Chemometrically-aided general approach to novel adsorbents studies: Case study on the adsorption of pharmaceuticals by the carbonized leaves.

A chemometrically based approach was applied to select the most efficient drug adsorbent among the biochars obtained from the novel feedstock, the leaves of the invasive plant (). The representative target adsorbates (atenolol, paracetamol, ketorolac and tetracycline) were selected on the basis of their physicochemical properties to cover a wide chemical space, which is the usual analytical challenge. Their adsorption was investigated using design of experiments as a comprehensive approach to optimise the performance of the adsorption system, rationalise the procedure and overcome common drawbacks.

Development of Analytical Quality by Design Compliant Chaotropic Chromatography Method for Ziprasidone and Its Five Impurities Determination.

In this study, an AQbD-compliant chaotropic chromatography method for ziprasidone and the determination of its five impurities was developed. The influence of critical method parameters (initial and final methanol fraction in the mobile phase, gradient duration) on the set of selected critical method attributes (, , and ) was studied by Box-Behnken design. The errors resulting from the calculation of the model coefficients were propagated to the selected responses by Monte Carlo simulations, and their predictive distribution was obtained.

Analytical method development supported by DoE-DS approach for enantioseparation of (S,S)- and (R,R)-moxifloxacin.

In this paper, method for enantiomeric purity testing of fourth-generation fluoroquinolone, moxifloxacin hydrochloride, was developed and validated. Exceptional enantioselectivity for this assay was achieved using cyclodextrin type Chiral Stationary Phase (CSP), phenylcarbamate-β-cyclodextrin CSP, and mobile phase consisted of acetonitrile and triethylammonium acetate (TEAA) buffer. Analytical Quality by Design (AQbD) methodology, comprising Design of Experiments (DoE) - Design Space (DS) approach, was used for method development.

Determination of Bupropion and Its Impurities via a Chaotropic Chromatography Method Following Analytical Quality-by-Design Principles for Method Development.

A novel chaotropic chromatography method for the quantitative determination of bupropion and its impurities, following analytical quality-by-design (AQbD) principles, is presented. The analytical target profile (ATP) was defined on the basis of the efficient separation and reliable determination of bupropion and its five impurities in tablets. Preliminary experiments revealed the need for the addition of a gradient elution part.

Evaluation of chitosan/xanthan gum polyelectrolyte complexes potential for pH-dependent oral delivery of escin.

Escin is an amphiphilic and weakly acidic drug that oral administration may lead to the irritation of gastric mucosa. The entrapment of escin into chitosan (CH)/xanthan gum (XG)-based polyelectrolyte complexes (PECs) can facilitate controlled drug release which may be beneficial for the reduction of its side effects. This study aimed to investigate the influence of escin content and drying method on the formation, physicochemical, and controlled, pH-dependent drug release properties of CH/XG-based PECs.

Quantification of Zonisamide in Dried Blood Spots and Dried Plasma Spots by UPLC-MS/MS: Application to Clinical Practice.

In this research, a UHPLC-MS/MS method was developed and validated for the determination of zonisamide in dried plasma spots (DPS) and dried blood spots (DBS). Detection of zonisamide and internal standard, 1-(2,3-dichlorphenyl)piperazine, was carried out in ESI+ mode by monitoring two MRM transitions per analyte. Total run time, less than 2.

Chitosan/Sodium Dodecyl Sulfate Complexes for Microencapsulation of Vitamin E and Its Release Profile-Understanding the Effect of Anionic Surfactant.

Microencapsulation of bioactive substances is a common strategy for their protection and release rate control. The use of chitosan (Ch) is particularly promising due to its abundance, biocompatibility, and interaction with anionic surfactants to form complexes of different characteristics with relevance for use in microcapsule wall design. In this study, Ch/sodium dodecyl sulfate (SDS) microcapsules, without and with cross-linking agent (formaldehyde (FA) or glutaraldehyde (GA)), were obtained by the spray drying of vitamin E loaded oil-in-water emulsion.

Generic approach in a gradient elution HPLC method development that enables troubleshooting free method transfer.

Nowadays, method development is strongly focused on reducing time needed for method development and execution. This subject specially concerns gradient elution methods regarding the usual need for troubleshooting assistance with uncertain outcome during the method transfer from one laboratory to another. One of the main reasons for this situation is the dwell volume difference between HPLC systems.

Effect of ibuprofen entrapment procedure on physicochemical and controlled drug release performances of chitosan/xanthan gum polyelectrolyte complexes.

