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In this study, a discontinuous Galerkin (DG) finite element method is employed to solve the nonlinear equilibrium dispersive (ED) model, for the simulation of multi-component gradient elution chromatography using a liquid mobile phase in fixed-bed columns. The ED model comprises a set of coupled nonlinear convection-dominated partial differential equations integrated with nonlinear Langmuir type adsorption isotherms. Gradient elution, characterized by the gradual increase in eluent strength through variations in the chemical composition of the mobile phase, is analyzed. An investigation into the advantages of gradient elution chromatography in comparison to isocratic elution is conducted via a sequence of numerical test experiments that assess the influence of solvent strength, modulator concentration, gradient start and end times, and gradient slope on the elution profiles and temporal moments. It has been observed that gradient elution chromatography influences the behavior, shape, and propagation speed of elution profiles, which subsequently affect the cycle time and column efficiency. The results of this study provide significant insights that are critical for understanding, optimizing, and enhancing gradient elution chromatography. [ABSTRACT FROM AUTHOR]

Objective To establish a method for the simultaneous determination of DOX·HCl and LND. Methods HPLC was performed on Agilent 5 HC-C18 (2）(4.6 mm × 250 mm, 5 µm) column. The mobile phase was methanol-0.1% TFA aqueous solution, and the gradient elution procedure were: 0 to 3 min, 65% methanol; 3 to 7 min, 65%→90% methanol; 7 to 13 min, 90% methanol; 13 to 15 min, 90%→65% methanol; 15 to 20 min, 65% methanol. The collection time was 20 min, the balance time was 3 min, the UV detection wavelengths were 205 nm and 253 nm. The flow rate was 1.0 ml/min and the column temperature was 35℃. The amount of inlet was 10 µl. Results The method was highly specific, and both DOX·HCl and LND exhibited good linearity in the concentration range of 1-40 µg/ml and 6-240 µg/ml, respectively. The two compounds’ precision, stability, and recovery satisfied the requirements of the method. Conclusion This study established a HPLC method that was suitable for the simultaneous detection of DOX·HCl and LND. This method’s high level of specificity, accuracy, and reliability . [ABSTRACT FROM AUTHOR]

Abstract Background In the dapagliflozin (DPF) synthesis, 5-Bromo-2-chlorobenzoic acid (5-BC impurity) and 4-Bromo-1-chloro-2-(4-ethoxybenzyl) benzene (4-BC impurity) are used as starting and reagent sources, respectively. The presence of 5-BC and 4-BC impurities in DPF could potentially affect the effectiveness of the final DPF product. The purpose of this investigation was to develop a stability indicating HPLC methodology for the separation of DPF, its process-related impurities and degradants. The method of analysis was developed on Xbridge Phenyl C18 column of dimensions, 250 × 4.6 mm, 5 μm with gradient elution using mobile phase made up of 0.05% aqueous trifluoroacetic acid and acetonitrile (AcN). Results The method proposed indicates a good linearity (R 2 = 0.9996 and 0.9993), good system precision (RSD ≤ 2%), good method precision (RSD ≤ 2%), accuracy (50–150%), LOD (0.000053 ppm and 0.0000165 ppm) and LOQ (0.00016 ppm and 0.00005 ppm) for 4-BC impurity and 5-BC impurity, respectively. LC–MS was used to detect and characterise degradants that were obtained in acid and base condition were identified and characterised. A comparison of the fragmentation pattern of the [M + H] + ions of DPF and its degradation products revealed the most likely processes for the generation of degradation products. Conclusion DPF sample quality can be evaluated using the suggested method for the presence of 4-BC impurity, 5-BC impurity and 2-(3-(4-ethoxy benzyl)-4-chloro phenyl)-tetrahydro-6-(hydroxy methyl)-2H-pyran-3,4,5-triol.

We characterized thermally polymerized organo‐silica hybrid monolithic capillaries to test their applicability in the gradient elution of peptides. We have used a single‐pot approach utilizing 3‐(methacryloyloxy)propyltrimethoxysilane (MPTMS), ethylene dimethacrylate (EDMA), and n‐octadecyl methacrylate (ODM) as functional monomers. The organo‐silica monolith containing MPTMS and EDMA was compared with the stationary phase prepared by adding ODM to the original polymerization mixture. Column prepared using a three‐monomer system provided a lower accessible volume of flow‐through pores, a higher proportion of mesopores, and higher efficiency. We utilized isocratic and gradient elution data to predict peak widths in gradient elution. Both protocols provided comparable results and can be used for peptide peak width prediction. However, applying gradient elution data for peak width prediction seems simpler. Finally, we tested the effect of gradient time on achievable peak capacity in the gradient elution of peptides with a column prepared with a three‐monomer system providing a higher peak capacity. However, the performance of hybrid organo‐silica monolithic stationary phases in gradient elution of peptides must be improved compared to other monolithic stationary phases. The limiting factor is column efficiency in highly aqueous mobile phases, which needs to be focused on. [ABSTRACT FROM AUTHOR]

