Search Results (230)

Background: Compound lipophilicity is a fundamental physicochemical property for determining the pharmacokinetic and pharmacodynamic profiles of therapeutic substances. It is successfully used in the early stages of drug candidates’ design and development. Aim: Taking into account the importance of this parameter, we aimed to assess and compare the utility of a hybrid procedure based on calculation methods and an experimental one for rapid and simple estimation of the lipophilicity of selected neuroleptics such as fluphenazine, triflupromazine, trifluoperazine, flupentixol and zuclopenthixol and their potential new derivatives. Methods: Log P values of the studied compounds were predicted by means of different platforms and algorithms: AlogPs, ilogP, XlogP3, WlogP, MlogP, milogP, logPsilicos-it, logP_consensus, logP_chemaxon and logP_ACD/Labs. The experimental determination of lipophilicity was carried out by reverse-phase thin-layer chromatography (RP-TLC) using three types of stationary phases—RP-2F₂₅₄, RP-8F₂₅₄ and RP-18F₂₅₄—and mobile phases consisted of acetone, acetonitrile and 1,4-dioxane as organic modifiers. Results: Our results provide a confident proposal of optimal chromatographic conditions to experimentally determine the lipophilicity of neuroleptic drugs, including new derivatives. Conclusions: Additionally, for the first time, the paper shows the application of selected topological indices in determining lipophilicity factors and other ADMET parameters of neuroleptics and, in the future, the newly synthesized quinoline derivatives of the studied compounds. Full article

Olive leaves, the main byproducts of olive cultivation, are characterized by a plethora of bioactive metabolites with significant nutritional value. Their main pentacyclic triterpenes, Oleanolic Acid (OA) and Maslinic Acid (MA), are two high added-value compounds with remarkable activities. This study aimed to develop an efficient methodology for extracting and purifying OA and MA, utilizing Supercritical Fluid Extraction (SFE) and Centrifugal Partition Chromatography (CPC)—two modern, scalable, and green techniques. A total of 21 g of olive leaves were subjected to SFE using supercritical CO₂ and ethanol as co-solvent. The extraction employed a step gradient mode, starting with 100% CO₂ and incrementally increasing ethanol (0–10% w/w) every 20 min. Fractions rich in OA and MA (500 mg) were further purified via CPC, utilizing pH zone refining to exploit the protonation and deprotonation properties of acidic triterpenes. The biphasic solvent system consisted of n-hexane, ethyl acetate, ethanol, and water (8:2:5:5 v/v/v/v), with trifluoroacetic acid added to the stationary phase and triethylamine added to the mobile phase. This two-step process yielded 89.5 mg of OA and 28.5 mg of MA with over 95% purity, as confirmed by HPLC-ELSD and ¹H-NMR. Moreover, purified compounds and SFE fractions exhibited promising elastase and collagenase inhibition, highlighting them as dermocosmetic agents. Full article

β-carotene, a high-value carotenoid widely used in the food, pharmaceutical, and cosmetics industries, is naturally synthesized by the microalga Dunaliella sp. However, the efficient extraction and purification of β-carotene from microalgae biomass remain a technical challenge. This study presents the development of a scalable and efficient isolation method employing high-performance countercurrent chromatography (HPCCC) to recover β-carotene from Dunaliella sp. The separation process was optimized by integrating two elution strategies (reverse phase and extrusion) using a biphasic solvent system of n-heptane and methanol (1:1, v/v). The upper phase served as the stationary phase, while the lower phase was used as the mobile phase. Two consecutive injections of 800 mg of microalgal extract each resulted in the isolation of 225.4 mg of β-carotene with a purity of 97% and a recovery of 98%. The developed HPCCC approach represents an efficient method for β-carotene purification and serves as a promising model for future scale-up in microalgae-based production platforms. Full article

The antihypertensive drugs indapamide, atenolol, metoprolol, propranolol and bisoprolol were considered in this research. Because they have structures that are affected by pH, developing a chromatographic method was challenging. Based on the speciation diagram of these compounds versus pH scale, a mixed-mode stationary phase (hydrophobic stationary phase, C18 and strong cation exchanger (SCX)) was our first choice. Design of Experiments (DoE) was used to estimate how various factors such as pH, mobile phase composition and flow rate influenced chromatographic performance. As a result, the separation was achieved in 24 min using an aqueous phosphate buffer phase (pH 7.20) and 20 mM triethylamine, with methanol being used as organic modifier (30%). Their retention mechanism was investigated. The new method was validated in term of linearity, limits of detection and quantification, precision, accuracy, and robustness. The method was applied to river water samples, and good results were obtained. Full article