The effect of the entrapment procedure of a poorly water soluble drug (ibuprofen) on physicochemical and drug release performances of chitosan/xanthan polyelectrolyte complexes (PECs) was investigated to achieve controlled drug release as the ultimate goal. The formation of PECs for two drug entrapment procedures (before or after the mixing of polymers) at pH 4.6 and 5.

Corona Charged Aerosol Detector in studying retention and β-cyclodextrin complex stability using RP-HPLC.

Binding between cyclodextrin (CD) cavity and guest molecule in Reversed Phase High-Performance Liquid Chromatography (RP-HPLC) is dynamic process. In general, increasing CD concentration is inducing inclusion complex formation, leading to reduction of analyte's retention time. Consequently, the shortness in retention time is a measure of complex stability in HPLC.

Quantitative structure retention relationship modeling as potential tool in chromatographic determination of stability constants and thermodynamic parameters of β-cyclodextrin complexation process.

When cyclodextrins (CDs) are used in chromatography analytes' retention time is decreased with an increase in concentration of CD in the mobile phase. Thus complex stability constants can be determined from the change in retention time of the ligand molecule upon complexation. Since the preceding approach implies extensive and time-consuming HPLC experiments, the goal of this research was to investigate the possibility of using in silico prediction tools instead.

Analytical quality by design development of an ecologically acceptable enantioselective HPLC method for timolol maleate enantiomeric purity testing on ovomucoid chiral stationary phase.

Official method in Ph. Eur. for evaluation of timolol enantiomeric purity is normal-phase high performance liquid chromatography (NP-HPLC) method.

Hematocrit effect on dried blood spots in adults: a computational study and theoretical considerations.

Dried blood spots (DBS) are formed by deposition of a small amount of blood on specific adsorbent paper and its physical drying. DBS are employed as a sampling method in several fields of life sciences and drug research. A concern about DBS is the so-called 'Hematocrit (Ht) effect', as a different Ht leads, due to different viscosity, to different spot size, affecting assay bias.

Characterization of bonded stationary phase performance as a function of qualitative and quantitative chromatographic factors in chaotropic chromatography with risperidone and its impurities as model substances.

Numerous stationary phases have been developed with the aim to provide desired performances during chromatographic analysis of the basic solutes in their protonated form. In this work, the procedure for the characterization of bonded stationary phase performance, when both qualitative and quantitative chromatographic factors were varied in chaotropic chromatography, was proposed. Risperidone and its three impurities were selected as model substances, while acetonitrile content in the mobile phase (20-30%), the pH of the aqueous phase (3.

Analysis of potential genotoxic impurities in rabeprazole active pharmaceutical ingredient via Liquid Chromatography-tandem Mass Spectrometry, following quality-by-design principles for method development.

A novel Liquid Chromatography-tandem mass spectrometry (LC-MS/MS) method is presented for the quantitative determination of two potential genotoxic impurities (PGIs) in rabeprazole active pharmaceutical ingredient (API). In order to overcome the analytical challenges in the trace analysis of PGIs, a development procedure supported by Quality-by-Design (QbD) principles was evaluated. The efficient separation between rabeprazole and the two PGIs in the shortest analysis time was set as the defined analytical target profile (ATP) and to this purpose utilization of a switching valve allowed the flow to be sent to waste when rabeprazole was eluted.

Chemometrically assisted development and validation of LC-MS/MS method for the analysis of potential genotoxic impurities in meropenem active pharmaceutical ingredient.

A sensitive Liquid Chromatography tandem mass spectrometry (LC-MS/MS) method was developed and validated for the quantitative analysis of three potential genotoxic impurities (318BP, M9, S5) in meropenem Active Pharmaceutical Ingredient (API). Due to the requirement for LOD values in ppb range, a high concentration of meropenem API (30mg/mL) had to be injected. Therefore, efficient determination of meropenem from its impurities became a critical aim of this study, in order to divert meropenem to waste, via a switching valve.

Influence of the mobile phase and molecular structure parameters on the retention behavior of protonated basic solutes in chaotropic chromatography.

In this study, we present novel insights into the pH-dependent retention behavior of protonated basic solutes in chaotropic chromatography. To this end, two sets of experiments were performed to distinguish between mobile phase pH and ionic strength effects. In the first set, the ionic strength (I) was varied with the concentration of NaPF and additives that adjusted the mobile phase pH, while in the second set, I was kept constant by adding the appropriate amount of NaCl.

Quantitation of brinzolamide in dried blood spots by a novel LC-QTOF-MS/MS method.

