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Monitoring of stereoisomer content in samples containing chiral compounds with multiple chiral centers is an important and challenging task in chiral liquid chromatography. 4-Phenyl-5-methylpiracetam, containing two chiral centers, was used as model compound to explore the stereorecognition ability of polysaccharide-based chiral selectors. Initially, the chromatographic behavior of racemic 4-phenyl-5-methylpiracetam on nineteen commercially available polysaccharide-based chiral columns was tested with a mobile phase, consisting of a mixture of ethanol and n-hexane. The obtained results were analysed, and nine chiral phases were selected for further investigation of seven newly synthesized 4-substituted 5-methylpiracetam chiral separations. Our subsequent studies showed that chiral stationary phases based on amylose tris(5-chloro-2-methylphenylcarbamate) and amylose tris[(S)-α-methylbenzylcarbamate] posess higher ability for chiral recognition of stereoisomers of the studied analytes.

This study introduces CADET-Julia, an open-source, versatile and fast chromatography solver implemented in the Julia programming language. The software offers a platform for rapid prototyping and numerical refinement for a range of chromatography models, including the general rate model (GRM). The interstitial column mass balance was spatially discretized using a strong-form discontinuous Galerkin spectral element method (DGSEM) whereas a generalized spatial Galerkin spectral method (GSM) was applied for the particle mass balance. Three different benchmarks showcased the computational efficiency of CADET-Julia: A baseline benchmark was established by comparing the Julia implementation to a C++ implementation that employed the same mathematical methods and time integrator (CADET-DG). Various Julia time integrators were tested, and with the best-performing settings, the Julia implementation was benchmarked against CADET-DG and a finite volume (FV) based implementation in C++ (CADET-FV). Overall, Julia implementations performed better than C++ implementations and Galerkin methods were generally superior to finite volumes. • Free and open-source software in the programming language Julia. • Rapid solution of batch chromatography models. • Utilization of efficient stiff ODE solvers in Julia. • Substantial speedup as compared to C++ implementation. • Platform for rapid prototyping and numerical refinement. [ABSTRACT FROM AUTHOR]

A new selective reverse-phase high-performance liquid chromatography method with an attitude of practical use in pharmaceutical laboratories for simultaneous determination of Ascorbic acid, Acetaminophen, phenylephrine, Caffeine, Pamabrom, Guaifenesin, Dextromethorphan, Pyrilamine, Chlorpheniramine maleate, Ibuprofen in the presence of Methyl, Ethyl, Butyl Parabens as preservatives has been developed and validated. These active pharmaceutical ingredients widely used in a variety of cough and cold medicines. The separation was carried out on an Atlantis dC18 column including 4.6 mm inner diameter, 150 mm length and particle size of 3 μm, using a mobile phase which consisted of an ion-pairing agent (sodium salt of heptane sulphonic acid) as a buffer solution mixed with acetonitrile as an organic modifier at a flow rate of 1 mL min−1 on a gradient system. The investigation was carried out on wavelength program detection to quantify the very low concentration of Dextromethorphan and Chlorpheniramine and high concentration of Acetaminophen, Guaifenesin, Ibuprofen, Ascorbic Acid at the wavelengths of 290 and 215 nm. The temperature was maintained at 40 °C. The method was shown to be linear (R2 > 0.996), accurate (recoveries 97.77–103.94%), precise (RSD ≤ 1.0%), sensitive, specific, simple, fast and robust. The proposed reverse phase-liquid chromatography method was successfully applied to the routine analysis of the Over-The-Counter tablets containing these active pharmaceutical ingredients without any interference with excipients and parabens and 4-aminophenol. [ABSTRACT FROM AUTHOR]

Evaluating lumefantrine enantioselectivity and properly quantifying its enantiomers is essential for a deeper understanding of the impact of the enantioselectivity in the pharmacodynamic and pharmacokinetic properties of the drug. For this, a chiral chromatographic method was developed and validated for the separation of lumefantrine enantiomers. The method developed employed a Chiralpack AD-H column (150 × 4.6 mm, 5 μm), with amylose tris-3,5-dimethylphenylcarbamate stationary phase, at 25 °C, mobile phase composed of hexane and isopropanol (97:3), flow rate of 1.0 mL/min and detection at 335 nm. The method showed adequate resolution for lumefantrine enantiomers and was validated for linearity (48–72 µg/ml for each enantiomer), precision, accuracy, selectivity and robustness. The proposed method was successfully applied for determination of lumefantrine enantiomers in tablet formulations and may be useful to future researchers for chiral evaluation of lumefantrine. [ABSTRACT FROM AUTHOR]

Development of sensitive, acurate, reproducible HPLC-DMD-MS method for determination of the residualamounts of active drug substance "Tryfuzol" in poultryhomogenatesamples and application of this method for testing chiken groups is an important task for the confirmation of thi drug safety. The substance extraction conditions were optimized for methods development. It was established optimum extraction condition. Chromatographic conditions and massspectrometric studies were optimized. As mobilephase, a flowrate of 0.4 ml min-1 isocraticelution 0.1% (v / v) formicacid in water (A) acetonitrile containing 0.1% (v / v) formicacid (B). The composition of the mobile phase of 70% / 30% (v / v). Total running time is 5 minutes. Wave length of the detectoris 276 nm. Control of substances availability was carried by retention time and under UV and massspectra. The technique complies with relevant regulations. The absence of saidsubstance in the study chiken group was proven by using developed techniques.

A sensitive, accurate, precise and rapid HPLC-PDA method was developed and validated for the simultaneous determination of torasemide and spironolactone in human plasma using Design of experiments. Central composite design was used to optimize the method using content of acetonitrile, concentration of buffer and pH of mobile phase as independent variables, while the retention factor of spironolactone, resolution between torasemide and phenobarbitone; and retention time of phenobarbitone were chosen as dependent variables. The chromatographic separation was achieved on phenomenex C18 column and the mobile phase comprising 20 mM potassium dihydrogen ortho phosphate buffer (pH-3.2) and acetonitrile in 82.5:17.5 v/v pumped at a flow rate of 1.0 mL min-1. The method was validated according to USFDA guidelines in terms of selectivity, linearity, accuracy, precision, recovery and stability. The limit of quantitation values were 80 and 50 ng mL-1 for torasemide and spironolactone respectively. Furthermore, the sensitivity and simplicity of the method suggests the validity of method for routine clinical studies

