Standard Stationary Phase Research Articles

A general procedure for finding potentially erroneous entries in the database of retention indices

BackgroundThe NIST retention index database is one the most widely used sources of retention indices. In both untargeted analysis and machine learning studies filtering for potential errors is rather lacking or nonexistent. According to our estimates about 80% of the compounds from both NIST 17 and NIST 20 retention index databases have only one RI value per stationary phase, which makes searching for erroneous values with statistical methods impossible. Manual inspection is also impractical because the database contains more than 300 000 entries. ResultsWe suggest a two-step procedure to find potentially erroneous retention indices based on machine learning. The first step is to use five predictive models to obtain predicted retention index values for the whole database. The second one is to compare these predicted values against the experimental ones. We consider a retention index erroneous if its accuracy (the difference between predicted and experimental value) is in the bottom 5% for each of the five models simultaneously. Using this method, we were able to detect 2093 outlier entries for standard and semi-standard non-polar stationary phases in the NIST 17 retention index database, 566 of those were corrected or removed by the developers in the NIST 20. SignificanceThis is a novel approach to find potentially erroneous entries in a large-scale database with mostly unique entries, which can be applied not only to retention indices. The procedure can help filter and report mishandled data to improve the quality of the dataset for machine learning applications and experimental use.

Eccentric catastrophes & what to do with them

Analytic modeling of gravitational waves (GWs) from inspiraling eccentric binaries poses an interesting mathematical challenge. When constructing analytic waveforms in the frequency domain, one has to contend with the fact that the phase of the Fourier integral in non-monotonic, resulting in a breakdown of the standard stationary phase approximation (SPA). In this work, we study this breakdown within the context of catastrophe theory. We find that the SPA holds in the context of eccentric Keplerian orbits when the Fourier frequency satisfies , where are integer multiples of the apocenter/pericenter frequencies, respectively. For values outside of this interval, the phase undergoes a fold catastrophe, giving rise to an Airy function approximation of the Fourier integral. Using these two different approximations, we generate a matched asymptotic expansion that approximates generic Fourier integrals of Keplerian motion for bound orbits across all frequency values. This asymptotic expansion is purely analytic and closed-form. We discuss several applications of this investigation and the resulting approximation, specifically: (1) the development and improvement of effective fly-by waveforms for binary black holes, (2) the transition from burst emission in the high eccentricity limit to wave-like emission in the quasi-circular limit, which results in an analogy between eccentric GW bursts and Bose–Einstein condensates, and (3) the calculation of f-mode amplitudes in eccentric binary neutron stars and black hole-neutron star binaries in terms of complex Hansen coefficients. The techniques and approximations developed herein are generic, and will be useful for future studies of GWs from eccentric binaries within the context of post-Newtonian theory.

Selectivity comparison of acetonitrile-methanol-water ternary mobile phases on an octadecylsiloxane-bonded silica stationary phase.

The solvation parameter model was used in this study to investigate various intermolecular interactions that influence retention on the standard C18 stationary phase for the solvent system acetonitrile:methanol (ACN:MeOH, 1:1). In comparison to the organic mobile phase modifiers acetonitrile, acetone, methanol, 2-propanol, and tetrahydrofuran, the solvent strength for the ACN:MeOH (1:1) solvent system was evaluated. To facilitate the interpretation of various intermolecular interactions that contribute to retention on a standard C18 stationary phase for the solvent system ACN:MeOH (1:1), system maps were constructed and compared with those of acetone, tetrahydrofuran, acetonitrile, 2-propanol, and methanol. The solvation parameter models were constructed for the ternary solvent system ACN:MeOH (1:1)-water, and in the models constructed, the coefficient of determination values were from 0.998 to 0.999, the Fisher statistic values for the models were from 1687 to 4015, and the standard error of the estimate values ranged from 0.022 to 0.029. The solvent system ACN:MeOH (1:1) has retention properties more similar to methanol than acetonitrile, indicating methanol's influence is more dominant.

