Intelligent Recommendation Systems Powered by Consensus Neural Networks: The Ultimate Solution for Finding Suitable Chiral Chromatographic Systems?

The selection of suitable combinations of chiral stationary phases (CSPs) and mobile phases (MPs) for the enantioresolution of chiral compounds is a complex issue that often requires considerable experimental effort and can lead to significant waste. Linking the structure of a chiral compound to a CSP/MP system suitable for its enantioseparation can be an effective solution to this problem. In this study, we evaluate algorithmic tools for this purpose.

Potential of sodium dodecyl sulfate micellar solutions as eluents in magnetic dispersive micro-solid phase extraction with polydopamine-coated magnetite nanoparticles. Application to antidepressant drugs.

In this paper, the potential of micellar solutions of the anionic surfactant sodium dodecyl sulfate (SDS) as eluents in dispersive micro-solid phase extraction (D-μSPE) using polydopamine-coated magnetite nanoparticles (FeO@PDA NPs) for the extraction and preconcentration of seven basic drugs (bupropion, citalopram, fluoxetine, mianserin, nomifensine, trimipramine, and viloxazine) is explored for the first time (to the best to our knowledge) and compared with conventional hydro-organic eluents. The impact of the sample solution pH, FeO@PDA NPs and PDA coating amounts and extraction time on the extraction efficiency (EE), as well as the composition of the eluent on the overall efficiency (OE) are studied. Under the selected experimental conditions (50 mg of FeO@PDA NPs, 100 μL of 1 M NH, 5 min of extraction time and 0.

Comparative study on retention behaviour and enantioresolution of basic and neutral structurally unrelated compounds with cellulose-based chiral stationary phases in reversed phase liquid chromatography-mass spectrometry conditions.

A comparative study on the retention behaviour and enantioresolution of 54 structurally unrelated neutral and basic compounds using five commercial cellulose-based chiral stationary phases (CSPs) and hydro-organic mobile phases compatible with MS detection is performed. Four phenylcarbamate-type cellulose CSPs (cellulose tris(3,5-dimethylphenylcarbamate), Cell1; cellulose tris(3-chloro-4-methylphenylcarbamate), Cell2; cellulose tris(4-chloro-3-methylphenylcarbamate), Cell4 and cellulose tris(3,5- dichlorophenylcarbamate), Cell5) and one benzoate-type cellulose CSP (cellulose tris(4-methylbenzoate), Cell3) are assayed. Mobile phases consist of binary mixtures of methanol (30-90% MeOH) or acetonitrile (10-98% ACN) with 5 mM ammonium bicarbonate (pH = 8.

Artificial neural networks to model the enantioresolution of structurally unrelated neutral and basic compounds with cellulose tris(3,5-dimethylphenylcarbamate) chiral stationary phase and aqueous-acetonitrile mobile phases.

Artificial neural networks (ANN; feed-forward mode) are used to quantitatively estimate the enantioresolution (Rs) in cellulose tris(3,5-dimethylphenylcarbamate) of chiral molecules from their structural information. To the best of our knowledge, for the first time, a dataset of structurally unrelated compounds is modelled using ANN, attempting to approach a model of general applicability. After setting a strategy compatible with the data complexity and their relatively limited size (56 molecules), by prefixing initial ANN inner weights and the validation and cross-validation subsets, the ANN optimisation based on a novel quality indicator calculated from 9 ANN outputs allows selecting a proper (predictive) ANN architecture (a single hidden layer of 7 neurons) and performing a forward-stepwise feature selection process (8 variables are selected).

Reversed phase liquid chromatography for the enantioseparation of local anaesthetics in polysaccharide-based stationary phases. Application to biodegradability studies.

A comprehensive study on the chiral separation of bupivacaine, mepivacaine, prilocaine and propanocaine with eight commercial polysaccharide-based chiral stationary phases (CSPs) in reversed phase conditions compatible with MS detection is performed. Methanol and acetonitrile are used as organic modifiers. Retention and resolution values obtained for each compound in the different CSPs and mobile phases are compared.

Comparative modelling study on enantioresolution of structurally unrelated compounds with amylose-based chiral stationary phases in reversed phase liquid chromatography-mass spectrometry conditions.

Polysaccharide-based chiral stationary phases (CSPs) are the most used chiral selectors in HPLC. These CSPs can be used in normal, polar organic and aqueous-organic mobile phases. However, normal and polar organic mobile phases are not adequate for chiral separation of polar compounds, for the analysis of aqueous samples and for MS detection.

Improved accuracy of environmentally relevant parameter estimates derived from biodegradation assays.

Biodegradation assays involve both biodegradation and analytical processes which can be affected by systematic errors, among others. These errors can affect all the environmentally relevant parameters related to biodegradability, enantioselectivity (in the case of chiral compounds), kinetic parameters and persistence of chemicals. However, such impacts have never been well-characterized.

Anticipating the impact of pitfalls in kinetic biodegradation parameter estimation from substrate depletion curves of organic pollutants.

Accurate and reliable estimation of kinetic parameters of pollutant biodegradation processes is essential for environmental and health risk assessment. Common biodegradation models proposed in the literature, such as the nonlinear Monod equation and its simplified versions (e.g.