Abstract: In this paper, a thioether-embedded mixed-mode cyano-bonded chromatographic packing has been prepared by using gas silylation method and thiol-ene click chemistry. The solid-state 13C CP/MAS NMR and elemental analysis have been used to characterize the synthesized materials. Detailed chromatographic characterization of the new phase was performed by alkyl benzene homologues in reversed-phase liquid chromatography (RPLC) and was characterized by nucleic acid bases and nucleosides in hydrophilic interaction liquid chromatography (HILIC). The hydrothermal stability has been studied by n-butylbenzene, and results show that the novel cyano-phase had higher stability. In addition, linear solvation energy relationships (LSERs) have been used to investigate the effect of stationary phase property on the retention factor of seven aromatic solutes. The results have shown that the Sil-S-CN phase has a pronounced strong polarity and dipole interactions between stationary phases and analytes.Graphical Abstract: [ABSTRACT FROM AUTHOR]

Abstract: Mono-, di-, and tetramethylglycolurils were synthesized, isolated, and purified. For the first time, the cis- and the trans-isomers of N,N-dimethylglycoluril were isolated as individual substances by semi-preparative HPLC method. The structures of the synthesized compounds were confirmed by 1H NMR, 13C NMR, and HR-HPLC-MS. The EI mass spectra of individual substances were obtained by the GC-MS. Retention and resolution of N-methyl glycolurils were investigated in the reversed-phase HPLC mode for different stationary phases: C18, SB-Aq, and Luna 5u PFP(2). The retention of N-methyl glycolurils depended on the amount of CH3 groups and distance between the CH3 groups in the structure. The stationary phases provided different selectivity for glycoluril and its N-methyl derivatives due to different shape selectivity. Complete separation of the N-methyl derivatives of glycoluril was achieved in 4.5 min on the stationary phase with pentafluorophenyl propyl ligand in a gradient mode.Graphical abstract: [ABSTRACT FROM AUTHOR]

CADET is an open source modeling and simulation framework for column liquid chromatography. The software is freely distributed to both academia and industry under the GPL license ( http://github.com/modsim/cadet ). CADET is based on a core simulator that is written in object oriented C++ and applies modern mathematical algorithms for efficiently solving a variety of customary chromatography models. This simulation engine is interfaced to a suite of MATLAB tools for setting up and executing the most common scientific workflows, e.g., model calibration, process design, robustness analysis, statistical analysis, and experimental design. The model library and numerical methods are continuously extended and improved. For instance, binding models with multiple bound states, pH and/or temperature dependence of binding parameters, surface diffusion, and arbitrary spacing of the radial discretization have been recently added. Moreover, numerical accuracy and computational speed of the code are comprehensively benchmarked using high precision reference solutions and realistic model problems. Versatility of the CADET modeling platform is demonstrated with several examples that are also published as open source code and can be freely adapted to specific use cases. In one of several case studies, sequential and simultaneous optimization of elution gradient shape and cut times are compared for a three component separation. This process is designed to achieve Pareto optimal purity and yield of the central fraction. Moreover, the robustness of these designs with respect to typical process variations is systematically studied. The last case study illustrates the optimal design of experiments for estimating model parameters with maximal accuracy. [ABSTRACT FROM AUTHOR]

A sensitive and accurate LC method for the determination of AT13148 enantiomeric purity has been developed and validated. Baseline separation with a resolution higher than 1.8 was accomplished within 15 min using a Chiralpak AD-H column (250 × 4.6 mm; particle size 5 μm) and n-hexane: 2-propanol: diethylamine (85:15:0.1, v/v) as mobile phase at a flow rate of 1 mL min. Eluted analytes were monitored by UV absorption at 254 nm. The effects of mobile phase components, temperature and flow rate on enantiomeric selectivity and resolution of enantiomers were investigated. Calibration curves were plotted within the concentration range between 7 and 500 μg mL ( n = 11), and the recoveries between 98.24 and 100.99% were obtained, with relative standard deviation lower than 1.32%. LOD and LOQ for AT13148 were 2.46 and 7.38 μg mL and for its enantiomer were 2.54 and 7.49 μg mL, respectively. It was demonstrated that the developed method was accurate, robust and sensitive for the determination of enantiomeric purity of AT13148, especially for the analysis of bulk samples. [ABSTRACT FROM AUTHOR]

In the present work the effects of N -methylation and N -amidination of ampholytic cyclic β -amino acids on their retention and enantioseparation characteristics on Cinchona alkaloid- and sulfonic acid-based zwitterionic chiral selectors, namely Chiralpak ZWIX(+)™ and ZWIX(−)™ columns are described. In a polar-ionic mobile phase, a double ion-pairing interaction mechanism takes place between the charged sites of the chiral analytes (the selectands) and the chiral selector moieties. As a support to correlate the chromatographic results with the structural details of the analytes, pK a values and van der Waals volumes of the substituted amino groups were calculated. In order to ensure better understanding of the mechanistic details of the chromatographic system the composition of the bulk solvent, the role of acid base additives, the concentration of the counter-ions, temperature and the structures of the ampholytic analytes have been investigated. Applying N -Fmoc protection, the ampholytic character of the analytes diminished, leading to a marked loss of retention. In the temperature range studied (5–40 °C) thermodynamic parameters, such as the difference in the standard enthalpy change Δ(ΔH°) , entropy Δ(ΔS) and Gibbs energy Δ(ΔG°) were calculated from linear van’t Hoff plots derived from the ln α vs. 1/T curves. The values of the thermodynamic parameters depended on the structures of the chiral selectors applied and the analytes studied. [ABSTRACT FROM AUTHOR]