Simultaneous assessment of atorvastatin-ezetimibe combination in tablets by an ion-pair rp-hplc

The purpose of this work was to develop and validate a new ion-pair reversed phase high performance liquid chromatographic method on a standard C18-type stationary phase with UV detection, for the analysis of the two antihyperlipidemic agents as a combination in tablets atorvastatin-ezetimibe. The mobile phase consisted of a 35% of cetyltrimethylammonium bromide (cetrimide) 10−3 M as the ion-pairing agent and 65% acetonitrile. The pH value of the mobile phase was adjusted if necessarily by ammonia solution at 10. The flow rate was 1.5 mL/min and the separation was performed at 40°. The method validation was based on linearity, accuracy, precision and specificity. This method exhibited good linearity and accuracy with mean recovery values between 95–105%, precision with relative standard deviations of the calculated concentrations less than 2% and specificity in the presence of excipients. These results indicates that the proposed method is applicable for the separation and determination of atorvastatin-ezetimibe combination in tablets and could be a relevant method to utilize in quality control laboratories.

Gas Chromatographic Retention Index Prediction Using Multimodal Machine Learning

Gas chromatography is a widely used method in analytical chemistry and metabolomics. Using gas chromatography, vaporizable compounds can be separated for their further identification. Retention indices are standardized values that depend only on a chemical structure of a compound and on a stationary phase and characterize the retention of a compound in a chromatographic system. Retention index prediction is an important task because databases contain experimental values for a small fraction of all possible molecules, while this information is usable for untargeted analysis. In this work, we consider four machine learning models for retention index prediction: 1D and 2D convolutional neural networks, deep residual multilayer perceptron, and gradient boosting. String representation of the molecule, 2D representation of the chemical structure, molecular descriptors and fingerprints, and molecular descriptors are used as inputs of these four models, respectively, along with information about the stationary phase. The first and third models show the best performance, while the other two perform slightly worse. The models predict retention index values for various standard and semi-standard non-polar stationary phases. Further improvement in performance was achieved using a linear model that uses the results of four previous models as inputs (model stacking). The models were tested using various diverse data sets: flavor compounds, essential oils, metabolomics-related compounds. Achieved accuracy: median absolute and percentage errors – 6–40 units and 0.8-2.2%. Accuracy depends on a test data set. The stacking model outperforms previously reported approaches for all test data sets. Parameters of a pre-trained model and some source code are provided.

Identification features of volatile impurities in ethyl alcohol using gas chromatographic retention indices

The restrictions of the commonly used determination algorithm of gas chro­matographic retention indices ( RI ) for the volatile impurities identification of ethyl alcohol being eluted prior to the principal constituent on the standard polar stationary phases (polyethylene glycols) are confirmed. The main reason of the­se restrictions seems to be the interfering n -alkanes С 6 – С 9 reference with the most of impurities. Due to this reason the identification of ethanol impurities to date preferably is based on comparing the profiles of chromatograms of target samples and those of model mixtures. It is shown that RI calculation in similar cases can be based on the data for the non-alkane reference constituents with known RI values that are always contained in the samples, namely acetone (RI 819 ± 6) and methanol (819 ± 6), in combination with the hold-up time value. Just the RI calculation permits us to reveal few groups of difficult to separate constituents as well as to identify some constituents previously not mentioned among ethanol impurities such as formaldehyde diethyl acetal (RI 860 ± 7) and ethyl vinyl ether (667 ± 10). The identification of ethyl vinyl ether is also confirmed by the analysis of the sample enriched with this ether in the result of the treatment of ethanol, containing small amounts of water, by calci­um carbide. In addition, the presence of ethyl vinyl ether is suggested in the sample of absolute ethanol prepared according to the known laboratory method by boiling with anhydrous cal­cium oxide. The evaluation of quantitative content of impurities is fulfilled using the internal standard method with acetone and methanol as standards. Keywords: Ethyl alcohol, impurities, gas chromatographic analysis, identification, vinyl ethyl ether, formaldehyde diethyl acetal (Russian) DOI: http://dx.doi.org/10.15826/analitika.2019.23.4.013 1 Alena I. Desyatova, 2 Nina G. Kovaleva, 3 Dmitrii A. Ponomarev, 1 Igor G. Zenkevich 1 St. Petersburg State University, Institute for Chemistry, Universitetskii prosp., 26, St. Petersburg 198504, Russian Federation 2 «Ekroskhim», Evpatoriiskii by-str., 7A, St. Petersburg 194044, Russia т Federation 3 St. Petersburg State Forest Technical University, Institutskii by-str., 5, St. Petersburg 194021, Russian Federation