Background: In the dapagliflozin (DPF) synthesis, 5-Bromo-2-chlorobenzoic acid (5-BC impurity) and 4-Bromo-1-chloro-2-(4-ethoxybenzyl) benzene (4-BC impurity) are used as starting and reagent sources, respectively. The presence of 5-BC and 4-BC impurities in DPF could potentially affect the effectiveness of the final DPF product. The purpose of this investigation was to develop a stability indicating HPLC methodology for the separation of DPF, its process-related impurities and degradants. The method of analysis was developed on Xbridge Phenyl C18 column of dimensions, 250 × 4.6 mm, 5 μm with gradient elution using mobile phase made up of 0.05% aqueous trifluoroacetic acid and acetonitrile (AcN). Results: The method proposed indicates a good linearity (R2 = 0.9996 and 0.9993), good system precision (RSD ≤ 2%), good method precision (RSD ≤ 2%), accuracy (50–150%), LOD (0.000053 ppm and 0.0000165 ppm) and LOQ (0.00016 ppm and 0.00005 ppm) for 4-BC impurity and 5-BC impurity, respectively. LC–MS was used to detect and characterise degradants that were obtained in acid and base condition were identified and characterised. A comparison of the fragmentation pattern of the [M + H] + ions of DPF and its degradation products revealed the most likely processes for the generation of degradation products. Conclusion: DPF sample quality can be evaluated using the suggested method for the presence of 4-BC impurity, 5-BC impurity and 2-(3-(4-ethoxy benzyl)-4-chloro phenyl)-tetrahydro-6-(hydroxy methyl)-2H-pyran-3,4,5-triol. [ABSTRACT FROM AUTHOR]

In this paper, the fingerprints of 10 batches of Angelica sinensis herbs and 5 batches of commercially available Angelica sinensis preparations originating from different parts of China were determined by high-performance liquid chromatography (HPLC) fingerprinting using a methanol-acetonitrile solution system with linear gradient elution, and the similarity analyses were applied for the classification. Derringer’s satisfaction function evaluated the acceptable limit values for processing multiple characteristic peaks of Angelica sinensis herbs. The results showed that under selected chromatographic conditions, HPLC fingerprints of Angelica sinensis were obtained, and four characteristic peaks were calibrated. The similarities of 10 batches of Angelica sinensis herbs ranged from 0.953 to 0.998, and those of 5 batches of Angelica sinensis preparations ranged from 0.969 to 0.999. The method established in this paper is stable, reliable and reproducible, and it can be used to provide a reference for quality control of the herbs of Angelica sinensis and the drinkable tablets of Angelica sinensis body and to provide a reference for quality control of the classic prescriptions containing Angelica sinensis or the It can provide a reference for the quality control of Angelica sinensis herb and Angelica sinensis body tablets, and provide a basis for the development and research of classical prescriptions containing Angelica sinensis or Angelica sinensis.

Vilanterol (VT) and fluticasone furoate (FF) are components recently used in dry powder inhaler (DPI) to be administered to patients with respiratory diseases, such as asthma or chronic obstructive pulmonary disease (COPD). In the present study, an approach to the analytical procedure development and validation is presented. Next generation impactor (NGI) and high performance liquid chromatography (HPLC) with UV detector were applied to determine the two compounds and the fine particle dose (FPD) of each active ingredient in DPI. The most satisfying chromatographic separation was obtained on Poroshell SB C8 (100 mm × 4.6 mm, 2.7 µm) column applying gradient elution by phosphonate buffer and acetonitrile. VT and FF were detected on a UV detector at wavelengths of 210 nm and 245 nm, respectively. Among the various coating agents, 4% polyethylene glycol PEG 200 in acetone (w/v) was selected as the most effective. Despite the various physicochemical properties of VT and FF, the analytical procedure allows to simultaneously determine two compounds at different wavelengths. The limit of quantitative (LOQ) of vilanterol and fluticasone furoate were determined as 0.049 µg/mL and 0.032 µg/mL, respectively, which is desirable to determine the FPD of active ingredients in microdoses in DPI. The analytical procedure was determined as linear and accurate in the range of LOQ - 2.5 µg/mL and LOQ - 10.0 µg/mL of VT and FF, respectively. The coefficient of determination (R2) was found to be 0.9999 and 1.000 for VT and FF, respectively. [ABSTRACT FROM AUTHOR]

Superficially porous particle (SPP) columns have gained considerable momentum over fully porous particle (FPP) columns among many chromatographers. However, despite several advantages, the SPP columns are not always been used effectively with traditional HPLC. The present study explores the possibility of reducing the runtime of HPLC methods using SPP column technology without compromising the efficiency of high-throughput analysis using conventional HPLC systems. An optimized method was developed by exploiting the advantages of SPP column technology and its effectiveness demonstrated in two separate SPP columns, Kinetex EVO C18 and Accucore C18. By altering method parameters such as flow rate, gradient time, and photodiode array (PDA) detector acquisition rate, we showed that an optimized method is more efficient than the regular method. The experimental results showed significant improvement in peak capacity, peak symmetry, theoretical plate numbers, and peak resolution for the SPP column within a short runtime of 7 min. We demonstrated that the present optimized method helped to reduce runtime by 50% and provide ~ 31% net organic solvent savings, exhibiting a greener approach to methods and method development. [ABSTRACT FROM AUTHOR]

The goal of this study was to provide a new, easy, accurate, cost-effective, exact, sensitive, specific, robust, and rugged method for quantifying Epigallocatechin 3 gallate in wistar rat plasma using reverse phase high-performance chromatography (RP-HPLC). The stationary phase was a Zorbax SB C18 5µ (4.6*150) mm column, while the mobile phase was water with 0.1 percent formic acid (A) and acetonitrile (ACN) with 0.08 percent formic acid (B). The experiment was conducted at 30°C with a flow rate of 1.0 ml/min with PDA detectors at 274 nm. With an r2 of 0.9999, the method was shown to be linear in the concentration range of 0.2-25 µg/ml. At the same retention time (Rt) of epigallocatechin 3 gallate, no interference of co-eluting peaks of endogenous chemicals from the biological matrix was found. The intraday and interday precision RSD (%) was found to be within acceptable limits (less than 2%). The overall mean recovery percentage was determined to be 96.92 %. The LOD and LOQ were determined to be 0.0682 ± 0.0011 µg/ml and 0.205 ± 0.004 µg/ml, respectively. In short-term and long-term stability tests, auto sampler, bench-top, and freeze-thaw stability tests were found to be stable. The developed approach reported was determined to be well within acceptable limits. As a result, in the future, this method can be successfully employed in clinical laboratories to estimate epigallocatechin 3 gallate alone or in conjunction with other analytes or markers in pharmacokinetic, bioequivalence, and therapeutic drug monitoring. [ABSTRACT FROM AUTHOR]