Direct chromatographic study of the enantioselective biodegradation of ibuprofen and ketoprofen by an activated sludge.

The quantification of the enantiomeric fraction (EF) during the biodegradation process is essential for environmental risk assessment. In this paper the enantioselective biodegradation of ibuprofen, IBU, and ketoprofen, KET, two of the drugs most consumed, was evaluated. Biodegradation experiments were performed in batch mode using a minimal salts medium inoculated with an activated sludge (collected from a Valencian Waste Water Treatment Plant) and supplemented with the racemate of each compound.

Modelling the enantioresolution capability of cellulose tris(3,5-dichlorophenylcarbamate) stationary phase in reversed phase conditions for neutral and basic chiral compounds.

To the best of our knowledge, the prediction of the enantioresolution ability of polysaccharides-based stationary phases in liquid chromatography for structurally unrelated compounds has not been previously reported. In this study, structural information of neutral and basic compounds is used to model their enantioresolution levels obtained from an immobilised cellulose tris(3,5-dichlorophenylcarbamate) stationary phase in reversed phase conditions. Thirty-four structurally unrelated chiral drugs and pesticides, from seven families, are studied.

Trimeprazine is enantioselectively degraded by an activated sludge in ready biodegradability test conditions.

A great number of available pharmaceuticals are chiral compounds. Although they are usually manufactured as racemic mixtures, they can be enantioselectively biodegraded as a result of microbial processes. In this paper, a biodegradability assay in similar conditions to those recommended in OECD tests of enantiomers of trimeprazine (a phenothiazine employed as a racemate) is carried out.

Enantioresolution in electrokinetic chromatography-complete filling technique using sulfated gamma-cyclodextrin. Software-free topological anticipation.

Few papers have tried to predict the resolution ability of chiral selectors in capillary electrophoresis for the separation of the enantiomers of chiral compounds. In a previous work, we have used molecular information available on-line to establish enantioresolution levels of basic compounds using highly sulfated β-CD (HS-β-CD) as chiral selector in electrokinetic chromatography-complete filling technique (EKC-CFT). The present study is a continuation of this previous work, introducing some novelties.

Fit-for-purpose chromatographic method for the determination of amikacin in human plasma for the dosage control of patients.

In this paper, a simple, rapid and sensitive method based on liquid chromatography with fluorimetric detection (HPLC-FLD) for the determination of amikacin (AMK) in human plasma is developed. Determination is performed by pre-column derivatization of AMK with ortho-phtalaldehyde (OPA) in presence of N-acetyl-L-cysteine (NAC) at pH 9.5 for 5 min at 80 °C.

Evaluation of the enantioselective binding of imazalil to human serum albumin by capillary electrophoresis.

In this work, a methodology for the evaluation of enantioselective binding of imazalil (IMA) enantiomers to human serum albumin (HSA) that does not require the separation of free and bound to HSA fractions is developed. This methodology comprises the incubation of IMA-HSA designed mixtures for 30 min directly in the capillary electrophoresis system and the subsequent direct injection and chiral separation of IMA employing highly sulfated β-cyclodextrin as chiral selector and the complete filling technique. Two mathematical approaches were used to estimate apparent affinity constants (K1), protein binding and enantioselectivity (ES) for both enantiomers of IMA.

Fast-multivariate optimization of chiral separations in capillary electrophoresis: anticipative strategies.

The design of experiments (DOE) is a good option for rationally limiting the number of experiments required to achieve the enantioresolution (Rs) of a chiral compound in capillary electrophoresis. In some cases, the modeled Rs after DOE analysis can be unsatisfactory, maybe because the range of the explored factors (DOE domain) was not the adequate. In these cases, anticipative strategies can be an alternative to the repetition of the process (e.

Cyclodextrins in capillary electrophoresis: recent developments and new trends.

Despite the fact that extensive research in the field of separations by capillary electrophoresis (CE) has been carried out and many reviews have been published in the last years, a specific review on the use and future potential of cyclodextrins (CDs) in CE is not available. This review focuses the attention in the CD-CE topic over the January 2013-February 2014 period (not covered by previous more general CE-reviews). Recent contributions (reviews and research articles) including practical uses (e.

Fast evaluation of enantioselective drug metabolism by electrophoretically mediated microanalysis: application to fluoxetine metabolism by CYP2D6.

In this work, a capillary electrophoretic methodology for the enantioselective in vitro evaluation of drugs metabolism is applied to the evaluation of fluoxetine (FLX) metabolism by cytochrome 2D6 (CYP2D6). This methodology comprises the in-capillary enzymatic reaction and the chiral separation of FLX and its major metabolite, norfluoxetine enantiomers employing highly sulfated β-CD and the partial filling technique. The methodology employed in this work is a fast way to obtain a first approach of the enantioselective in vitro metabolism of racemic drugs, with the additional advantage of an extremely low consumption of enzymes, CDs and all the reagents involved in the process.

Modeling the chiral resolution ability of highly sulfated β-cyclodextrin for basic compounds in electrokinetic chromatography.