In the current study, a rapid and sensitive LC-QTOF-MS/MS method for the determination of brinzolamide in dried blood spots (DBS) was developed and validated. This novel sample collection, storage and transfer technique was suitable for analyzing a drug with high distribution into red blood cells and negligible plasma levels. The method included an isocratic mobile phase consisting of methanol and 10mM ammonium formate (90:10, v/v) and detection in positive electrospray mode (ESI+).

Investigation into the phenomena affecting the retention behavior of basic analytes in chaotropic chromatography: Joint effects of the most relevant chromatographic factors and analytes' molecular properties.

The aim of this study was to systematically investigate the phenomena affecting the retention behavior of structurally diverse basic drugs in ion-interaction chromatographic systems with chaotropic additives. To this end, the influence of three factors was studied: pH value of the aqueous phase, concentration of sodium hexafluorophosphate, and content of acetonitrile in the mobile phase. Mobile phase pH was found to affect the thermodynamic equilibria in the studied system beyond its effects on the analytes' ionization state.

Development of liquid chromatographic method for the analysis of dabigatran etexilate mesilate and its ten impurities supported by quality-by-design methodology.

In this paper, the development of reversed-phase liquid chromatographic method for the analysis of dabigatran etexilate mesilate and its ten impurities supported by quality by design (QbD) approach is presented. The defined analytical target profile (ATP) was the efficient baseline separation and the accurate determination of the investigated analytes. The selected critical quality attributes (CQAs) were the separation criterions between the critical peak pairs because the mixture complexity imposed a gradient elution mode.

Quantitation of pregabalin in dried blood spots and dried plasma spots by validated LC-MS/MS methods.

In this paper, novel LC-MS/MS methods for the determination of antiepileptic drug pregabalin in dried matrix spots (DMS) are presented. This attractive technique of sample collection in micro amount was utilized in the form of dried blood spots (DBS) and dried plasma spots (DPS). Following a pre-column derivatization procedure, using n-propyl chloroformate in the presence of n-propanol, and consecutive liquid-liquid extraction, derivatized pregabalin and its internal standard, 4-aminocyclohexanecarboxylic acid, were detected in positive ion mode by applying two SRM transitions per analyte.

The influence of salt chaotropicity, column hydrophobicity and analytes' molecular properties on the retention of pramipexole and its impurities.

The aim of this study was to examine the interaction of the chaotropic salts of different position in Hofmeister series (CF3COONa, NaClO4, NaPF6) added to the mobile phase with the stationary phases of different hydrophobicity (C8 and C18 XTerra(®) columns), as well as their common influence on the retention behavior of pramipexole and its structurally related impurities. The extended thermodynamic approach enabled the understanding of the underlying separation mechanism. Comparing six different column-salt systems it was observed that general system hydrophobicity presented by salt chaotropicity and column hydrophobicity favors stationary phase ion-pairing over the ion-pair formation in the eluent.

Chaotropic salts in liquid chromatographic method development for the determination of pramipexole and its impurities following quality-by-design principles.

The aim of this paper is to present a development of liquid chromatographic method when chaotropic salts are used as mobile phase additives following the QbD principles. The effect of critical process parameters (column chemistry, salt nature and concentration, acetonitrile content and column temperature) on the critical quality attributes (retention of the first and last eluting peak and separation of the critical peak pairs) was studied applying the design of experiments-design space methodology (DoE-DS). D-optimal design is chosen in order to simultaneously examine both categorical and numerical factors in minimal number of experiments.

Vigabatrin in dried plasma spots: validation of a novel LC-MS/MS method and application to clinical practice.

This paper presents a LC-MS/MS method for the determination of antiepileptic drug vigabatrin in dried plasma spots (DPS). Due to its zwitterionic chemical structure, a pre-column derivatization procedure was performed, aiming to yield enhanced ionization efficiency and improved chromatographic behaviour. Propyl chloroformate, in the presence of propanol, was selected as the best derivatization reagent, providing a strong signal along with reasonable run time.

Testing the capability of a polynomial-modified gaussian model in the description and simulation of chromatographic peaks of amlodipine and its impurity in ion-interaction chromatography.

In this paper, the capability of a polynomial-modified Gaussian model to relate the peak shape of basic analytes, amlodipine, and its impurity A, with the change of chromatographic conditions was tested. For the accurate simulation of real chromatographic peaks the authors proposed the three-step procedure based on indirect modeling of peak width at 10% of peak height (W0.1), individual values of left-half width (A) and right-half width (B), number of theoretical plates (N), and tailing factor (Tf).