Copyright of Precious Metals / Guijinshu is the property of Precious Metals Editorial Office and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

A method is proposed for the HPLC separation of a mixture of carboxylic acids on a porous graphitized Hypercarb adsorbent under the conditions of gradient elution with formic acid solutions. The analytes were detected using a single quadrupole mass spectrometer. The stepwise gradient of formic acid without an addition of an organic solvent made it possible to achieve good resolution of the analyte peaks and decrease the limits of detection by a factor of 4.4–17.8 compared to their separation with 0.1% formic acid under isocratic conditions. The effect of methanol on the separation of analytes is less pronounced. [ABSTRACT FROM AUTHOR]

A new optimization strategy based on the mixed quantitative structure– retention relationship (QSRR) model is proposed for improving the RPHPLC separation of aripiprazole and its impurities (IMP A-E). Firstly, experimental parameters (EPs), namely mobile phase composition and flow rate, were varied according to Box–Behnken design and thereafter, an artificial neural network (ANN) as a QSRR model was built correlating EPs and selected molecular descriptors (ovality, torsion energy and non-1,4-van der Waals energy) with the log-transformed retention times of the analytes. Values of the root mean square error (RMSE) were used for an estimation of the quality of the ANNs (0.0227, 0.0191 and 0.0230 for the training, verification and test set, respectively). The separations of critical peak pairs on chromatogram (IMP AB and IMP D-C) were optimized using ANNs for which the EPs served as inputs and the log-transformed separation criteria s as the outputs. They were validated by application of leave-one-out cross-validation (RMSE values 0.065 and 0.056, respectively). The obtained ANNs were used for plotting response surfaces upon which the analyses chromatographic conditions resulting in optimal analytes retention behaviour and the optimal values of the separation criteria s were defined. The optimal conditions were 54 % of methanol at the beginning and 79 % of methanol at the end of gradient elution programme with a mobile phase flow rate of 460 μL min-1.

Pavel Jandera was a world‐leading analytical chemist who devoted his entire professional life to research in the field of high‐performance liquid chromatography. During his scientific career, he worked at the Department of Analytical Chemistry at the University of Pardubice, Czech Republic. His greatest contribution to the field of liquid chromatography was the introduction of a comprehensive theory of liquid chromatography with programmed elution conditions. He was also involved in the research of gradient elution techniques in preparative chromatography, modeling of retention and selectivity in various phase systems, preparation of organic monolithic microcolumns, and, last but not least, in the development of theory and practical applications of two‐dimensional liquid chromatography, mainly in the comprehensive form. In this review article, we have tried to capture the highlights of his scientific career and provide the readers with a detailed overview of Pavel Jandera's contribution to the evolution of separation sciences. [ABSTRACT FROM AUTHOR]

Retention prediction of monoamine neurotransmitters has been compared for the generally applied linear solvent‐strength model and quadratic polynomial three‐parameter model. The design of experiments protocol has been applied to plan linear gradients within the experimental space with altered gradient time, mobile phase flow rate, and column temperature. Relative prediction errors increased at elevated temperature, which is more significant for the linear solvent‐strength model when compared to the polynomial model. On the other hand, the predefined design of experiments space controls the retention time errors, as predictions for LC conditions that are outside of the plan are much less accurate and should be avoided. The final part of the work deals with the effect of extracolumn band dispersion on the peak capacity of linear gradients at various gradient times, mobile phase flow rates, and column temperature. The peak capacity determined for corrected experimental data were consistent with the published results dealing with the optimization of peak capacity in gradient elution. [ABSTRACT FROM AUTHOR]

This paper describes an approach to rapidly and easily calculate the linear solvent strength parameters, namely log k0 and S, under reversed‐phase liquid chromatography conditions. This approach, which requires two preliminary gradient experiments to determine the retention parameters, was applied to various representative compounds including small molecules, peptides, and proteins. The retention time prediction errors were compared to the ones obtained with a commercial HPLC modeling software, and a good correlation was found between the values. However, two important constraints have to be accounted for to maintain good predictions with this new approach: i) the retention factor at the initial composition of the preliminary gradient series have to be large enough (i.e., log ki above 2.1) and ii) the retention models have to be sufficiently linear. While these two conditions are not always met with small molecules or even peptides, the situation is different with large biomolecules. This is why our simple calculation method should be preferentially applied to calculate the linear solvent strength parameters of protein samples. [ABSTRACT FROM AUTHOR]