Abstract: A quick and reproducible screening analytical method for the simultaneous determination of algal toxins, belonging to different chemical classes, was developed to provide a toxin profile in seawater, useful to assess potential risks to environment and human health. The target compounds were: gonyautoxin-1,4, gonyautoxin-2,3, decarbamoylgonyautoxin-2,3, N‐sulfocarbamoyl-gonyautoxin-1,2, neosaxitoxin, decarbamoyl-neosaxitoxin, saxitoxin, decarbamoyl-saxitoxin, domoic acid, 13-desmethyl spirolide C (SPX1), palytoxin and okadaic acid. Extraction and clean-up were carried out with a combination of Bond Elut LRC-C18 and Carbograph4 cartridges connected in series. Analyte separation was performed in gradient elution mode in 12 min with a Gemini C18 column. Compound detection was carried out in multiple reaction monitoring and in positive ionization mode for paralytic shellfish poisoning toxins, domoic acid, SPX1 and palytoxin, and in negative ionization mode for okadaic acid. The toxins were quantified with matrix-matched calibration curves constructed by spiked seawater samples (concentration levels 0.02–2 μg L−1 depending on the compound). The method was reproducible with intra-day and inter-day relative standard deviations ranging from 4 to 9% and from 8 to 16%, respectively. Good recoveries (84–105%) and good accuracy (2–20%) were obtained by spiking experiments. Limits of detection were calculated for each toxin and varied from 0.011 to 0.12 μg L−1 depending on the compound. The developed method was applied to cultured Ostreopsis cf. ovata samples. The proposed procedure may be considered a valuable alternative to existing methods for monitoring toxic microalgae, since it offers a rapid screening of target toxins, reduced organic solvent consumption, and handling of smaller sample volumes while providing good sensitivity and accuracy.Graphical Abstract: [ABSTRACT FROM AUTHOR]

Packed bed liquid chromatography is widely applied in academia and industry. Model-based methods are increasingly utilized for process development and optimization, demanding multitudes of complex simulations. We derive spatial arbitrary order discontinuous Galerkin (DG) discretizations for three commonly used chromatography models, including the general rate model (GRM). The methods are integrated in the open source CADET software, making efficient implementations publicly available for the first time. The DG CADET code is validated and benchmarked against the original finite volume CADET code. We observe great performance advantages for DG, depending on the discrete problem size. For a four-component steric mass action GRM, we achieve a speed-up of an order of magnitude for an error range typical for engineering applications. We explore the performance of a collocation Legendre–Gauß–Lobatto (LGL) quadrature DG method in comparison to an exact integration DG method. Our performance benchmarks indicate a slight advantage for collocation DG. • CADET is freely available as open source software. • Solver covers a range of reduced order chromatography models. • Fast and accurate high order spatial discretization schemes. • Reduced size of state vector and system Jacobian. [ABSTRACT FROM AUTHOR]

The enantiomers of twelve unusual β2- and β3-homoamino acids containing the same side-chains were separated on chiral stationary phases containing a quinine- or quinidine-based zwitterionic ion-exchanger as chiral selector. The effects of the mobile phase composition, the nature and concentration of the acid and base additives and temperature on the separations were investigated. The changes in standard enthalpy, ∆(∆H°), entropy, ∆(∆S°), and free energy, ∆(∆G°), were calculated from the linear van’t Hoff plots derived from the ln α vs. 1/T curves in the studied temperature range (10–50 °C). The values of the thermodynamic parameters depended on the nature of the selectors, the structures of the analytes, and the positions of the substituents on the analytes. A comparison of the zwitterionic stationary phases revealed that the quinidine-based ZWIX(−)™ column exhibited much better selectivity for both β2- and β3-amino acids than the quinine-based ZWIX(+)™ column, and the separation performances of both the ZWIX(+)™ and ZWIX(−)™ columns were better for β2-amino acids. The elution sequence was determined in some cases and was observed to be R < S and S < R on the ZWIX(+)™ and ZWIX(−)™ columns, respectively.

A novel liquid chromatographic method for the analysis of four potential impurities in the anti-cancer agent Bexarotene has been developed and validated using efficient chromatographic separation, achieved on a C column (50 mm × 2.1 mm, 1.7-μm particles) with a simple isocratic mobile phase at a flow rate of 0.5 mL min. The mobile phase consisted of a 70:30:0.1 (v/v/v) mixture of acetonitrile, water and trifluoroacetic acid, and quantification was achieved by use of ultraviolet detection at 260 nm. Resolution between Bexarotene and its four potential impurities was greater than 2.0. Regression analysis showed the r value (correlation coefficient) was >0.999 for Bexarotene and its four impurities. The method was capable of detecting all four impurities of Bexarotene at levels below 0.10 μg in a Bexarotene test concentration of 0.5 mg mL using an injection volume of 5 μL. The recovery for Bexarotene in assay method at a 100% level was observed to be 99.1 ± 0.32% with % RSD value of 0.5% for drug substance and 98.9 ± 0.46% for Bexarotene capsules with % RSD value of 0.4%. Recovery of imp-1, imp-2, imp-3, and imp-4 from bulk drug samples ranged from 96.3 to 102.0%. Recovery of imp-1, imp-2, imp-3, and imp-4 from Bexarotene Capsule samples ranged from 97.2 to 101.4%. A solution of Bexarotene in ethanol was stable for 48 h. The drug was also subjected to stress conditions as prescribed by ICH Guidelines. Degradation was found to occur under acidic and basic hydrolysis stress conditions; however, the drug was stable to oxidative, photolytic, and thermal stress. Assay of the stressed samples was calculated relative to a qualified reference standard and the mass balance was found to be close to 99.8%. The method was validated for linearity, accuracy, precision, and robustness. [ABSTRACT FROM AUTHOR]

A sensitive and accurate liquid chromatographic method for the determination of AR-42 enantiomeric purity has been developed and validated. Baseline separation with a resolution higher than 1.9 was accomplished within 10 min using a CHIRALPAK AD column (250 mm × 4.6 mm; particle size 5 μm) and n-hexane/2-propanol/diethylamine (75:25:0.1 v/v/v) as mobile phase at a flow rate of 1 mL min. Eluted analytes were monitored by UV absorption at 260 nm. The effects of mobile phase components, temperature and flow rate on enantiomeric selectivity and resolution of enantiomers were investigated. Calibration curves were plotted within the concentration range between 0.001 and 0.5 mg mL ( n = 10), and the recoveries between 98.23 and 101.87% were obtained, with relative standard deviation lower than 1.31%. Limit of detection and limit of quantitation for AR-42 were 0.39 and 1.28 μg mL and for its enantiomer were 0.36 and 1.19 μg mL, respectively. It was demonstrated that the developed method was accurate, robust and sensitive for the determination of enantiomeric purity of AR-42, especially for the analysis of bulk samples. [ABSTRACT FROM AUTHOR]