Despite the fact that extensive research in the field of enantioseparations by capillary electrophoresis has been carried out, it is difficult to predict whether a concrete chiral selector would be useful for the separation of a racemic compound. Hence, several experimental effort is necessary to test the abilities of individual chiral selectors, usually by trial and error procedures. Thus, the enantioseparation of a new racemate becomes a time- and money-consuming task.

In-line capillary electrophoretic evaluation of the enantioselective metabolism of verapamil by cytochrome P3A4.

In this paper a methodology for the in-line evaluation of enantioselective metabolism by capillary electrophoresis has been developed and applied to the study of verapamil metabolism by cytochrome P3A4. The developed methodology comprises an in-capillary reaction step carried out by electrophoretically mediated microanalysis and a separation step in which highly sulfated β-cyclodextrin with partial filling technique has been employed as chiral selector for verapamil and norverapamil enantiomers resolution, joining the advantages of both methodologies in a unique assay. Kinetic parameters of the enzymatic reaction (Km and Vmax) have been evaluated for both verapamil enantiomers by non-linear fitting of experimental data obtained under intermediate precision conditions to Michaelis-Menten equation.

Characterizing the interaction between enantiomers of eight psychoactive drugs and highly sulfated-β-cyclodextrin by counter-current capillary electrophoresis.

The estimation of apparent binding constants and limit mobilities of the complexes of the enantiomers that characterize the interaction of enantiomers with chiral selectors, in this case highly sulfated β-cyclodextrin, was approached using a simple and economic electrophoretic modality, the complete filling technique (CFT) in counter-current mode. The enantiomers of eight psychoactive drugs, four antihistamines (dimethindene, promethazine, orphenadrine and terfenadine) and four antidepressants (bupropion, fluoxetine, nomifensine and viloxazine) were separated for the first time for this cyclodextrin (CD). Estimations of thermodynamic and electrophoretic enantioselectivies were also performed.

Determination of fluoxetine enantiomers in pharmaceutical formulations by electrokinetic chromatography-counter current technique.

In this work, an electrokinetic chromatography-counter current procedure for the separation of fluoxetine enantiomers using highly sulfated β-cyclodextrin was optimized and applied to the determination of the enantiomers in three pharmaceutical formulations according to the matrix features. Quality criteria were applied to facilitate its transferability to testing laboratories. Fluoxetine was used therapeutically as the racemate, although a stereospecificity associated with its interactions with the neuronal serotonin-uptake carrier was demonstrated.

Electrokinetic chromatographic estimation of the enantioselective binding of nomifensine to human serum albumin and total plasma proteins.

This report is the first evidence of enantioselective binding of nomifensine to human serum albumin (HSA) and plasma proteins. The overall process with HSA included: (i) consistent experimental design along two independent sessions; (ii) incubation of nomifensine-HSA designed mixtures; (iii) ultrafiltration for separating the unbound enantiomers fraction; (iv) electrokinetic chromatography (EKC) using heptakis-2,3,6-tri-O-methyl-β-cyclodextrin as chiral selector to provide experimental data for enantiomers (first, E1, and second, E2, eluted ones); and (v) a recent direct equation allowing univariate tests and robust statistics to provide consistent parameters and uncertainty. A significant enantioselectivity to HSA (2.

Connecting simulated, bioanalytical, and molecular docking data on the stereoselective binding of (±)-catechin to human serum albumin.

The stereoselective binding of the frequently ingested nutraceutical (±)-catechin, with demonstrated differential biological activity between enantiomers, to human serum albumin (HSA), with the largest complexation and enantioselectivity potential among the plasmatic proteins, is studied by combining simulations to optimize the experimental design, robust in vitro electrokinetic chromatographic data, and molecular docking-chiral recognition estimates. Methodological and mathematical drawbacks in previous reports on (±)-catechin-HSA are detected and eliminated. Recent and novel direct equations extracted from the classical interaction model allows advantageous univariate mathematical data treatment, providing the first evidence of quantitative (±)-catechin-HSA enantioselectivity.

On the zopiclone enantioselective binding to human albumin and plasma proteins. An electrokinetic chromatography approach.

In this work, a methodology for the chiral separation of zopiclone (ZPC) by electrokinetic chromatography (EKC) using carboxymethylated-β-cyclodextrin as chiral selector has been developed and applied to the evaluation of the enantioselective binding of ZPC enantiomers to HSA and total plasma proteins. Two mathematical approaches were used to estimate protein binding (PB), affinity constants (K(1)) and enantioselectivity (ES) for both enantiomers of ZPC. Contradictory results in the literature, mainly related to plasma protein binding reported data, suggest that this is an unresolved matter and that more information is needed.

Evaluation of enantioselective binding of fluoxetine to human serum albumin by ultrafiltration and CE--experimental design and quality considerations.

Several pharmacokinetic processes are affected by enantioselectivity (ES). At the level of distribution, protein binding (PB) is one of the most important. The enantioselective binding of fluoxetine (FLX) to HSA has been evaluated in this work by ultrafiltration of FLX–HSA mixtures and chiral analysis of unbound fractions by EKC-CD.