Chromatographic considerations and requirements in developing general RPLC profiling analytical methods for eluting complex medical device extracts are investigated using linear gradient conditions, based on Abraham general solvation model. The focus of the study is not on the development of a specific RPLC method for a particular extract, but on the general considerations and requirements in retention and peak capacity optimization in the separation of complex unknown extracts, possibly with a high number of components and a wide-ranging diversity in hydrophobicity, volatility, and molecular weight (MW). The published representative RPLC gradient conditions, together with nearly 2000 selected compounds as a representation of potential extractables, are used to correlate the gradient retention time and hydrophobicity ( Log P o / w ) of extractables, both calculated by Abraham solvation model. The hydrophobicity range that each gradient separation condition of defined run time can cover is determined, and the Log P o / w values, at which late-eluting and early-eluting issues occur, are computed as well. It is concluded that the complex medical device extraction samples should be separated by RPLC linear gradient elution, and retention time and peak capacity should be optimized to retain and resolve all extractables components for the discovery of extractables components in the sample. [ABSTRACT FROM AUTHOR]

Copyright of Chemistry & Industry of Forest Products is the property of Chemistry & Industry of Forest Products Editorial Department and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Chinese Journal of Inorganic Analytical Chemistry / Zhongguo Wuji Fenxi Huaxue is the property of Beijing Research Institute of Mining & Metallurgy Technology Group and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Gradient and isocratic liquid chromatography were applied for the simultaneous determination of three preservatives, namely; benzyl alcohol (BA), methyl paraben (MP) and propyl paraben (PP). Separation for both elution modes was carried out using a C18 column kept at 60°C throughout the analysis, accompanied with a flow rate of 2 mL/min and UV detection at 254 nm. Gradient liquid chromatography used a time programme with two solvents (0.1% formic acid and acetonitril), while isocratic elution was performed with 0.1% formic acid: 2-propanol in a ratio of 70:30, v/v. Full validation study was conducted for both separation modes, where both of them were linear over the concentration ranges of 100.0–2000.0, 2.5–100.0, and 2.0–200.0 µg/mL for BA, MP and PP respectively. Using gradient elution, the detection limits for BA, MP, and PP were found to be 50.0, 1.8, and 1.5 µg/mL respectively. The corresponding values in isocratic elution were 60.0, 1.5, and 1.3 µg/mL. On the other hand, the limit of quantification for BA, MP, and PP using gradient mode are 70.0, 2.0, and 1.8 µg/mL respectively. While isocratic elution resulted in corresponding values of: 80.0, 2.3, and 1.7 µg/mL. The accuracy of the proposed method was illustrated from the high percentage recoveries values which were 99.67%, 100.42%, and 99.85% for BA, MP, and PP respectively using gradient mode, with corresponding values of 99.79%, 100.39%, and 99.87% for the isocratic elution mode. In addition, gradient elution was further applied to detect and assay the selected preservatives in different pharmaceutical formulations demonstrating that their quantities are within the stated ranges, and eventually, a comparative overview was introduced.

There are several different approaches for LC method development; beside traditional, different software programs for method development and optimization are available. The solvatic retention model of reversed-phase LC was applied for prediction of retention in the gradient elution mode for aripiprazole and its related substances described in European Pharmacopoeia. As some of these compounds have very similar and others quite different chemical structure, their separation is challenge. Prediction was suitable on examined stationary phases (C18, C8 and phenyl-hexyl) with 0.1% phosphoric acid as aqueous mobile phase and acetonitrile or methanol as organic modifier. Predicted retention times take into account structural formulae of compounds and properties of stationary and mobile phases result in average difference of 14-17% compared to experimental ones on phenyl-hexyl stationary phase, where the highest matching was obtained. After utilisation of the retention models with data from one experimental run, the average difference decrease to maximal 7% and after contribution of data from two experimental runs, to maximal 2%. For majority of studied compounds difference between predicted and experimental values on all examined stationary phases is lower than 3%.

Abstract Background A novel phosphatidyl nanoprodrug system can be selectively released parent drugs in cancer cells, triggered by the local overexpression of phospholipase D (PLD). This system significantly reduces the intrinsic disadvantages of conventional chemotherapeutic drugs. However, the separation and purification processes of phosphatidyl prodrug, the precursor of phosphatidyl nanoprodrug, have not been established, and the preparation of nanocrystals with good stability and tumor-targeting capability is still challenging. Results In this study, we established a successive elution procedure for the phosphatidyl prodrug—phosphatidyl mitoxantrone (PMA), using an initial ten-bed volume of chloroform/methanol/glacial acetic acid/water (26/10/0.8/0.7) (v/v/v/v) followed by a five-bed volume (26/10/0.8/3), with which purity rates of 96.93% and overall yields of 50.35% of PMA were obtained. Moreover, to reduce the intrinsic disadvantages of conventional chemotherapeutic drugs, phosphatidyl nanoprodrug—PMA nanoprodrug (NP@PMA)—was prepared. To enhance their stability, nanoparticles were modified with polyethylene glycol (PEG). We found that nanoprodrugs modified by PEG (NP@PEG–PMA) were stably present in RPMI-1640 medium containing 10% FBS, compared with unmodified nanoprodrug (NP@PMA). To enhance active tumor-targeting efficiency, we modified nanoparticles with an arginine-glycine-aspartic acid (RGD) peptide (NP@RGD–PEG–PMA). In vitro cytotoxicity assays showed that, compared with the cytotoxicity of NP@PEG–PMA against tumor cells, that of NP@RGD–PEG–PMA was enhanced. Thus, RGD modification may serve to enhance the active tumor-targeting efficiency of a nanoprodrug, thereby increasing its cytotoxicity. Conclusions A process for the preparation and purification of novel phosphatidyl prodrugs was successfully established, and the nanoprodrug was modified using PEG for enhanced nanoparticle stability, and using RGD peptide for enhanced active tumor-targeting efficiency. These procedures offer considerable potential in the development of functional antitumor prodrugs.