Mercaptopropyl functionalized polymethylsilsesquioxane microspheres have been prepared by a two-step acid/base catalyzed hydrolysis and co-condensation of methyltrimethoxysilane (MTMS) and mercaptopropyltrimethoxysilane (MpTMS) precursors. The mercaptopropyl loading of the microspheres is controlled by regulating the ratio of MpTMS to MTMS in the reaction feedstock. A pronounced decrease in surface area, pore volume, and pore size with increasing mercaptopropyl loading was observed and a transition in pore structure from mesopores to micropores/nearly nonporous occurred at mole fractions of mercaptopropyl groups greater than 0.23. The resulting particles exhibited low silanol/thiol activity as both the concentrations and dissociation constants of the acidic groups were considerably lower than those reported for inorganic silica-based packings. Chromatographic evaluation using a test mixture containing uracil, toluene, ethylbenzene, quinizarin, and amitriptyline revealed that the new materials possess typical reverse phase chromatographic properties with moderate methylene selectivity and intrinsic inertness to bases. Taken together, the mercaptopropyl functionalized microspheres are a promising alternative to base-deactivated silica-based packings for the separation of the basic compounds which constitute a large proportion of pharmaceuticals. Graphical abstract: [ABSTRACT FROM AUTHOR]

A sensitive and accurate LC method was developed and further validated for the determination of enantiomeric purity of GSK962040. Before separation, a pre-column derivatization procedure was performed. Baseline separation with a resolution higher than 1.9 was accomplished within 15 min using a Chiralpak AD-H (250 × 4.6 mm; particle size 5 μm) column, with n-hexane: 2-propanol (85:15 v/v) as mobile phase at a flow rate of 1 mL min. The eluted analytes were subsequently detected with a UV detector at 260 nm. The effects of mobile phase components and temperature on enantiomeric selectivity as well as resolution of enantiomers were thoroughly investigated. The calibration curves were plotted within the concentration range between 4 and 200 μg mL ( n = 8), and recoveries between 98.15 and 101.48% were obtained, with relative standard deviation (RSD) lower than 1.42%. The LOD and LOQ for the Boc-GSK962040 were 1.23 and 4.15 μg mL and for its enantiomer were 1.38 and 4.76 μg mL, respectively. The developed method was also evaluated and validated by analyzing bulk samples with different enantiomeric ratios of GSK962040. It was demonstrated that the method was accurate, robust and sensitive, and also had practical utilities for real analysis. [ABSTRACT FROM AUTHOR]

A High Performance Liquid Chromatography Mass Spectrometric method for the estimation of Paliperidone in human plasma has been developed and validated using Paliperidone D4 as an internal standard (IS). The extraction of analyte and IS was accomplished by Solid phase Extraction technique. The method has been validated over a concentration range of 0.200 ng/mL to 55.115 ng/mL. Chromatographic separations were achieved using Thermo Betabasic-8, 5 μm 100 mm x 4.6 mm, column eluated at flow rate of 1.0 mL/minute with 1:1 splitted post column with mobile phase Methanol: Ammonium acetate solution (70:30 v/v). The overall run time of method was about 2.8 min. with elution times of paliperidone 1.9 min. The multiple reaction monitoring transitions were set at 427.2 > 207.2 (m/z) and 431.2 > 211.2 (m/z) for paliperidone and paliperidone D4 respectively. The calibration curves were linear (r2≥ 0.99) over the range of 0.200-55.00 ng/mL with lower limit of quantitation validated at 0.200 ng/mL. Extraction recoveries were > 99 % for both paliperidone and its stable labeled IS paliperidone D4. The within run and between run precisions were within 101.5 %, while accuracy ranged from 94.2 to 101.4 %. [ABSTRACT FROM AUTHOR]

A precise and sensitive HPLC method was developed for the determination of p-toluenesulfonoxypropyl-(+)-dihydrotetrabenazine [TsOP-(+)-DTBZ] enantiomeric purity. The effects of mobile phase composition and column temperature on the enantioresolution and analysis time of the enantiomers were investigated. The optimized chiral separation method was performed on a Phenomenex Chirex 3014 column (250 mm × 4.6 mm, particle size 5 μm) using a mobile phase consisting of n-hexane/1,2-dichloroethane/ethanol/trifluoroacetic acid/triethylamine (64/32/4/0.01/0.005 v/v/v/v/v) at a flow rate of 0.8 mL min and a column temperature of 25 °C. The enantiomers were monitored with UV detection at 280 nm, and baseline separation with a resolution higher than 2.0 was achieved within 20 min. The method was validated in terms of linearity, precision, accuracy, robustness, limit of detection (LOD) and limit of quantification (LOQ). The linearity range for the determination of each enantiomer was 0.002-2.0 mg mL ( n = 6). Additionally, the LOD and LOQ of TsOP-(+)-DTBZ were 0.15 and 0.50 μg mL; those for its enantiomer were 0.18 and 0.60 μg mL, respectively. Furthermore, this validated method was successfully applied to analyze three different TsOP-(+)-DTBZ bulk samples. The results demonstrated that the proposed method was simple, rapid, accurate and robust for routine enantiopurity analysis of TsOP-(+)-DTBZ in pharmaceutical research. [ABSTRACT FROM AUTHOR]

The separation ability and retention of normal and reversed phase HPLC with, respectively, three non-polar and two polar mobile phases, have been studied by measuring the retention constants of a series of newly synthesized estrone derivatives. The separation ability and retention are discussed in terms of the nature of the solute, eluent and stationary phase. Good correlation was found between the retention constants log k0 of newly synthesized estrone derivatives obtained on C-18 column and log P calculated by different methods.

In this study, β-cyclodextrin functionalized ionic liquid was prepared by adding 1-benzylimidazole onto 6-monotosyl-6-deoxy-β-cyclodextrin (β-CDOTs) to obtain β-CD-BIMOTs. β-CD-BIMOTs were then bonded onto the modified silica to produce chiral stationary phases (β-CD-BIMOTs-CSP). The performance of β-CD-BIMOTs-CSP was evaluated by observing the enantioseparation of flavonoids. The performance of β-CD-BIMOTs stationary phase was also compared with native β-CD stationary phase. For the selected flavonoids, flavanone and hesperetin obtained a high resolution factor in reverse phase mode. Meanwhile, naringenin and eriodictyol attained partial enantioseparation in polar organic mode. In order to understand the mechanism of separation, the interaction of selected flavonoids and β-CD-BIMOTs was studied using spectroscopic methods (H NMR, NOESY and UV-Vis spectrophotometry). The enantioseparated flavanone and hesperetin were found to form an inclusion complex with β-CD-BIMOTs. However, naringenin and eriodictyol were not enantioseparated due to the formation of hydrogen bonding at exterior torus of β-CD-BIMOTs. [ABSTRACT FROM AUTHOR]

