Simultaneous determination of glycols based on fluorescence anisotropy

Simultaneous determination of non-fluorescent glycols in mixtures without separation or chemical transformation steps is described. Two methods based in the measure of fluorescence anisotropy of a probe such as fluorescein dissolved in the analyte or analyte mixtures are described. In the first method, the anisotropy spectra of pure and mixtures of analytes are used to quantitative determination (if the fluorophor concentration is in a range where fluorescence intensity is proportional to concentration). In the second method, a calibration curve anisotropy-concentration based on the application of the Perrin equation is established. The methods presented here are capable of directly resolving binary mixtures of non-fluorescent glycols on the basis of differences on the fluorescence anisotropy of a fluorescence tracer. Best analytical performances were obtained by application of the method based on Perrin equation. This method is simple, rapid and allows the determination of mixtures of glycols with reasonable accuracy and precision. Detection limits are limited by the quantum yield and anisotropy values of the tracer in the solvents. Recovery values are related to the differences in anisotropy values of the tracer in the pure solvents. Mixtures of glycerine/ethylene glycol (GL/EG), ethylene glycol/1,2-propane diol (EG/1,2-PPD) and polyethylene glycol 400/1,2-propane diol (PEG 400/1,2-PPD) were analysed and recovery values are within 95-120% in the Perrin method. Relative standard deviation are in the range 1.3-2.9% and detection limits in the range 3.9-8.9%.     

Quantitative determination of diethylene glycol contamination in pharmaceutical products

A simple, rapid, and reliable method was developed for the quantitative determination of diethylene glycol (DEG) in pharmaceutical products using capillary gas chromatography with flame ionization detection. The method uses ethylene glycol as internal standard and allows for the separation of propylene glycol and DEG. The assay was linear in a DEG concentration range between 1.0 and 10.00 mg/mL, with coefficients of variation of 2.3-4.4% for the tested concentrations. Quantitation and detection limits, respectively, were 1.0 mg/mL and 0.15 mg/mL diethylene glycol. The method was used to analyze 3 pharmaceutical products possibly contaminated with diethylene glycol, of which one was suspected of causing intoxication and death in children. Infrared spectroscopy was used to confirm the identity of diethylene glycol. This analytical methodology is proposed for evaluation of pharmaceutical products containing glycols to prevent intoxication and for security level verification.     

Reversible protection of oligomeric ethylene glycols by bis (2,4-dinitrophenylation) and basic ethanolysis

Bis-(2,4-dinitrophenyl)glycols are stable in the presence of triethylamine but undergo ethanolysis in the presence of hydroxide ions. The quantitative removal of the DNP blocking group allows an integrated scheme to pure glycols from commercially available polyethylene glycol mixtures

1 Mixtures of ethylene glycol oligomers are obtained by anionic polymerization of ethylene oxide. See, for example, G. O. Curme and F. Johnston, Glycols, Reinhold, New York, 1953. They are commercially available (as PEG-200, PEG-400, etc., to indicate the average molecular weight of the major components).

by bis-dinitrophenylation, chromatographic separation, and end-group removal, using high performance liquid chromatography (HPLC) of the bis-(2,4-dinitrophenyl)glycols for purity monitoring. A facile synthetic method for the production of penta-to dodecaglycols in a mixed, aqueous, dioxane solvent system, with fair yields, is also described. The bis-(2,4-dintrophenyl) protection of glycols is a reversible reaction that can be used as (1) a preparative method for pure glycols from readily available commercial polyethylene glycol mixtures; (2) a highly sensitive and accurate analytical method

2 A. Warshawsky, A. Tishbee, and N. Shoef, J. Liq. Chromatogr., submitted for publication.

coupled with HPLC.     

Selective detector of 1,2-propylene glycol dinitrate, 1, propylene glycol mononitrate,and 2-propylene glycol mononitrate using gas chromatography/ thermal energy analyzer or liquid chromatography/ electrochemical detection

Mono- and di-nitrated propylene glycols can be separated and detected using either a gas chromatogph equipped with a nitro-specific thermal energy analyzer (g.c./t.e.a.) or a high-performance liquid chromatograph equipped with an electrochemical detector in the reductive mode (l.c./e.c.). The g.c./t.e.a. exhibits a linear range of three orders of magnitude and provides detection limits in the μg ml^?1 range or lower for these three compounds. The l.c./e.c. provides a linear response over two orders of magnitude and is best suited for the determination of propylene glycol dinitrate. Trapping of these glycols on Amberlite XAD-2 resin is discussed.     