A nonlinear lumped kinetic model of liquid chromatography is formulated and solved numerically to theoretically investigate the effect of column overloading on gradient elution. Linear solvent strength (LSS) model is utilized for Henry's constant, non linearity coefficient and axial dispersion coefficient. A semi-discrete high-resolution finite volume scheme is extended and applied to obtain the approximate solutions of the governing model equations. The effects of changing modulator concentration are examined on the single and two-component elution. The benefits of gradient elution over isocratic elution are thoroughly discussed. The influences of optimizing free-parameters available in gradient chromatography are analyzed on the efficiency of the column and on the production of targeted components. For instance, the results obtained are used to study the effects of gradient slope, modulator concentration, solvent strength, nonlinearity coefficient, mass transfer coefficient, and axial dispersion coefficient on the concentration profiles. [ABSTRACT FROM AUTHOR]

The determination of glycosylated hemoglobin (HbA 1c) is crucial for diabetes diagnosis and can provide more substantial results than the simple measurement of glycemia. While there is a lack of simple methods for the determination of HbA 1c using a point-of-care test (POCT) compared to glycemia measurement. In particular, high-performance liquid chromatography (HPLC) is considered the current gold standard for determining HbA 1c levels. However, commercial HPLC systems usually have some sort of disadvantages such as bulky size, high-cost and need for qualified operators. Therefore, there is an urgent demand to develop a portable, and fast HbA1c detection system consuming fewer reagents. We present a novel microchip that integrates a micromixer, passive injector, packed column and detection cell. The integrated microchip, in which all the microstructures were formed in the CNC machining center through micro-milling, is small in size (30 mm × 70 mm × 10 mm), and can withstand 1600 psi of liquid pressure. The integrated design is beneficial to reduce the band broadening caused by dead volume. Based on the microchip, a microchip liquid chromatography (LC) system was built and applied to the analysis of HbA 1c. The separation conditions of HbA 1c in blood calibrator samples were optimized using the microchip LC system. Samples containing four levels of HbA 1c were completely separated within 2 min in optimal gradient conditions, with an inaccuracy (<3.2 %), a coefficient of variation (c.v. < 2.1 %) and a correlation coefficient (R2 = 0.993), indicating excellent separation efficiency and reproducibility. The POCT of HbA 1c is critical for diabetes diagnosis. The microchip chromatography system was developed for HbA 1c determination, which contains an integrated microchip and works under a gradient elution. It surpasses existing chip technology in terms of separation performance and detection speed, providing a competitive advantage for POCT of HbA 1c. It is considered one important step for realizing efficient portable systems for timely and accurate diabetes diagnosis. [Display omitted] • A novel microchip integrated multiple chromatographic functional devices. • The three-layer bonded microchip can withstand 1600 psi pressure. • Gradient elution mode can be implemented on the microchip. • Samples containing four percentages of HbA 1c were accurately detected in 2 min. [ABSTRACT FROM AUTHOR]

• Self-disproportionation of enantiomers (SDE) on a silica column was examined. • Isotherm coefficients were correlated with the modifier concentration. • Gradient elution allowed enhancement of SDE and separation selectivity. • Dynamic model was formulated and used to predict the process. The influence of mobile phase composition on the efficiency of enantiomer separation by achiral chromatography (ACh) was investigated. The separation was induced by the phenomenon of self-disproportionation of enantiomers (SDE) triggered by their homo and hetero-chiral interactions in an achiral environment. Typically, SDE occurs in apolar mobile phases of weak elution strength, which causes the separation time to extend and the process productivity to deteriorate. To mitigate that effect, we altered the content of a strong solvent (modifier) in the mobile phase by use of a solvent gradient in which the target enantiomer was separated in the presence of the weak solvent, whereas the unresolved mixture of enantiomers was eluted by increasing the modifier content in the mobile phase. This enabled accelerating the solute elution while preserving the separation selectivity. The approach was examined for the separation of nonracemic mixtures of two structurally different compounds that exhibited the SDE effect in ACh, i.e., metalaxyl (MX) and methyl p -tolyl sulfoxide (MTSO). The target compound of the separation was the more abundant enantiomer in the enantiomeric mixture. The process realization was preceded by the determination of the effect of the modifier content on the separation yield for enantiomeric mixtures of MX and MTSO of different enantiomeric excess (ee). In the case of MX, yield of the pure target enantiomer varied from 2 %, for the maximum concentration of the modifier, to 45 % for the minimum modifier concentration and the largest ee used in the experiments. In the case of MTSO, the yield varied from minimum 40 % to maximum 66 %. To predict the process, we employed a dynamic model, in which underlying thermodynamic dependencies were implemented. [ABSTRACT FROM AUTHOR]