Characterization of Dialkyl Phosphites by Gas Chromatography–Mass Spectrometry

The homologous series of dialkyl phosphonates (CnH2n + 1O)2PH=O] (2 ≤ n ≤ 9) (dialkyl phosphites is their commonly used trivial name) was characterized by electron ionization mass spectra and retention indices (RIs) on an RTX-5 standard nonpolar stationary phase. It was established that, in the presence of even one chiral center in the alkyl fragments (for example, in sec-alkanol esters), dialkyl phosphonates were detected in the form of several chromatographic signals due to diastereomers with differences in the retention indices from 4 to 21. The four-coordinated phosphorus atom is the second chiral center. The homologous increments of the retention indices of di-n-alkyl phosphonates (iRI ± sRI = 29 ± 9) and esters having one (–4 ± 10) and two (–61 ± 14) branching points in the carbon skeletons of alkyl fragments were evaluated. These values, which were calculated based on data for a limited number of homologues, make it possible to characterize any compounds from the test series. It was found that the relationship М ≈ 0.14(RI – iRI) + y makes it possible to uniquely determine the molecular weights of analytes according to chromatographic data under the condition of rounding the results to the nearest value of M comparable with y = 12 to the modulus 14 [М ≡ 12(mod14)].

Back-propagation imaging by exploiting multipath from point scatterers

An inverse scattering problem under the linearised Born approximation is considered for a non-homogeneous background medium. An ensemble of pointlike scatterers is oppositely deployed in the scattering scene in order to introduce multipath and to gain an advantage in the reconstruction procedure. It is well known that inverse scattering can benefit from multipath, but at the same time it can produce artefacts in the reconstructions. This is confirmed once again in this study. Indeed, we show that some artefacts, which have been discarded in some previous works, are actually the cause of resolution improvement. To this end, standard stationary phase arguments are employed along with an adjoint inversion method (backpropagation). Theoretical results succeeds in predicting the reconstruction’s leading order terms. However, spurious artefacts due to high order terms become relevant, because more than one point scatterer is used. A simple way to mitigate such artefacts without renouncing the gain in resolution is introduced for the case where the unknown scatterers are small compared to the wavelength.

Special features of gas chromatography determination of dibenzyl ether hydroperoxide impurity in benzyl alcohol

Chromato–mass spectrometric analysis of a benzyl alcohol sample has revealed the presence of dibenzyl ether hydroperoxide C6H5CH(OOH)OCH2C6H5 impurity showing the retention index 1894±10 on a standard stationary phase (RTX-5). A special feature of this hydroperoxide is its stability under conditions of gas chromatography separation (retention temperature 190°С). This has been confirmed by the measurement of the analytical signal between the chromatographic peaks of the hydroperoxide and the major product of its decomposition (benzyl benzoate). From this criterion, dibenzyl ether hydroperoxide is more stable that, for instance, monomethyl phthalate.

Generalized stationary phase approximations for mountain waves

Large altitude asymptotic approximations are derived for vertical displacements due to mountain waves generated by hydrostatic wind flow over arbitrary topography. This leads to new asymptotic analytic expressions for wave-induced vertical displacement for mountains with an elliptical Gaussian shape and with the major axis oriented at any angle relative to the background wind. The motivation is to understand local maxima in vertical displacement amplitude at a given height for elliptical mountains aligned at oblique angles to the wind direction, as identified in Eckermann et al. [“Effects of horizontal geometrical spreading on the parameterization of orographic gravity-wave drag. Part 1: Numerical transform solutions,” J. Atmos. Sci. 72, 2330–2347 (2015)]. The standard stationary phase method reproduces one type of local amplitude maximum that migrates downwind with increasing altitude. Another type of local amplitude maximum stays close to the vertical axis over the center of the mountain, and a new generalized stationary phase method is developed to describe this other type of local amplitude maximum and the horizontal variation of wave-induced vertical displacement near the vertical axis of the mountain in the large altitude limit. The new generalized stationary phase method describes the asymptotic behavior of integrals where the asymptotic parameter is raised to two different powers (1/2 and 1) rather than just one power as in the standard stationary phase method. The vertical displacement formulas are initially derived assuming a uniform background wind but are extended to accommodate both vertical shear with a fixed wind direction and vertical variations in the buoyancy frequency.