Reactivity of polyesters in glycolysis reactions: Unexpected effect of the chemical structure of the polyester glycolic unit

Kinetic studies of PET glycolysis by diethylene glycol (DEG), dipropylene glycol (DPG), glycerol (Gly) and mixtures of these glycols have shown, in a previous study, that the order of reactivity of the glycols differs according to the conditions of temperature and catalysis. Indeed, their global reactivity depends both on their chemical reactivity and physico-chemical properties.Glycolysis of model polyesters which are liquid at the reaction temperature, which allows us to overcome the problem of the polyesters' solubility, were studied to compare the chemical reactivity of these glycols. Three oligoesters were synthesized from dimethyl terephthalate and three different glycols namely triethylene glycol, ethylene glycol and hexanediol to form, respectively, PE₃T, OET and PTHD.Results showed that the order of reactivity of the glycols is the same for PET, OET and PTHD but different for PE₃T. Indeed, DPG without catalyst has a particular and unexpected behaviour: its reactivity seems to be strongly influenced by the presence of oxygen atoms in the chain.     

Hemichrome Determination by Thermal Lensing with Polyethylene Glycols for Signal Enhancement in Aqueous Solutions

The thermal lens technique is proposed for the determination of total hemoglobin in the form of reversible hemichrome. The conditions were optimized (concentration of sodium dodecyl sulfate, 2?mM) to attain the maximum sensitivity with the use of polyethylene glycols as signal enhancers. For polyethylene glycols with molecular weights 1500–35000 Da in a concentration range of 5–15% w/w (5–25?mM), the influence on thermal lens signal enhancement was estimated. It is shown that the use of 5% w/w polyethylene glycol 2000 provides the maximum increase in the thermal lens enhancement factor (by 40%) in comparison with unmodified aqueous solutions. The detection limit of iron(II) tris(1,10-phenanthrolinate) as a model system is 60?nM. Under these conditions, the thermal lens detection limit of hemichrome is 10?nM, which shows a 15-fold enhancement compared to spectrophotometry. Modification of the medium with polyethylene glycols decreases the limit of detection of hemichrome determination by 15% in comparison with unmodified aqueous solutions due to better reproducibility for the range of concentrations from 0.02 to 0.9?µM.     

New deuterated oligo(ethylene glycol) building blocks and their use in the preparation of surface active lipids possessing labeled hydrophilic tethers

For the introduction of additional analysis protocols of tethered molecules, a method is presented to prepare functionalized, deuterated oligo(ethylene glycols) from ethylene glycol-d4. Partial oligomerization of ethylene glycol-d4 and conversion to ditosylates is accompanied by coupling reactions to prepare doubly benzyl protected oligo(ethylene glycols) with two to five repeating units. The tetramer bearing 16 deuteria was elaborated at both ends to eventually prepare 2,3-di-O-phytanyl-sn-glycerol-1-tetraethylene glycol-d,l-alpha-lipoic acid ester (DPTL), which bears a fully deuterated tetra(ethylene glycol) spacer group. Through linking of functionalized components, an analogue of DPTL possessing an octa(ethylene glycol) spacer group was prepared, both in deuterated and unlabeled form.     

Effect of glycols used as glycolysis agents on chemical structure and thermal stability of the produced glycolysates

In this study, the influence of glycols on chemical structure and thermal stability of glycolysates as polyurethane intermediates were investigated. The intermediates were obtained by the glycolysis process of waste polyurethane foams in the reaction with different glycols ranging from ethylene glycol to hexane-1,6-diol. The used glycols were not separated from the product after the glycolysis process has been terminated. The effects of different weight ratio of glycols to polyurethane (PU) foam on chemical structure and thermal stability were investigated by FTIR, GPC, and TG/DTG. FTIR analysis of the glycolysates revealed their similar chemical architecture as manifested by the similarity of absorption peaks within the entire wavenumber range of spectra. This may indicate that the glycol has no influence on the chemical composition of glycolysates. GPC analysis showed that the glycolysates were characterized by polydispersity smaller than 2 which is lower as compared to some commercial polyols used for PU synthesis. GPC chromatograms showed that the applied glycols and the conditions of PU glycolysis allowed recreation of the original polyol as documented on the chromatograms by a single, well-formed peak at the beginning of retention time. Based on TG thermograms, it was established that glycol used in transesterification of PUs affected the temperature at which the loss of glycolysate mass by 5 and 10?% occurs. It was also observed that glycol affected the temperature at which the decomposition rate of glycolysates was the highest.     