A novel stability-indicating HPLC method was developed and validated for quantitative determination of sotalol-HCl in bulk powder and in tablets. Isocratic HPLC method, using a C18 reversed phase column with mobile phase of 80mM potassium dihydrogen phosphate and acetonitrile (90:10, V/V)was investigated to separate the drug from its stress degradation products. The flow rate was 0.8 mL/min, column oven temperature was ambient and detection was performed at 227 nm. Sotalol-HCl was subjected to the stress conditions of hydrolysis (acid and base), oxidation and photolysis. Stress degraded samples were analyzed by the developed procedure. The analyte was well separated from its degradants. The described method showed excellent linearity over a range of 5-100 μg/mL. The determination coefficient (R2) for sotalol-HCl was 0.9999. Limits of detection and quantification were 1.8 μg/mL and 5 μg/mL, respectively. Degradation of sotalol-HCl was observed in acid and in 30% H2O2 conditions only. The drug was found to be stable in the other stress conditions attempted. The percentage recovery of sotalol-HCl ranged from 98.92 to 99.65% in tablets. The developed method was validated with respect to the linearity, accuracy (recovery), precision, specificity and robustness. The forced degradation studies proved stability indicating power of the method. [ABSTRACT FROM AUTHOR]

A precise and sensitive LC method for the determination of roscovitine enantiomeric purity has been developed and validated. Baseline separation with a resolution higher than 5.8 was accomplished within 15 min using a CHIRALPAK AD column (250 × 4.6 mm; particle size 5 μm) and n-hexane: 2-propanol (80:20 v/v) as mobile phase at a flow rate of 1 mL min. Eluted analytes were monitored by UV detection at 260 nm. The effects of mobile phase components, temperature and flow rate on enantiomeric selectivity and resolution of enantiomers were investigated. Calibration curves were plotted within the concentration range between 0.003 and 1 mg mL ( n = 12), and recoveries between 98.19 and 101.92 % were obtained, with relative standard deviation lower than 1.27 %. LOD and LOQ for roscovitine were 1.15 and 3.85 μg mL and for its enantiomer were 1.07 and 3.42 μg mL, respectively. It was demonstrated that the developed method was accurate, robust and sensitive for the determination of the enantiomeric purity of roscovitine, especially for the analysis of bulk samples. [ABSTRACT FROM AUTHOR]

A poly(ionic liquid-glycidylmethacrylate-co-ethyleneglycol dimethacrylate) monolithic column was prepared via in situ free-radical polymerisation and used as an on-line solid-phase extraction column. The obtained monolithic column was characterized by scanning electron microscopy, Fourier transform infrared spectrometer, nitrogen adsorption-desorption measurement, and mercury intrusion porosimetry, which showed a relatively uniform and porous structure. During the on-line solid-phase extraction-high performance liquid chromatography protocol, nifedipine, nitrendipine, and felodipine were separated efficiently from human plasma using a methanol-water linear gradient at a flow rate of 1.0 mL min. The extraction efficiency for the targets was satisfactory with no matrix interference. Under the optimized extraction conditions, the linear regression coefficient was >0.9973; precisions for inter- and intra-day assays presented as relative standard deviations were less than 7.29 %, and the accuracy and recovery was in the range of 96-105 and 90-106 %, respectively. As a result, the polymerization monolithic column exhibited high selectivity and good permeability, and it was feasible to be used as an on-line SPE column. Meanwhile, validation assays also demonstrated acceptable sensitivity and precision for simultaneous quantitative screening of nifedipine, nitrendipine, and felodipine in human plasma. [ABSTRACT FROM AUTHOR]

The efficiency of numerical methods for solving mass transfer equations, such as in chromatography modeling, crucially depends on the availability of specific derivatives. In particular, vector products with the system Jacobian are frequently required, i.e. derivatives of the right hand side of the spatially discretized partial differential equations with respect to the state variables. More specifically, large systems of non-linear equations are solved in each time step by Newton iterations, typically contributing more than 80% of the total compute time. We apply algorithmic differentiation (AD) combined with block and band compression for efficiently computing the required system Jacobian. Results are compared with a symbolically derived Jacobian based on non-overlapping domain decomposition. The symbolic approach turns out to be roughly two times faster, at the price of rather tedious and error-prone manual derivation of the mathematical equations. AD helps to simplify implementation of the computational code and is much more flexible when model variants are considered. In addition, AD is combined with a forward sensitivity approach for computing parameter sensitivities that are frequently applied in parameter estimation and process optimization. Results are compared with traditional finite differences. Forward sensitivity analysis is more straightforward to apply, as no perturbation factor needs to be chosen, and even computes faster than finite differences for a benchmark example with three chemical components and load, wash and elution phases. [ABSTRACT FROM AUTHOR]

Hydrophobic selectivity is a key factor that has made C-bonded phases the main separation materials for HPLC since its development. However, hydrophobic compounds tend to be strongly retained in these phases meaning that large amounts of organic mobile phases are required. In this work, a new stationary phase was prepared from the immobilization of poly(dimethyl-co-alkylmethylsiloxane) (PDAS) over silica particles using microwave radiation. The optimized conditions for preparation of the stationary phase used 720 W of radiation for 10 min. The chromatographic performance and methylene selectivity in the separation of hydrophobic compounds by this new Si(PDAS) phase were similar to those obtained by typical C-bonded phases. However, the lower hydrophobicity of the organic layer in the Si(PDAS) phase resulted in separation about 40 % faster than typical C phases, requiring more aqueous mobile phases. The Si(PDAS) phase showed lower silanophilic activity than that of typical C phases due to a more effective polymeric coating of the silica surface. [ABSTRACT FROM AUTHOR]

A precise and sensitive LC method for the determination of repertaxin enantiomeric purity has been developed and validated. Baseline separation with a resolution higher than 2.0 was accomplished within 20 min using a Chiralpak AD-H column (250 × 4.6 mm; particle size 5 μm) and n-hexane:2-propanol (90:10 v/v) as mobile phase at a flow rate of 1 mL min. Eluted analytes were monitored by UV detection at 260 nm. The effects of mobile phase composition, temperature and flow rate on enantiomeric selectivity and on resolution of enantiomers were investigated. Calibration curves were plotted within the concentration range between 0.002 and 1.0 mg mL ( n = 3), and relative standard deviation (RSD) of the inter-batch assay and intra-batch assay was less than 1.27 and 1.16 %. LOD and LOQ for repertaxin were 0.65 and 2.19 μg mL; those for its enantiomer were 0.70 and 2.34 μg mL, respectively. The method was evaluated and validated by analysis of bulk samples of repertaxin of different enantiomeric purity. It was demonstrated that the method was accurate, robust, and sensitive, and enabled practical analysis of real samples. [ABSTRACT FROM AUTHOR]