“Measure Your Gradient”: A new way to measure gradients in high performance liquid chromatography by mass spectrometric or absorbance detection

The gradient produced by an HPLC is never the same as the one it is programmed to produce, but non-idealities in the gradient can be taken into account if they are measured. Such measurements are routine, yet only one general approach has been described to make them: both HPLC solvents are replaced with water, solvent B is spiked with 0.1% acetone, and the gradient is measured by UV absorbance. Despite the widespread use of this procedure, we found a number of problems and complications with it, mostly stemming from the fact that it measures the gradient under abnormal conditions (e.g. both solvents are water). It is also generally not amenable to MS detection, leaving those with only an MS detector no way to accurately measure their gradients. We describe a new approach called “Measure Your Gradient” that potentially solves these problems. One runs a test mixture containing 20 standards on a standard stationary phase and enters their gradient retention times into open-source software available at www.measureyourgradient.org. The software uses the retention times to back-calculate the gradient that was truly produced by the HPLC. Here we present a preliminary investigation of the new approach. We found that gradients measured this way are comparable to those measured by a more accurate, albeit impractical, version of the conventional approach. The new procedure worked with different gradients, flow rates, column lengths, inner diameters, on two different HPLCs, and with six different batches of the standard stationary phase.

Features of the chromatography-mass spectrometric identification of condensation products of the carbonyl compounds

By the example of the condensation products of acetone with the simplest aromatic carbonyl compounds it was shown that the joint interpretation of mass spectrometric and chromatographic data in conjunction with a priori assumptions about the nature of the chemical structure allows the detection of the components of reaction mixtures that were not previously characterized by standard mass spectra or by retention indices on standard stationary phases. A necessary condition for solving such problems is creating a hypothesis about the sample composition that is possible for the expected products of the known organic reactions.

Problems Associated with the Chromatographic Determination of Chlorobenzylgermanium Derivatives Using an Octadecyl Stationary Phase

Results of investigations regarding the difficulties of benzylgermanium determination by high performance liquid chromatography using standard octadecyl stationary phases have been substantiated on the molecular level. The analyzed organogermanium compounds are biologically active and some are used in oncology. Investigations showed modifications of the octadecyl stationary phase caused by the above-mentioned derivatives. These modifications have been confirmed by infrared spectroscopy with Fourier transform (FTIR), 13C CP/MAS Nuclear Magnetic Resonance techniques (NMR), 29Si CP/MAS NMR, and scanning microscopy. The strongest bonds are formed by benzyltrichlorogermanium but the tribenzyl derivative with a sterically large group and the long, 18-carbon chains, is bound only weakly. It also interacts to the smallest extent with residual silanols of the octadecyl phase. Mass ratio germanium to silica calculated on the base of scanning display after modification was 12.63% for monobenzyl derivative, 12.49%, for dibenzyl, and 5.6% for tribenzyl.

Capillary liquid chromatography and capillary electrochromatography using silica hydride stationary phases

A hydride-based octadecyl stationary phase on both 4.0 and 1.8 μm silica particles is tested in both the capillary LC and the pressurized capillary electrochromatography (pCEC) modes. These two materials are compared to standard C18 stationary phase made by organosilanization and to the hydride material packed into a convention 4.6 mm I.D. column. The performance of the capillary columns is evaluated in terms of analysis times for various mixtures as well as efficiency. Of particular interest are the differences between the LC mode where only laminar flow is present and pCEC operation where a flat electrodriven flow profile is superimposed on the parabolic pressurized flow. Differences in performance between columns packed with 4.0 and 1.8 μm particle silica are also evaluated.

A LC-Electrospray Tandem MS Method for the Analysis of Naltrexone in Canine Plasma Employing a Molecular Model to Demonstrate the Absence of Internal Standard Deuterium Isotope Effects