Glass transition temperature of polyurethane foams derived from lignin by controlled reaction rate

Sodium ligninosulfonate (LS)-based polyurethane (PU) foams were prepared using three kinds of ethylene glycols, diethylene glycol, triethylene glycol or polyethylene glycol. Two kinds of industrial NaLS, acid-based and alkaline-based NaLS, were mixed with various ratios, and foaming reactions were controlled. Mixing, cream, and rise time were used as an index of foaming reaction. Mixing time was defined as the time interval from adding isocyanate to detection of evolved heat under stirring, cream time as the time interval from termination of stirring to starting of foaming, and rise time as the time interval from starting to completion of foaming. The above reaction time increased with increasing amount of acid base NaLS content in polyols. Apparent density, compression strength and compression modulus of PU foams linearly increased with reaction time. Thermal decomposition temperature was measured by thermogravimetry and glass transition temperature by differential scanning calorimetry. Glass transition temperature can be controlled in a temperature range from 310 to 390 K by changing the mixing rate of two kinds of LS and molecular mass of ethylene glycols. It was found that mechanical and thermal properties of PU foams are controllable through the foaming reaction rate using two kinds of industrial lignin.     

Recent advances in the bioanalytical methods of polyethylene glycols and PEGylated pharmaceuticals

Polyethylene glycols are synthetic polymers composed of repeating oxyethylene subunits, which have been known for non‐toxic, non‐immunogenic, non‐antigenic, good solubility in water and therefore approved for pharmaceutical applications. Recently, attachment or amalgamation of polyethylene glycols to therapeutic small molecules, peptides, proteins, or nanoparticles has become a mature technology for the sake of improving their pharmacokinetic and pharmacological profiles, also referred to as PEGylation. By comparison, there are only a few PEGylated pharmaceuticals have been registered for further clinical trials and even less was approved for marketing. High failure rate of PEGylated pharmaceuticals in pre‐clinical and clinical trials could be majorly attributed to their unclear pharmacokinetic behaviors. Therefore, the in vivo fate of the PEGylated pharmaceuticals for the various routes of administration needs to be thoroughly investigated An accurate in vivo pharmacological study thereof highly depends on the precise detection of polyethylene glycols as well as their fragments in biological matrixes. The goal of this review is to highlight the analytical methods that were developed and applied to evaluate the polyethylene glycols in pharmaceutical ingredients and excipients, which bring us closer to bridging the gap between the development of polyethylene glycol‐based drug delivery systems and their clinical application.     

Thermophysical characterization of aqueous ternary system containing n-tris-[hydroxymethyl]methyl-3-amino propanesulfonic acid and glycol (PG or DPG or TPG)

In this present work, a thermophysical property characterization of aqueous ternary system containing n-tris-[hydroxymethyl]methyl-3-aminopropanesulfonic acid (TAPS) and glycol was done. Thermophysical properties, including refractive index, density, and electrolytic conductivity, measurements were considered. The glycols considered are propylene glycol (PG), dipropylene glycol (DPG), and tripropylene glycol (TPG). The measurements were done over a temperature range of 298.15 K to 343.15 K and at normal atmospheric pressure. Different concentrations (4% to 16% by weight TAPS or 56% to 44% water, in a fixed amount of glycol – 40%) were used. The effects of temperature and compositions on the measured properties were discussed and then correlated based on the equation proposed for aqueous salt–glycol systems. Calculation results show that the applied model was satisfactory in representing the measured properties in the aqueous ternary systems containing TAPS and considered glycols.     

Thermodynamic Study of Oxyethylated Glycols and Their Mixtures with Tertiary Carboxamides

The contributions into the total energy of intermolecular interactions in oxyethylated ethylene glycol derivatives were estimated in terms of a model approach that uses inner pressure as a measure of nonspecific interactions in a liquid. Increased number of ether groups in ethylene glycols increases the nonspecific contribution and decreases specific contributions. Unlike diethylene glycol, triethylene glycol and tetraethylene glycol contain H-bond networks in the range 298.15–308.15 K. The enthalpies of mixing of tertiary amides with tetraethylene glycol were measured and compared with those for ethylene glycol, diethylene glycol, and triethylene glycol. The effect of the structural and thermodynamic properties of the components on the integral and differential thermochemical characteristics of mixtures of glycols with N,N-disubstituted amides was discussed.     