It is a challenge to simultaneously determine the multiple-component targets in complex matrices when some of the targets bear chromophores but some contain no chromophores. A novel HPLC-CAD-DAD method coupled with accelerated solvent extraction and online solid phase extraction (SPE) was developed for simultaneous determination of seven antibiotics in solid bio-matrices. The online SPE operation parameters were optimized on a Acclaim120 C18 cartridge in terms of extraction efficiency with sample injection volume of 1 mL, and the online SPE operation yielded enhancement factors in the range of 29-77 for the different antibiotics. The proposed method showed good recoveries ranging between 79.2 and 104.7 % for different antibiotics and excellent inter-day and intra-day precision with relative standard deviation values ranging from 0.6 to 7.8 %. The detection limits were between 1.8 and 18.0 μg kg. [ABSTRACT FROM AUTHOR]

A precise and sensitive LC method for determination of enantiomeric purity of trelagliptin has been developed and validated. Pre-column derivatization was performed before separation. Baseline separation with a resolution factor >2.5 was accomplished within 10 min by use of a Chiralpak AD column (250 × 4.6 mm; particle size 5 µm) and n-hexane-2-propanol (90:10 v/ v) as mobile phase at a flow rate of 1 mL min. Eluted analytes were monitored by UV detection at 260 nm. The effects of mobile phase composition and temperature on enantiomeric selectivity and on resolution of enantiomers were thoroughly investigated. Calibration curves were plotted within the concentration range 0.005-2 mg mL ( n = 12), and recoveries between 98.23 and 101.34 % were obtained, with relative standard deviation (RSD) <1.39 %. LOD and LOQ for the trelagliptin derivative were 1.51 and 5.03 µg mL; those for its enantiomer were 1.49 and 4.94 µg mL, respectively. The method was evaluated and validated by analysis of bulk samples of trelagliptin of different enantiomeric purity. It was demonstrated that the method was accurate, robust, and sensitive, and enabled practical analysis of real samples. [ABSTRACT FROM AUTHOR]

High-performance liquid chromatographic methods were developed for the separation of enantiomers of four unnatural paclitaxel precursor phenylisoserine analogs on chiral stationary phases containing macrocyclic glycopeptides and cyclofructans as chiral selectors. The effects of the mobile phase composition, the nature and concentration of different mobile phase additives (alcohols, amines and acids) in different chromatographic modes, temperature and the structures of the analytes on the separations were investigated. Separations were carried out at constant mobile phase compositions in the temperature range 10–50 °C on macrocyclic antibiotic-based and 5–35 °C on cyclofructan-based columns and the changes in enthalpy, Δ(Δ H °), entropy, Δ(Δ S °), and free energy, Δ(Δ G °), were calculated. The elution sequence was determined in most cases; no general rule could be observed. [ABSTRACT FROM AUTHOR]

In this paper, a simple, robust and selective liquid chromatographic method was developed and validated for the analysis of warfarin and its process-related impurities. The chromatographic separation was achieved on Phenomenex Gemini C column by employing mobile phase comprising water:acetonitrile:acetic acid-41:59:0.1 % v/v at 1.1 mL min flow rate. Factorial design with multi-criteria decision-making approach was utilized to evaluate the effects of quantitative factors (aqueous content, flow rate and types of acid additive) over selected qualitative responses to achieve a compromise between resolution and analysis time. Finally, the method was validated according to ICH Q2(R1) guidelines and successfully applied for determination of warfarin and its two process-related impurities in commercially available tablets. The robustness of the method was also studied using fractional factorial design and robust domains were established using contour profiling. The proposed method separated warfarin and its related impurities within a short run time of 5 min thereby enabling the developed method cost-effective than the reported methods. [ABSTRACT FROM AUTHOR]

A simple reverse-phase method for the selective quantification of pitavastatin calcium (PIT) and its related substances was developed. The method demonstrated an excellent separation between PIT and each of 15 impurities (including its isomers and degradants) within a short run time of 12 min by HPLC. A rapid resolution similar to that of UHPLC was achieved using high flow rate on superficially porous C18 stationary phase. A synergistic combination of quality by design approach and use of a superficially porous column delivered a HPLC method with ultra-high performance. Forced degradation studies proved the method to be highly specific (mass balance > 98 %) and the structures of major degradation products were proposed based on LC-MS analysis. The results of validation proved the method to be highly precise (%RSD < 4), accurate (recoveries in range of 100 ± 7 %), linear ( r > 0.999) and sensitive (LOQ ≤ 0.02 % and LOD ≤ 0.005 %) for all the impurities and drug. Use of multivariate analysis helped to incorporate high robustness in the method. The method is valuable for quantification of PIT and its related substances in both drug substance and oral solid dosage form. [ABSTRACT FROM AUTHOR]

A simple, rapid, and sensitive high-performance liquid chromatography (HPLC) method was developed and validated for identification and determination of flavonoids inConvolvulus pilosellifolius. The chromatographic separation was achieved in less than 6 min using C18 column (150 × 4.6 mm, 3 μm) with isocratic mixture of methanol and water containing 0.1 percent v/v formic acid in the ration of 80:20 at 258 nm with a flow rate of 0.4 mL/min. The method was validated in the linear calibration curve ranged between 1 and 300 μg/mL with detection limits of 0.39 and 0.26 μg/mL and quantification limits of 1.20 and 0.79 μg/mL for quercetin and kaempferol, respectively. Good repeatability of the method were achieved at percent relative standard deviation (RSD < 2.18 percent) with respect to inter- and intraday repeatability. Recovery values were found to be in the range of 98.2–100.2 percent, indicating high accuracy of the method. The maximum flavonoid contents were 1.07 and 1.54 percent for quercetin and kaempferol, respectively. [ABSTRACT FROM PUBLISHER]