A simple and sensitive method is described for the determination of naltrexone (NAL), an opioid antagonist, in dog plasma. Sample processing involved a single step liquid-liquid extraction, followed by evaporation of the supernatant, and reconstitution of the residue prior to injection into the liquid chromatograph. The peak height ratio of NAL to [15,15,16-(2)H] naltrexone (NAL-d(3)) was used for quantitation. Observation of the chromatograms for NAL and NAL-d(3) revealed that the mean retention times of the compounds were 1.32 and 1.31 min, respectively. The almost identical retention times possibly accounted for the absence of matrix effects influencing quantitation. Molecular mechanics calculations using SYBYL software were carried out to qualitatively and quantitatively assess analyte and isotopic internal standard stationary phase interactions. Binding energy values of -10.22 and -10.26 kcal/mole were obtained for NAL and NAL-d(3), respectively. These data predict, semi-quantitatively, the absence of deuterium isotope effects that may influence quantitation. Calibration curves were linear from 10 pg/mL to 5014 pg/mL with a weighting factor of 1/x. Precision and accuracy and reverse predicted concentration residuals were within 15%. The method has been used successfully for the analysis of plasma samples from a pilot subcutaneous implantation study in dog.

Wrong gas/liquid partition data by gas chromatography

In a paper published in 1992 [K.S. Reddy, J.-Cl. Dutoit, E.sz. Kováts, Pair-wise interactions by gas chromatography. I. Interaction free enthalpies of solutes with non-associated primary alcohol groups, J. Chromatogr. 609 (1992) 229] retention indices and standard chemical potential differences (SPOT-s) are given for about 160 solutes on a liquid branched paraffin hydrocarbon of the carbon number, z = 78. For the temperature dependence of the SPOT-s the proposal of Kirchhoff was accepted i.e. that at higher temperatures the molar heat capacity difference of the solute between the gas phase and the solution is nearly constant in a broad temperature range. The data were determined under conditions where the effect of adsorption could be neglected. By comparing the published data with those determined on another branched paraffin of the carbon number, z = 87 [F. Riedo, D. Fritz, G. Tarján, E.sz. Kováts, A tailor-made C87 hydrocarbon as a possible non-polar standard stationary phase for gas chromatography, J. Chromatogr. 126 (1976) 63] it is shown that the reported thermodynamic constants of solutes determined experimentally at higher temperatures (the group “H”) are wrong on C78. In the present paper, the method of correction and the resulting corrected data are given. In later papers retention data are given on eight polar derivatives of the hydrocarbon C78 relative to those measured on the nonpolar standard [R. Cloux, G. Défayes, K. Fóti, J.-Cl. Dutoit, E.sz. Kováts, Pair-wise interactions by gas chromatography. III. Synthesis of isosteric stationary phases for gas chromatography, Synthesis (1993) 909; G. Défayes, K.S. Reddy, A. Dallos, E.sz. Kováts, Pair-wise interactions by gas chromatography. V. Interaction free enthalpies of solutes with primary chloro- and bromo-alkanes, J. Chromatogr. A 699 (1995) 131; K.S. Reddy, E.sz. Kováts, Pair-wise interactions by gas chromatography. II. Sociation free enthalpies of some hydrogen bonding solutes with non-associated primary alcohol groups, Chromatographia 34 (1992) 249; K.S. Reddy, R. Cloux, E.sz. Kováts, Pair-wise interactions by gas chromatography. IV. Interaction free enthalpies of solutes with trifluoromethyl-substituted alkanes, J. Chromatogr. A 673 (1994) 181; K.S. Reddy, R. Cloux, E.sz. Kováts, Pair-wise interactions by gas chromatography. VI. Interaction free enthalpies of solutes with primary methoxyalkane, cyanoalkane and alkanethiol groups, J. Chromatogr. A 704 (1995) 387; A. Dallos, A. Sisak, Z. Kulcsár, E.sz. Kováts, Pair-wise interactions by gas chromatography. VII. Interaction free enthalpies of solutes with secondary alcohol groups, J. Chromatogr. A 904 (2000) 211]. Obviously, the same data which are wrong in the nonpolar standard are also wrong in these solvents. The corrected data in the polar solvents are given in supplementary tables.

Stationary phase evaluations of quantum rate constants

We compute the quantum rate constant based on two extended stationary phase approximations to the imaginary-time formulation of the quantum rate theory. The optimized stationary phase approximation to the imaginary-time flux-flux correlation function employs the optimized quadratic reference system to overcome the inaccuracy of the quadratic expansion in the standard stationary phase approximation, and yields favorable agreements with instanton results for both adiabatic and nonadiabatic processes in dissipative and nondissipative systems. The integrated stationary phase approximation to the two-dimensional barrier free energy is particularly useful for adiabatic processes and demonstrates consistent results with the imaginary-time flux-flux correlation function approach. Our stationary phase methods do not require calculation of tunneling paths or stability matrices, and work equally well in the high-temperature and the low-temperature regimes. The numerical results suggest their general applicability for calibration of imaginary-time methods and for the calculation of quantum rate constants in systems with a large number of degrees of freedom.