The evaluation of the time spent by a solute exclusively in the mobile phase (dead time) is of fundamental interest for the interpretation of the retention data and obtainment of thermodynamic parameters for the HPLC process. This parameter depends on the volume occupied by the mobile phase and on the volume of the effective stationary phase from the HPLC column, and the measurement of these volumes poses a real challenge. This review discusses the evaluation of volumes of various phases involved in the retention process of solutes, which are related to the dead time, and the phase ratio for the separation. This paper attempts to cover as many points of view as possible regarding this topic in liquid chromatography, which is of importance for almost all separation mechanisms. Full article

Objectives: A simple method for quantifying fluconazole in small blood volumes has been developed using volumetric absorptive microsampling (VAMS^®) technology and isocratic high-performance liquid chromatography (HPLC) with ultraviolet (UV) detection. Methods: For sample collection, Mitra^® devices are used to keep the sample volume at 10 µL. For the quantitative determination of fluconazole, the Mitra^® samples are extracted using acetonitrile as the extraction agent, containing 2-(4-chlorophenyl)-1,3-bis(1,2,4-triazol-1-yl)propan-2-ol as the internal standard. A Synergi 4 μm Polar-RP 80 Å (150 × 2 mm) column forms the stationary phase, and a mixture of acetonitrile and phosphate buffer is the mobile phase. The UV detection is set at a wavelength of 210 nm. The therapeutic concentration range of 5 to 160 mg/L is covered, and the linear equation with 1/x² weighting is used to determine unknown samples. This method has been validated according to the current EMA and FDA guidelines for bioanalytical methods. Results: The validation data obtained after analysing whole blood samples (EDTA) showed within- and between-run accuracy between 94.4% and 115% and precision between 0.4% and 9.4%, respectively. A lower limit of quantification (LLOQ) of 5 mg/L was sufficient for therapeutic drug monitoring in paediatric patients receiving fluconazole as antifungal prophylaxis after haematopoietic cell transplantation. Conclusions: So far, 211 samples from 49 patients were successfully analysed, and concentrations between 5.84 mg/L and 107 mg/L were determined for whole blood Mitra^® samples. To our knowledge, this is the first application of VAMS^® technology using simple and cheap HPLC-UV quantification. Full article

Novel peptides based on common amino acid building blocks may serve as possible drug candidates; however, their flexible structures may require stabilization via the incorporation of conformational constraints. The insertion of unusual amino acids is a feasible option that may provide improved pharmacokinetic and pharmacodynamic properties of such peptide-type drugs. The stereochemical purity of these kinds of building blocks must be verified by an efficient separation technique, such as high-performance liquid chromatography. Here, we present and discuss the results of the stereoselective separation mechanism of ß-methylated phenylalanine (ß-MePhe), tyrosine (ß-MeTyr), 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid (ß-MeTic), and cyclohexylalanine (ß-MeCha) together with non-methylated Phe, Tyr, Tic, and Cha applying Cinchona alkaloid-based chiral stationary phases (CSPs). The studied zwitterionic CSPs acting as ion exchangers provided optimal performance in the polar ionic mode when methanol or a mixture of methanol and acetonitrile was utilized as the mobile phase together with organic acid and base additives. It was found that the basicity of small amines applied as mobile phase additives did not directly influence the chromatographic ion exchange concept. However, the size of the amines and their concentration led to a reduced retention time following the principles of ion exchange chromatography. On the basis of a systematic study of the effects of the eluent composition on the chromatographic behavior, important structure–retention and enantioselectivity relationships could be revealed. Through a temperature study, it has become evident that the composition of the eluent and the structure of analytes markedly affect the thermodynamic properties. Full article