新型环氧丙烯酸树脂增韧剂的合成

用马来酸酐和聚乙二醇1000合成具有反应活性端基的聚乙二醇,用红外与核磁共振进行了表征,并用其对环氧丙烯酸树脂进行改性;研究反应温度、反应时间对反应及产物性能的影响;用红外对反应性聚乙二醇和环氧丙烯酸树脂的固化物进行分析.结果表明,反应性聚乙二醇参与了环氧丙烯酸树脂的固化反应,可在交联网络中构成不同长度的柔性链段,显著地提高了环氧丙烯酸树脂的冲击强度.     

Model for predicting the composition of copolyesters: Polymerization of terephthalic acid, 2,2′-oxydiethanol,and 2,2-dimethyl-1,3-propanediol

Copolyesters of two glycols and a dicarboxylic acid moiety are frequently made to obtain specific physical properties. In the synthesis of these polymers an excess of glycol is used in the ester-exchange reaction and then removed during the polycondensation reaction to form a high-molecular-weight product. A model has been developed to predict the final polymer composition. The derivation is based on equilibria of reaction species (free glycol, polymer chain ends, and ester links) and the relative vapor pressures of the two reacting glycols. Calculated results are compared with experimental results of poly(2,2′-oxydiethylene: 2,2-dimethyl-1,3-propylene terephthalate)s. There is good agreement between calculated and experimental compositions. The model can be used to calculate the glycol concentrations that must be used to make a specific polymer composition. This model should also be useful in the calculation of other mole ratios of glycol to dicarboxylic acid that will make the same composition.     

Comparative reactivity of glycols in PET glycolysis

The kinetics of poly(ethylene terephthalate) (PET) glycolysis by diethylene glycol (DEG), dipropylene glycol (DPG), glycerol (Gly) and mixtures of these glycols have been studied with two experimental procedures: uncatalysed at 220 °C and catalysed at 190 °C. An experimental device was set up allowing the isothermal kinetics to be monitored. A precise initial reaction time was obtained by separately warming the glycol and the polyester at the temperature of reaction before mixing them.The reactivity order of different glycols varies according to the conditions of temperature and catalysis. Schematically, the global reactivity does depend not only on the chemical reactivity of the glycol but also on its physico-chemical properties: ability to solvate the solid polyesters and polarity of the reaction mixture. Attempts to find synergic effects failed for almost all mixtures, except the mixture DPG + Gly in which the PET is digested more quickly than in pure DPG or Gly.     

A validated GC-MS procedure for fast,simple, and cost-effective quantification of glycols and GHB in human plasma and their identification in urine and plasma developed for emergency toxicology

Methods developed for use in emergency toxicology have to be fast and simple. Additionally, such methods should be multi-analyte procedures because they allow monitoring of analytes of different drug classes in one single body sample. This is important because often only a limited amount of sample is available and the results have to be reported as fast as possible. Therefore, we describe the improvement of an existing method published by van Hee at al. The new method is fast and simple and designed for the simultaneous determination of ethylene glycol, 1,2-propylene glycol, lactic acid, glycolic acid, gamma-hydroxybutyric acid (GHB), diethylene glycol, triethylene glycol, and tetraethylene glycol in human plasma or urine. A 50-μL aliquot of sample was deproteinized and 20 μl of the diluted specimen were derivatized using bis-N,O-trimethylsilyl trifluoroacetamide and the catalyst dimethylformamide. After microwave-assisted derivatization, an aliquot was injected into the gas chromatograph and analyzed with electron ionization mass spectrometry in selective ion monitoring mode. All compounds are separated within 12 min and detected with a limit of quantification of 0.05 and 0.01 g/L for glycols and GHB, respectively. Calibration was linear from 0.05 to 1.0 g/L for glycols and 0.01 to 0.2 g/L for GHB. Validation criteria were shown to be in the required limits with exception of lactic acid. Average analysis time from starting sample preparation until quantitative plasma results of approximately 35 min was achieved. This turnaround time is considered most appropriate for emergency cases.     