A numerically calculated method was used to study the influence of radial heterogeneity upon columns of different lengths. In this study, we assumed the fourth-order polynomial distribution function of mobile phase flow velocity and the local efficiency. The results relating to column efficiencies and tailing factors show that long and high efficiency columns are influenced by radial heterogeneity more than the shorter and low efficiency columns are influenced. Radial heterogeneity has various effects on columns of different lengths. The results indicate that an extreme high efficiency column has a threshold of length. When the length exceeds the threshold, increasing length will not result in a significant increase in the column plate numbers. The influence of radial heterogeneity upon mobile phase flow velocity and local column efficiency also varies. The radial distribution of local efficiency can enhance the effects of the mobile phase flow velocity radial distribution. [ABSTRACT FROM PUBLISHER]

A new column frit structure termed ring frit was designed in this work to decrease the influence of column radial heterogeneity. Ring frit structure was characterized by a central impervious region which allowed the mobile phase to be injected only through the peripheral region into the column. This design was implemented to reduce the velocity gradient caused by radial heterogeneity and make the flow distribution uniform to improve column efficiency. The contributions of ring frit to column efficiency were confirmed by the computational fluid dynamics method and real life column experiments. Compared with a conventional frit, a ring frit structure can decrease the influence of radial heterogeneity on columns. Moreover, the effects of ring frit structure were related to the diameter of the central impervious region and column length. [ABSTRACT FROM AUTHOR]

A precise and sensitive LC method was developed and further validated for the determination of enantiomeric purity of ( S)- N-[2-(3-{ trans-4-hydroxy-4-[5-(pyrimidin-2-yl)pyridin-2-yl] cyclohexylamino} pyrrolidin-1-yl)-2-oxoethyl]-3-(trifluoromethyl) benzamide (PF-04136309). Baseline separation with a resolution higher than 1.8 was accomplished within 40 min using a CHIRALPAK AD (250 × 4.6 mm; particle size 5 μm) column, with n-hexane:2-propanol (70:30 v/v) as mobile phase at a flow rate of 1 mL min. The eluted analytes were subsequently detected with a UV detector at 260 nm. The effects of mobile phase components and temperature on enantiomeric selectivity as well as the resolution of enantiomers were thoroughly investigated. The calibration curves were plotted within a concentration range between 0.01 and 1 mg mL ( n = 9), and recoveries between 98.17 and 101.28 % were obtained, with relative standard deviation (RSD) lower than 1.44 %. The LOD and LOQ for PF-04136309 were 3.59 and 11.54 μg mL and for its enantiomer were 3.39 and 11.28 μg mL, respectively. The developed method was demonstrated to be accurate, robust and sensitive for the determination of enantiomeric purity of PF-04136309, especially for the analysis of bulk samples. [ABSTRACT FROM AUTHOR]

The enantiomers of four unusual, rather rigid isoxazoline-fused 2-aminocyclopentanecarboxylic acids were directly separated on a quinine- or a quinidine-based zwitterionic ion-exchanger as chiral selector. The effects of the mobile phase composition, the structures of the analytes and temperature on the separations were investigated. Experiments were performed at constant mobile phase composition in the temperature range 10–50 °C to study the effects of temperature, and thermodynamic parameters were calculated from plots of ln α versus 1/ T . Some mechanistic aspects of the chiral recognition process are discussed with respect to the structures of the analytes. It was found that the enantiomer separations were in most cases predominantly enthalpy-driven, but entropically-driven separations were also observed. The sequence of elution of the enantiomers was determined in all cases. [ABSTRACT FROM AUTHOR]

Elution and solvation processes in liquid chromatography may be controlled by temperature changes. In the case of solvent adsorption, the temperature influences the amount of adsorbed solvent as well as the enthalpy and entropy of the solvation process. In this work, the thermodynamic parameters of organic solvents used as organic modifiers in the reversed-phase high-performance liquid chromatography elution process were determined. The changes of enthalpy and entropy in a series of chemically bonded stationary phases were measured to determine the effects of the temperature and surface coverage density of octadecyl ligands on the thermodynamic parameters of the solvation. For both the enthalpy and entropy a parabolic trend was observed with the minimum for medium surface coverage. The correlation of solvent adsorption values with the enthalpy of solvation was also investigated. The highest influence of the temperature on solvation process was observed for stationary phases with high surface coverage. [ABSTRACT FROM AUTHOR]

The enantiomers of twelve unusual β2- and β3-homoamino acids containing the same side-chains were separated on chiral stationary phases containing a quinine- or quinidine-based zwitterionic ion-exchanger as chiral selector. The effects of the mobile phase composition, the nature and concentration of the acid and base additives and temperature on the separations were investigated. The changes in standard enthalpy, Δ(ΔH°), entropy, Δ(ΔS°), and free energy, Δ(ΔG°), were calculated from the linear van’t Hoff plots derived from the ln α vs. 1/T curves in the studied temperature range (10–50 °C). The values of the thermodynamic parameters depended on the nature of the selectors, the structures of the analytes, and the positions of the substituents on the analytes. A comparison of the zwitterionic stationary phases revealed that the quinidine-based ZWIX(−)™ column exhibited much better selectivity for both β2- and β3-amino acids than the quinine-based ZWIX(+)™ column, and the separation performances of both the ZWIX(+)™ and ZWIX(−)™ columns were better for β2-amino acids. The elution sequence was determined in some cases and was observed to be R < S and S < R on the ZWIX(+)™ and ZWIX(−)™ columns, respectively. [ABSTRACT FROM AUTHOR]

A novel hyphenated technique based on ultrasonic-assisted dispersive liquid-liquid microextraction (UA-DLLME) coupled with derivatization has been established for the determination of brassinolide (BL, a representative of brassinosteroids) by HPLC fluorescence detection. 9-Phenanthreneboronic acid is used as labeling reagent of BL. UA-DLLME parameters containing type and volume of extraction and disperser solvent, pH and ultrasonication time are optimized. Derivatization parameters are optimized included amount of 9-phenanthreneboronic acid, volume ratio of pyridine, derivatization time and temperature. Under optimal conditions, quantitative linear range of BL is 50-1,000 ng L and excellent linear response is observed with correlation coefficient of 0.9996. Limit of detection and limit of quantification are calculated as 8.0 and 25.0 ng L, respectively. RSDs of retention time and peak area are in the range of 0.68-0.97 % and 4.61-6.54 % for intra-day precision, 1.32-1.94 % and 7.28-9.75 % for inter-day precision, respectively. Accuracy is satisfactory in the range of 82.3-125.1 %. RSDs' values of repeatability are in the range of 0.82-1.79 and 3.95-8.53 % for retention time and peak area, respectively. Enrichment factor for BL is 189. The results of recovery and matrix effect are in the range of 82.0-108.6 and 90.0-115.3 %, respectively. The proposed method has been applied for the determination of BL in Arabidopsis thaliana, Daucus carota and Brassica campestris L. leaves with much higher sensitivity than many other methods. [ABSTRACT FROM AUTHOR]

