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.

Modified Gaussian models applied to the description and deconvolution of peaks in chiral liquid chromatography.

The description of the profiles of chromatographic peaks has been studied extensively, with a large number of proposed mathematical functions. Among them, the accuracy achieved with modified Gaussian models that describe the deviation of an ideal Gaussian peak as a change in the peak variance or standard deviation over time, has been highlighted. These models are, in fact, a family of functions of different complexity with great flexibility to adjust chromatographic peaks over a wide range of asymmetries and shapes.

Prospective computational design and in vitro bio-analytical tests of new chemical entities as potential selective CYP17A1 lyase inhibitors.

The development and advancement of prostate cancer (PCa) into stage 4, where it metastasize, is a major problem mostly in elder males. The growth of PCa cells is stirred up by androgens and androgen receptor (AR). Therefore, therapeutic strategies such as blocking androgens synthesis and inhibiting AR binding have been explored in recent years.

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.

On-line monitoring of food fermentation processes using electronic noses and electronic tongues: a review.

Fermentation processes are often sensitive to even slight changes of conditions that may result in unacceptable end-product quality. Thus, close follow-up of this type of processes is critical for detecting unfavorable deviations as early as possible in order to save downtime, materials and resources. Nevertheless the use of traditional analytical techniques is often hindered by the need for expensive instrumentation and experienced operators and complex sample preparation.

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.

Experimental-like affinity constants and enantioselectivity estimates from flexible docking.

Experimental-like affinity constants and enantioselectivity estimates, not predicted so far computationally, were obtained using a novel flexible modeling/docking combined strategy. The S- and R-warfarin-human serum albumin (HSA, site I) complexes were used as an interaction model. The process for a verified estimation includes the following: (i) ionized open chain forming at physiological pH (a recent focus); (ii) conformational search (molecular mechanics and Monte Carlo methods); (iii) rigid protein-flexible ligand docking (GlideXP) generating low energy paired S- and R-poses; (iv) graphical comparison against the X-ray crystal structure (unsatisfactory verification step); (v) quantum polarized ligand docking (insufficient verification step); (vi) induced fit docking (one pose satisfying the verification criterion; selection step); (vii) converting docking scores to affinity and enantioselectivity estimates (log K(S) = 5.

Evaluation of enantioselective binding of propanocaine to human serum albumin by ultrafiltration and electrokinetic chromatography under intermediate precision conditions.

Stereoselectivity in protein binding can have a significant effect on the pharmacokinetic and pharmacodynamic properties of chiral drugs. In this paper, the enantioselective binding of propanocaine (PRO) enantiomers to human serum albumin (HSA), the most relevant plasmatic protein in view of stereoselectivity, has been evaluated by incubation and ultrafiltration of racemic PRO-HSA mixtures and chiral analysis of the bound and unbound fractions by electrokinetic chromatography using HSA as chiral selector. Experimental conditions for the separation of PRO enantiomers using HSA as chiral selector and electrokinetic chromatography have been optimised.