Effect of the composition ratio of copolymerized poly(carbonate) glycol on the microphase‐separated structures and mechanical properties of polyurethane elastomers

Randomly copolymerized poly(carbonate) glycols were employed as starting materials for the synthesis of polyurethane elastomers (PUEs). The poly(carbonate) glycols had hexamethylene (C₆) and tetramethylene (C₄) units between carbonate groups in various composition ratios (C₄/C₆ = 0/100, 50/50, 70/30, and 90/10), and the number‐average molecular weights of these poly(carbonate) glycols were 1000 and 2000. The PUEs were synthesized with these poly(carbonate) glycols, 4,4′‐diphenylmethane diisocyanate, and 1,4‐butanediol by a prepolymer method. Differential scanning calorimetry measurements revealed that the difference between the glass‐transition temperature of the soft segment in the PUEs and the glass‐transition temperature of the original glycol polymer decreased and the melting point of the hard‐segment domain increased with an increasing C₄ composition ratio. The microphase separation of the poly(carbonate) glycol‐based PUEs likely became stronger with an increasing C₄ composition ratio. Young's modulus of these PUEs increased with an increasing C₄ composition ratio. This was due to increases in the degree of microphase separation and stiffness of the soft segment with an increase in the C₄ composition ratio. The molecular weight of poly(carbonate) glycol also influenced the microphase‐separated structure and mechanical properties of the PUEs. The addition of different methylene chain units to poly(carbonate) glycol was quite effective in controlling the microphase‐separated structure and mechanical properties of the PUEs. © 2004 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 42: 4448–4458, 2004     

The preparation of macrocyclic polyether-diester compounds by transesterification including the preparation of two new nitrogen containing diester-crown compounds

Macrocyclic polyether-diester compounds have been prepared by reacting oligoethylene glycols with the appropriate dimethyl esters in the presence of catalytic amounts of alkali metal methoxides. The methanol by-product was removed by molecular sieves. Product yields were improved for the preparation of all macrocyclic compounds except a compound containing a furan subcyclic group ( 4 ). Six new macrocyclic diester compounds ( 7-12 ) could only be prepared using the base catalyzed transesterification process since the acid chloride synthetic method failed or the acid chloride could not be made. The formation of compounds 5 and 6 from dimethyl 2, 6-pyridine dicarboxylate ( 17 ) and the triethylene and tetraethylene glycols proceded by way of half-transesterified intermediates. These intermediates were also observed for the base catalyzed decomposition of 5 and 6 in methanol to form the glycol and the diester 17 .     

Separation of polyethylene glycols and maleimide‐terminated polyethylene glycols by reversed‐phase liquid chromatography under critical conditions

The separation of polyethylene glycols and maleimide‐substituted polyethylene glycol derivatives based on the number of maleimide end‐groups under critical liquid chromatography conditions has been investigated on a reversed‐phase column. The critical solvent compositions for nonfunctional polyethylene glycols and bifunctional maleimide‐substituted polyethylene glycols were determined to be identical at about 40% acetonitrile in water on a reversed‐phase octadecyl carbon chain‐bonded silica column using mixtures of acetonitrile and water of varying composition as the mobile phase at 25°C. The maleimide‐functionalized polyethylene glycols were successfully separated according to maleimide functionality (with zero, one, two, or three maleimide end‐groups, respectively) under the critical isocratic elution conditions without obvious effect of molar mass. The separation was mainly due to the hydrophobic interaction between the maleimide end‐groups and the column packing. Off‐line matrix‐assisted laser desorption/ionization time of flight mass spectrometry was used to identify the repeating units and, especially, the end‐groups of the maleimide‐substituted polyethylene glycols. Liquid chromatography analysis at critical conditions could provide useful information to optimize the synthesis of functional polyethylene glycols. To our knowledge, this is the first report of the baseline separation of maleimide‐functionalized polyethylene glycols based on the functionality independent of the molar mass without derivatization by isocratic elution.     

Microscopy and FTIR investigations of the thermal gelation of methylcellulose in glycols

Methylcellulose is a well-known polymer due to its reverse thermal gel formation property in aqueous solutions. Support materials play an important role in the additive manufacturing of three dimensional parts using processes that utilise inkjet technology. This paper presents novel compositions of methylcellulose (MC) in non-aqueous solvents and investigates the thermal gel formation of these compositions. Compositions containing MC in different glycols (ethylene, propylene and butylene glycol) were prepared. Suitability of these compositions as reusable support materials for jetting based three dimensional printing processes have been previously established. In this paper, the mechanism of gelation of MC in three different glycols is explained and compared using experimental techniques such as heating and cooling between 25–150°C, hot stage microscopy and Fourier Transform Infrared (FTIR) spectroscopy. Based on the results, a generalised gel formation diagram for MC in glycols is presented and compared with aqueous MC gel formation. The results showed that MC forms gels in glycols upon cooling and the temperatures of gel formation/melting are different for each glycol. Understanding of the gel formation of these compositions can help in fine tuning these compositions for their performance during three dimensional printing.