A conical microcolumn packed with γ-methacryloxypropyltrimethoxysilane ( γ-MPS)-modified silica particles was developed for the separation/preconcentration of trace carbamazepine, amitriptyline, quetiapine, clozapine, clomipramine, and thioridazine in rat plasma and environmental water samples followed by liquid chromatography method coupled with ultra-violet detector. The chromatographic analysis was performed on a C column under optimal conditions (mobile phase: ammonium acetate (0.03 mol L)-methanol-acetonitrile (37.0:44.1:18.9, v/v/v); flow rate: 1.0 mL min; detection wavelength: 238 nm; column temperature: 25 °C). The prepared γ-MPS-modified silica particles were characterized by Fourier transform infrared spectroscopy and a Varian Infinity-plus400 NMR spectrometer. Various influencing factors such as pH, elution solvent and volume, flow rate and sample volume were investigated systematically. Under the optimal conditions, the method detection limits and the limits of quantitation were 0.7 and 2.1 ng mL for carbamazepine, 0.4 and 1.3 ng mL for amitriptyline, 0.6 and 1.8 ng mL for quetiapine, 0.7 and 2.1 ng mL for clozapine, 1.5 and 4.7 ng mL for clomipramine, 0.8 and 2.6 ng mL for thioridazine, respectively. The relative standard deviations for six replicates of analytes at 0.050 µg mL were less than 4.1 %. The proposed method was applied to the determination of trace amounts of the analytes in the spiked rat plasma and environmental water samples with satisfactory recoveries. It showed wide potential application in the field of the analysis of pharmaceuticals in real environmental water samples and the therapeutic drug monitoring. [ABSTRACT FROM AUTHOR]

Highlights: [•] Simple and rapid vortex-assisted magnetic dispersive solid-phase microextraction. [•] Magnetic dummy imprinted microspheres synthesised by aqueous suspension polymerisation. [•] Selective screening and recognition of dicofol in tea products. [•] Extraction efficiency was markedly increased with reduced equilibrium time. [Copyright &y& Elsevier]

The effects of sample dilution and volume on the peak shapes in hydrophilic interaction liquid chromatography (HILIC) were evaluated using fluorescence-labeled thiols as model compounds and ZIC-HILIC as the HILIC column. The content of acetonitrile, which was selected as the diluent of the aqueous samples in this study, was varied 0−95 % in the injection samples, and the numbers of theoretical plates (NTPs) and retention times were compared using a mobile phase composed of ammonium formate buffer/acetonitrile (25:75, v/v). Although the NTPs and retention times decreased with decreasing acetonitrile content, the peak shapes were acceptable for samples with acetonitrile contents down to 50 % based on asymmetry factor. Furthermore, the sample volume had a serious effect for samples with low acetonitrile contents. Although a high content of acetonitrile in samples is still recommended, the capacity for the aqueous solution in the injection samples under HILIC conditions should vary with the composition of the mobile phase and may be larger than previously thought. These findings should be helpful in deciding the sample composition under HILIC conditions, particularly in bioanalysis, where aqueous solution is often contained in the injection samples and the sample dilution with an organic solvent may decrease the detection sensitivity. [ABSTRACT FROM AUTHOR]

Stability-indicating LC methods were developed and validated for the quantitative determination of doripenem, meropenem and tebipenem in the presence of their degradation products formed during forced degradation studies. Isocratic HPLC and UHPLC separations were performed with a core-shell Kinetex 1.7, 2.6 and 5 µm, all C18, 100A, 100 × 2.1 mm columns and the mobile phase composed of acetonitrile and 12 mmol L ammonium acetate in different ratios. The flow rates of the mobile phase were: 0.5 mL min for 1.7 µm column, and 1.0 mL min for 2.6 and 5 µm ones. Detection wavelength was 298 nm and temperature was set at 30 °C. All analysed drugs were exposed to stress conditions which caused their hydrolysis and thermal degradation. The methods were validated by evaluation of linearity, accuracy, precision, selectivity and robustness. Proposed methods were successfully applied for the determination of investigated antibiotics during kinetic studies in aqueous solutions and in the solid state. The advantages of chromatographic procedures which are based on the use of C18 stationary phases with different particle sizes in the analysis of selected carbapenems were discussed. [ABSTRACT FROM AUTHOR]

A sensitive UHPLC-DAD method was developed for determination of diastereoisomers of cefuroxime axetil in bulk substance in amorphous and crystalline forms as well as in pharmaceutical preparations. Chromatographic separation was achieved on Kinetex C-18 (100 mm × 2.1 mm, 1.7 µm) column with mobile phase consisting of 0.1 % formic acid:methanol (88:12, v/v), at the flow rate of 0.7 mL min and total run time of 3 min. The wavelength of the DAD detector was set at 278 nm. Inter-day precision (RSD) was less than 3 % and accuracy level ranged between 98.31 and 104.99 %. Degradation products of cefuroxime axetil in aqueous solutions and in the solid state were identified with a EIS-Q-MS mass spectrometer. The solubility of above-mentioned polymorphic forms of cefuroxime axetil in suitable solvents is a crucial factor during preparation of samples and is essential for chromatographic separation of its diastereoisomers. [ABSTRACT FROM AUTHOR]

Two chiral stationary phases containing a quinine- or a quinidine-based zwitterionic ion-exchanger as chiral selector were applied for the enantioseparation of 27 unusual cyclic secondary α-amino acids. The effects of the nature and concentration of the bulk solvent, the acid and base additives, the structures of the analytes and temperature on the enantioresolution were investigated. To study the effects of temperature and to obtain thermodynamic parameters, experiments were carried out at constant mobile phase compositions in the temperature range −5 to 55 °C. The thermodynamic parameters indicated that in most cases the separations were enthalpy-driven, but some entropy-driven separations were also observed. The sequence of elution of the enantiomers was determined in most cases. [ABSTRACT FROM AUTHOR]