterification catalyst. Earlier elution of block copolymer from macro‐initiator in size exclusion chromatography (SEC) indicated the successful synthesis of the block copolymers. Ratios of both types of blocks are varied systematically. Liquid chromatography at critical conditions is used for the analysis of the non‐critical individual blocks, and if there are any critical segments that are not attached to the non‐critical block. To the best of our knowledge, this is the first report on the synthesis of ethylene carbonate‐based amphiphilic block copolymers. Chromatographic critical conditions of the ethylene carbonate polymer are also reported for the first time. © 2017 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2017 , 55, 1887–1893     

Liquid-crystalline fork-like dendrons

ABSTRACT

Dendritic molecules having several rigid-rod moieties can be applied to induce liquid crystallinity for a variety of non-mesomorphic functional molecules such as metal complexes, nanoparticles, fullerenes and π-conjugated molecules when these dendritic molecules are covalently bonded to those non-mesomorphic molecules. These complex molecules are called supermolecular liquid crystals. Due to the cooperation of several mesogenic moieties, these dendritic molecules exhibit very stable liquid-crystalline (LC) phases. We have used fork-shaped LC dendrons having two or three rigid-rod moieties to induce liquid crystallinity for functional molecules such as interlocked molecules and π-conjugated molecules. In these fork-like molecules, the rigid-rod cores are attached to the 3,4,5-position of the phenyl moieties through flexible spacer, and these molecules are bonded to functional molecules through the 1-position. They basically form smectic LC phases, which induce the layered arrangement of functional moieties. Here we report on a new family of fork-like mesogens containing a hydrogen bonding moiety or an ionic group. They are designed to build supramolecular materials.     

Liquid Chromatograph Detector for Trace Analysis of Non-Volatile N-Nitroso Compounds

Abstract

A Thermal Energy Analyzer has been interfaced to a high performance liquid chromatograph. The hplc-TEA system can be used for analysis of nanogram amounts of N-nitroso compounds.     

Liquid–liquid extraction of copper(II) with substituted salicylideneanilines from sulfate media

The liquid–liquid extraction of copper(II) with Schiff bases in chloroform from sulfate media is studied for pH and concentration of the extractant. Stoichiometry coefficients of the extracted species are determined by the slope analysis method. With salicylideneaniline, the copper(II) is extracted as a mixed chelate complex, CuL₂HL. In the presence of substituent, the copper is extracted as simple chelates, CuL₂. The trends in the values of extraction constants were explained in terms of the nature of the substituents.     

Viscosity Mixing Rules for Binary Systems Containing One Ionic Liquid

In this work the applicability of four of the most commonly used viscosity mixing rules to [ionic liquid (IL)+molecular solvent (MS)] systems is assessed. More than one hundred (IL+MS) binary mixtures were selected from the literature to test the viscosity mixing rules proposed by 1) Hind (Hi), 2) Grunberg and Nissan (G–N), 3) Herric (He) and 4) Katti and Chaudhri (K–C). The analyses were performed by estimating the average (absolute or relative) deviations, AADs and ARDs, between the available experimental data and the predicted ideal mixture viscosity values obtained by means of each rule. The interaction terms corresponding to the adjustable parameters inherent to each rule were also calculated and their trends discussed.