Investigations of a new field in gas chromatography: Capillary columns with a super-thick layer of stationary liquid phase

Basic characteristics (efficiency, selectivity, non-equilibrium) of capillary columns with a super-thick layer of stationary liquid phase are investigated. In contrast to traditionally used capillary columns with standard stationary phase thickness of 0.1–0.5 um, some new variables are now established. Firstly, the values of relative retention depend on carrier gas linear velocity. Secondly, the asymmetry of chromatographic peaks increased in accordance with the increase in carrier gas velocity. Thirdly, it was theoretically and experimentally shown that dependence of the height equivalent to a theoretical plate (HETP) on carrier gas velocity is linear. The above noted variables are evidences that the new type of GC is realized under these conditions. The use of capillary columns with super-thick layer of stationary liquid phase is practical when the following problems have to be solved: (1) Separation of highly volatile substances; (2) Preliminary concentration of trace compounds from strong diluted samples; (3) Improvements in measurement and accuracy due to the advantages of splitless injection into wide bore columns with super-thick films. Solutions to some analytical tasks while using super-thick stationary liquid phase are shown: (1) Large volume injection into capillary column with sample transfer speed up to 100 μL min −1; (2) Isothermal splitless injection; (3) Separation of low boiling compounds; (4) Separation of polar substances (alcohols).

Micro Parallel Liquid Chromatography for High-Throughput Compound Purity Analysis and Early ADMET Profiling

The Nanostream (Pasadena, CA) Veloce system, together with 24-column Brio cartridges, offers a novel approach to micro parallel liquid chromatography (μPLC). This system allows users to achieve unprecedented throughput for standard assays while matching the performance of conventional LC instrumentation, thus enabling routine compound purity assessment and physiochemical property profiling early in the drug discovery and development process. The Veloce system—which includes instrumentation, software, and replaceable microfluidic cartridges—incorporates pressure-driven flow to achieve chromatograms comparable to conventional high performance liquid chromatography (HPLC) instrumentation for a broad class of analytical applications while offering a dramatic increase in sample analysis capacity. The system enables parallel chromatographic separations and simultaneous, real-time UV detection. Each Nanostream Brio cartridge, made of polymeric materials, incorporates 24 columns packed with standard (C-18) stationary phase material to achieve reverse phase separations. Mixing and distribution of the mobile phase to each of the 24 columns is precisely controlled in each cartridge. The system provides an ideal platform to accelerate assessment of compound purity and physicochemical properties (i.e., log P, CHI, etc.) for a large number of compounds. In addition, the 24-fold increase in sample analysis capacity allows standard curve generation and simultaneous analysis of multiple replicates of samples in a single run. (JALA 2004;9:185-91)

Quantitative structure–retention relationships XIV: Prediction of gas chromatographic retention indices for saturated O-, N-, and S-heterocyclic compounds

In this study, quantitative structure–retention relationship (QSRR) technique was used to find the best approximation and to predict gas chromatographic retention indices for O-, N-, and S-heterocyclic compounds on standard nonpolar polydimethyl siloxane stationary phase. Boiling point (BP) and calculated properties were used to encode the structure of compounds. Three- and two-dimensional calculated properties such as weighted–holistic invariant molecular (WHIM) descriptors, geometry topology and atom weights assembly (GETAWAY) descriptors, connectivity indices, and zero-dimensional constitutive descriptors were used. Variable subset selection (VSS) and partial least squares (PLS) projections to latent structures were used to select the most significant variables from a large set of descriptors. Multiple linear regression (MLR) and PLS were applied to find the relationship between selected properties and gas chromatographic retention indices. PLS was not able to select the most important descriptors (boiling point or molecular weight). The predictive ability of the models was tested by cross-validation. Solely calculated descriptors were not able to give proper models. Boiling point was always necessary for good prediction. PLS models containing boiling points were suitable for retention index prediction, whereas MLR did not give real linear models.