• Theoretical study of possibilities reinforcement learning (RL) for method development. • RL algorithm trained to select optimal scouting runs for retention time modeling. • Three-parameter Neue-kuss retention model considered for simulated data. • Three scouting runs sufficient to retrieve retention parameters adequately. • Preference given to isocratic scouting runs when not penalized for analysis time. Artificial intelligence and machine learning techniques are increasingly used for different tasks related to method development in liquid chromatography. In this study, the possibilities of a reinforcement learning algorithm, more specifically a deep deterministic policy gradient algorithm, are evaluated for the selection of scouting runs for retention time modeling. As a theoretical exercise, it is investigated whether such an algorithm can be trained to select scouting runs for any compound of interest allowing to retrieve its correct retention parameters for the three-parameter Neue-Kuss retention model. It is observed that three scouting runs are generally sufficient to retrieve the retention parameters with an accuracy (mean relative percentage error MRPE) of 1 % or less. When given the opportunity to select additional scouting runs, this does not lead to a significantly improved accuracy. It is also observed that the agent tends to give preference to isocratic scouting runs for retention time modeling, and is only motivated towards selecting gradient scouting runs when penalized (strongly) for large analysis/gradient times. This seems to reinforce the general power and usefulness of isocratic scouting runs for retention time modeling. Finally, the best results (lowest MRPE) are obtained when the agent manages to retrieve retention time data for % ACN at elution of the compound under consideration that spread the entire relevant range of ACN (5 % ACN to 95 % ACN) as well as possible, i.e., resulting in retention data at a low, intermediate and high % ACN. Based on the obtained results, we believe reinforcement learning holds great potential to automate and rationalize method development in liquid chromatography in the future. [ABSTRACT FROM AUTHOR]

A new dimeric aporphine alkaloid, biscocsarmine, 2, together with lirioferine, 1, and cocsarmine, 3, were isolated from the ethanol extract of the stems of Triclisia dictyophylla Diels (Menispermaceae) using a preparative pH-zone refining CCC in a single step. The first solvent system family tested for this fractionation was hexane–ethyl acetate–methanol–water (HEMWat) at a series of solvent ratios, and hydrochloric acid and triethylamine at 5 mM as eluter/retainer. None of these HEMWat ratios, however, gave suitable K for the target alkaloids. Ethyl acetate–n-butanol–water (EBuWat) was tested instead and the selected solvent system was composed of ethyl acetate–n-butanol–water 5:5:10 (v/v), where triethylamine (60 mM) was added to the upper organic stationary phase as a retainer and hydrochloric acid (5 mM) to the aqueous mobile phase as an eluter. The chemical structures of the isolated compounds were elucidated based on comprehensive spectroscopic and spectrometric techniques. This is the first report of aporphine alkaloids in this plant species. [ABSTRACT FROM AUTHOR]

Biological samples in lipidomic studies can consist of extremely complex mixtures due to the diverse range of species and isomerism. Herein, highly efficient, in‐house packed microcapillary columns introduce the potential to better separate these complex mixtures. We compared the effects of changing column length (15, 30, and 60 cm) and inner diameter (75 and 100 μm) on lipid separation efficiency by reversed‐phase gradient analysis using ultrahigh‐pressure liquid chromatography coupled to mass spectrometry with operating pressures ranging from 450 to 2200 bar. Seven lipid standards composed of phosphatidylcholine and triacylglycerol species were analyzed at four different gradient rates to calculate conditional peak capacity. The longest column, 60 cm, at the shallowest gradient of 2% gave the highest peak capacity of 359 with a separation window of 2 h. The intermediate column length of 30 cm with 75 μm inner diameter provided a peak capacity of 287 with a separation window of 1 h. There was no significant difference in peak capacity between 75 and 100 μm inner diameter columns. This study showed that using highly efficient microcapillary columns increased peak capacity and resolution of lipids, and thus, this technique seems promising for enhancing lipid coverage and enabling better discovery of lipid biomarkers. [ABSTRACT FROM AUTHOR]

The structure and composition of polycarbonate polydimethylsiloxane copolymer (PC-co-PDMS) was investigated by applying various analytical approaches including chromatographic separation methods, spectrometric, and spectroscopic detection techniques. In particular, size exclusion chromatography (SEC) and liquid adsorption chromatography operating at different conditions (e.g. using gradient solvent systems) were used to achieve separations according to molar mass and functionality distribution. The coupling of both techniques resulted in fingerprint two-dimensional plots, which could be used to easily compare different copolymer batches. Matrix-assisted laser desorption/ionization-time-of-flight (MALDI-TOF) mass spectrometry was applied for structural investigations. The different ionization behavior of both comonomers, however, strongly limited the applicability of this technique. In contrast to that, Fourier-transform Infrared (FTIR) spectroscopy could be used to quantify the amount of PDMS in the copolymer at different points in the chromatogram. The resulting methodology was capable of distinguishing PC-co-PDMS copolymer from PC homopolymer chains present in the material. [ABSTRACT FROM AUTHOR]

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Gradient and isocratic liquid chromatography were applied for the simultaneous determination of three preservatives, namely; benzyl alcohol (BA), methyl paraben (MP) and propyl paraben (PP). Separation for both elution modes was carried out using a C18 column kept at 60°C throughout the analysis, accompanied with a flow rate of 2 mL/min and UV detection at 254 nm. Gradient liquid chromatography used a time programme with two solvents (0.1% formic acid and acetonitril), while isocratic elution was performed with 0.1% formic acid: 2-propanol in a ratio of 70:30, v/v. Full validation study was conducted for both separation modes, where both of them were linear over the concentration ranges of 100.0–2000.0, 2.5–100.0, and 2.0–200.0 µg/mL for BA, MP and PP respectively. Using gradient elution, the detection limits for BA, MP, and PP were found to be 50.0, 1.8, and 1.5 µg/mL respectively. The corresponding values in isocratic elution were 60.0, 1.5, and 1.3 µg/mL. On the other hand, the limit of quantification for BA, MP, and PP using gradient mode are 70.0, 2.0, and 1.8 µg/mL respectively. While isocratic elution resulted in corresponding values of: 80.0, 2.3, and 1.7 µg/mL. The accuracy of the proposed method was illustrated from the high percentage recoveries values which were 99.67%, 100.42%, and 99.85% for BA, MP, and PP respectively using gradient mode, with corresponding values of 99.79%, 100.39%, and 99.87% for the isocratic elution mode. In addition, gradient elution was further applied to detect and assay the selected preservatives in different pharmaceutical formulations demonstrating that their quantities are within the stated ranges, and eventually, a comparative overview was introduced. [ABSTRACT FROM AUTHOR]

• A new methanol linear gradient CCC was introduced based on HepEMWat solvent systems. • Tedious preparations of solvent systems and waste of solvent was avoided. • This method can increase the range of K values separated in a single separation. • 12 compounds were highly enriched from Sinopodophyllum hexandrum in one-step separation. Counter-current chromatography (CCC) is a unique, liquid-liquid partition chromatography process. Both the mobile and stationary phases are liquids, so no solid support matrix is used. CCC has gained wide acceptance as a preparative technique in a variety of fields. Because the mobile and stationary phases are both liquids, gradient elution is difficult to perform with CCC. Phase equilibrium must be maintained, so any change in the composition of one phase may induce a compositional change in the other. In this work, a new linear gradient elution method was developed for CCC. Biphasic solvent systems containing heptane, ethyl acetate, methanol, and water (HepEMWat) in various ratios were prepared and used to optimize both isocratic and linear gradient CCC separation with methanol. We first separated a test mixture of four standard compounds with partition coefficients ranging from 0.8 to 7.8. The separation resembled a reversed-phase process, and elution was performed while progressively decreasing the polarity of the mobile phase. Target molecules with small partition coefficients eluted first in the lower phase of the optimized HepEMWat solvent system. Elution of constituents with large partition coefficients was quite slow under isocratic conditions. Separation time was significantly reduced when elution was performed with a linear gradient using methanol and the optimal HepEMWat system. Elution with a 3:7:4:6 (v/v/v/v) HepEMWat system took approximately 200 min. This included an 80-min isocratic step, followed by gradient elution with methanol from 0% to 30%. The optimized methanol linear gradient CCC method was then used to separate a complex mixture of natural products isolated from Sinopodophyllum hexandrum (Royle) Ying roots. Twelve compounds with a wide range of polarities were well-resolved in a single separation. We have developed a convenient and cost-effective strategy for the separation of complex mixtures. No tedious mobile phase preparation step is required. The volume of unused mobile phase is minimal, so little solvent is wasted. The method is an important advance for the separation of mixtures that contain many compounds with a large range of polarities and partition coefficients, which are common features of natural products. [ABSTRACT FROM AUTHOR]

There are several different approaches for LC method development; beside traditional, different software programs for method development and optimization are available. The solvatic retention model of reversed-phase LC was applied for prediction of retention in the gradient elution mode for aripiprazole and its related substances described in European Pharmacopoeia. As some of these compounds have very similar and others quite different chemical structure, their separation is challenge. Prediction was suitable on examined stationary phases (C18, C8 and phenyl-hexyl) with 0.1% phosphoric acid as aqueous mobile phase and acetonitrile or methanol as organic modifier. Predicted retention times take into account structural formulae of compounds and properties of stationary and mobile phases result in average difference of 14-17% compared to experimental ones on phenyl-hexyl stationary phase, where the highest matching was obtained. After utilisation of the retention models with data from one experimental run, the average difference decrease to maximal 7% and after contribution of data from two experimental runs, to maximal 2%. For majority of studied compounds difference between predicted and experimental values on all examined stationary phases is lower than 3%. [ABSTRACT FROM AUTHOR]

• Re-parameterized Neue-Kuss model is reported. • Re-parameterization improves accuracy and precision of results. • Experimental design for gradient elution is reported. • Reported design allows for accurate prediction of isocratic retention factors. The present work describes a re-parameterization of the Neue Kuss (NK) model for describing retention in liquid chromatography, and this re-parameterized model is used to fit a large set of isocratic retention measurements with improved convergence properties relative to the original parameterization of the model. Next, an experimental design for retention measurements using mobile phase gradient elution conditions is proposed for the purpose of obtaining accurate and precise NK parameters. Simulated retention data for mobile phase gradient elution conditions with two different levels of noise, as well as an essentially zero noise level were fit with the re-parameterized model. The results showed that the re-parameterized fits yielded average (absolute value) prediction errors for the parameters at the highest noise level of 7.2 % for S 1,ref , 18 % for S 2,ref and 6.2 % for k ref (the re-parameterized NK model parameters). These errors were significantly smaller than those for the original parameterization of the NK model, where the errors were 23 % for S 1 , 25 % for S 2 and 160 % for k w (the original NK model parameters). Furthermore, isocratic retention factors predicted using these model parameters were found to have an average magnitude of error of 0.51 % for the re-parameterized model, as opposed to 6800 % for the model with the original parameterization. A further test of this approach was carried out for independent experimental measurements for five solutes on a C18 column. The average magnitude of error of the isocratic retention factors predicted from parameters obtained from fits of gradient data was 1.6 %, provided that the range of organic solvent compositions that the solute sampled in the mobile phase gradient experiments was consistent with the isocratic experiments. These results indicate that the re-parameterization of the NK model allows for significant improvements in the fitting process, and that the proposed experimental design allows for NK parameters to be extracted from mobile phase gradient experiments, with prediction accuracies of isocratic retention factors on the order of 1-2 %. [ABSTRACT FROM AUTHOR]

This paper aims to establish a detection method for simultaneous determining four additives in flour products: one simultaneously determines the acesulfame, sodium cyclamate, bromate, and calcium propionate through the selection of ion chromatography pump flow rate, injection volume, eluent concentration, optimization of sample pretreatment and the influence of interfering ions. When using the pump flow rate of 0.8 ml/min, 200 µL large volume injection, 0-14 min, 14-25 min eluent concentration 30 mmol/L gradient elution, 25-26 min eluent concentration 6 mmol/L, flour product is pulverized after addition of water vortex ultrasonic extraction, the supernatant by C18 solid phase extraction (SPE) columns and silver filter, 0.22μm water phase porous membrane testing on the machine, the detection limits of the four kinds of targets are 0.16 μg/ml, 0.19 μg/ml, 0.24 μg/ml, and 0.38 μg/ml, respectively; The standard deviations of retention time and peak area are calcium propionate, respectively 0.13~0.42%, 2.14~4.25% ; bromate 0.20~0.67%, 1.33~4.52% ; sodium cyclamate 0.14~0.53%, 3.57~5.62% ; acesulfame potassium 0.64~0.93%, 0.42~5.81%. This method uses water as the sole extraction solvent and can detect four additives in flour products in a single test. And the pretreatment process is also very simple. When it is applied to other food tests, some compounds may cause interference, which can be assisted by other testing methods.

• Simulations of both gradient and uniform mixed-mode LC columns are described. • Peak focusing is noted on stationary phase gradients under mobile phase gradients. • Orientation of stationary phase gradients effects peak width and retention time. • Experimental and simulation differences may suggest neighboring ligand effects. This work seeks to explore and understand the effects of column orientation and degree of modification of continuous stationary phase gradient columns under a mobile phase gradient using both simulations and experiments. Peak parameters such as retention times, peak widths and resolution are obtained for five phenolic compounds on a C 18 -silica gradient stationary phase. Simulations show that peak widths for the solutes are dependent upon the fractional composition of C 18 and orientation of the stationary phase gradient when coupled to a mobile phase gradient. Also, when compared to a simulated uniform mixed-mode column, peak widths reach a minimum on the gradient column with a coverage higher than 50% C 18 where the column is oriented to have the C 18 dense region at the end. Experimentally, continuous stationary phase gradients were fabricated to have a total C 18 composition of 78% of the original uniform column with an exponential profile using a previously described destructive controlled rate infusion method. Under gradient mobile phase conditions, experimental retention times for the gradient column showed a significant increase compared to the original 100% C 18 column. Simulations with a similar C 18 composition, however, predicted decreased retention times from the original C 18 column. A statistical increase in the retention time of protocatechuic acid and decrease in the peak width of tyrosol, caffeic acid, and coumaric acid were noted when the gradient column was oriented to have the C 18 dense region located near the detector. Collectively, combining gradients in both the mobile and stationary phases can yield interesting neighboring ligand effects and peak broadening/focusing effects. [ABSTRACT FROM AUTHOR]

This work describes a novel sequential injection chromatography (SIC) method combined with linear gradient elution for the separation and determination of three main methylxanthines (theobromine, theophylline and caffeine) using a short C18 monolithic column. The method utilizes a hybrid manifold which exploits zone fluidics for solution manipulation and programmable fluidics for the implementation of a two-solvent linear gradient elution protocol. This approach offers a high degree of automation and enables faster separation of the three target methylxanthines with respect to isocratic elution as well as better chromatographic efficiency. The limits of detection of the three methylxanthines ranged from 0.18 to 0.45 μmol L−1, the instrumental repeatability (at the 10 μmol L−1 level of the target compounds, n = 6) was ≤2% and the separation time was 3.3 min. The SIC method was validated and applied to the analysis of coffee, chocolate and tea samples. Image 1 • A linear gradient sequential injection chromatography approach was developed. • Linear gradient elution was implemented using programmable fluidics. • The method was applied to the determination of three methylxanthines. • The methodology presents distinct advantages over the isocratic elution mode. • The method proved accurate, precise, robust and fit-for-purpose. [ABSTRACT FROM AUTHOR]

• Pulses largely reduce retention of hydrophobic solutes at low modifier contents. • Intra-column delays should be considered to get good predictions close to the pulses. • Designs with pulses provide model parameters that agree with isocratic experiments. • Out-of-domain predictive capability of pulse designs is excellent. • Analysis times and solvent consumption are also competitive. The advantages and disadvantages of the use of isocratic experimental designs including transient increments of organic solvent (i.e., pulses) in the mobile phase(s) of lowest elution strength are explored with modelling purposes. For retained solutes, this type of mixed design offers similar or better predictive capability than gradient designs, shorter measurement time than pure isocratic designs, and retention model parameters that agree with those derived from pure isocratic experiments, with similar uncertainties. The predicted retention times are comparable to those offered by models adjusted from pure isocratic designs, and the solvent waste is appreciably lower. Under a practical standpoint, mixed designs including pulse(s) can be easily constructed by replacing the slowest isocratic runs with runs containing a pulse of short duration at an intermediate time. This allows the elution of the fastest solutes with appreciable retention in the initial sector of the elution program, previous to the pulse, and the elution of the slow solutes after the pulse, also in acceptable times. The fitting of the retention data obtained with pulses is simpler compared to gradient elution, and involves solving the integral equation of gradient elution, simplified by the presence of isocratic sectors. Experiments involving pulses reveal the existence of discrepancies in the predictions for solutes eluting in the nearby of the pulse, offered by the fundamental equation of gradient elution when this is solved using numerical integration. The correction of such discrepancies implies the inclusion of intra-column delays, in the arrival of changes in the concentration of organic modifier in the gradient to the instantaneous position of the solute, along the whole migration. [ABSTRACT FROM AUTHOR]