A study was conducted to search for the best separation of eighteen cannabinoids, the maximum number of cannabinoids that have been quantified so far, for potency testing of hemp-based products using liquid chromatography diode array detector (LC-DAD). The investigation utilized four column types, all sharing the same dimension (150 mm × 2.1 mm) and core–shell particle size (2.7 µm), but different stationary phases: dimethyl-octadecyl (Poroshell 120 EC-C18), diisobutyl-octadecyl (Raptor ARC-18), reverse phase (RP)-carbamate (Cortecs Shield RP-18), and RP-amide (Ascentis Express RP-Amide). The resolution of adjacent cannabinoids was kept close to 1.5 or higher, while the separation time was kept as short as possible. The fastest separation was achieved within 15.0 min using two sequential Raptor ARC-18 columns, with a mobile phase consisting of 75.0% acetonitrile and 25.0% aqueous solution of 0.03% formic acid and 0.5 mM ammonium formate at pH 2.97, at a flow rate of 0.5 mL/min. A slightly improved resolution of the eighteen cannabinoids was obtained within 18.5 min using two sequential Poroshell 120 EC-C18 columns under similar conditions, except for a mobile phase containing 77.5% acetonitrile and a reduced flow rate of 0.45 mL/min due to backpressure higher than 600 bars. Furthermore, a rapid 7.0 min separation was achieved for potency testing of hemp-based products by liquid chromatography electrospray ionization tandem mass spectrometry (LC-ESI/MS/MS) using a Cortecs Shield RP-18 column, with a mobile phase consisting of 70.0% acetonitrile and 30.0% aqueous solution of 0.01% formic acid and 1 mM ammonium formate at pH 3.38 at a flow rate of 0.5 mL/min. Full article

Di-isopropyl methyl phosphonate (DIMP) has no major commercial uses but is a by-product or a precursor in the synthesis of the nerve agent sarin (GB). Also, DIMP is utilized as a simulant compound for the chemical warfare agents sarin and soman in order to test and calibrate sensitive IMS instrumentation that warns against the deadly chemical weapons. DIMP was measured from 2 ppb_v (15 μg m⁻³) to 500 ppb_v in the air using a pocket-held ToF ion mobility spectrometer, model LCD-3.2E, with a non-radioactive ionization source and ammonia doping in positive ion mode. Excellent sensitivity (LoD of 0.24 ppb_v and LoQ of 0.80 ppb_v) was noticed; the linear response was up to 10 ppb_v, while saturation occurred at >500 ppb_v. DIMP identification by IMS relies on the formation of two distinct peaks: the monomer M·NH₄⁺, with a reduced ion mobility K₀ = 1.41 cm² V⁻¹ s⁻¹, and the dimer M₂·NH₄⁺, with K₀ = 1.04 cm² V⁻¹ s⁻¹ (where M is the DIMP molecule); positive reactant ions (Pos RIP) have K₀ = 2.31 cm² V⁻¹ s⁻¹. Quantification of DIMP at trace levels was also achieved by GC-MS over the concentration range of 1.5 to 150 μg mL⁻¹; using a capillary column (30 m × 0.25 mm × 0.25 μm) with a TG-5 SilMS stationary phase and temperature programming from 60 to 110 °C, DIMP retention time (RT) was ca. 8.5 min. The lowest amount of DIMP measured by GC-MS was 1.5 ng, with an LoD of 0.21 μg mL⁻¹ and an LoQ of 0.62 μg mL⁻¹ DIMP. Our results demonstrate that these methods provide robust tools for both on-site and off-site detection and quantification of DIMP at trace levels, a finding which has significant implications for forensic investigations of chemical agent use and for environmental monitoring of contamination by organophosphorus compounds. Full article

This paper presents the results of the study of the composite based on magnesium hydride with the addition of nanosized nickel powder, obtained by the method of an electric explosion of wires. The obtained MgH₂-EEWNi (20 wt.%) composite with the core-shell configuration demonstrated the development of a defect structure, which makes it possible to significantly reduce the hydrogen desorption temperature from 418 °C for pure magnesium hydride to 229 °C for hydride with the addition of nickel powder. In situ studies of the evolution of the defect structure using positron annihilation methods and diffraction methods made it possible to draw conclusions about the influence of the Mg₂NiH_0.3 and Mg₂NiH₄ phases on the sorption and desorption properties of the composite. The results obtained in this work can be used in the field of hydrogen energy in mobile or stationary hydrogen storage systems. Full article

In this work, two novel (-)-menthol-based hydrophobic natural eutectic solvents with vanillin and cinnamic acid were prepared and applied as extraction solvents. In this regard, 12 endocrine disruptors, including phenol, 2,4-dimethylphenol, 2,3,6-trimethylphenol, 4-tert-butylphenol, 4-sec-butylphenol, 4-tert-amylphenol, 4-n-hexylphenol, 4-tert-octylphenol, 4-n-heptylphenol, 4-n-octylphenol, and 4-n-nonylphenol and bisphenol A, were studied in a green tea drink. A temperature-controlled liquid–liquid microextraction was used as the extraction method, and nano-liquid chromatography–ultraviolet detection was used as the separation and determination system. Different parameters affecting the compatibility of the non-ionic eutectic solvents with water-polar organic solvent mixtures and chromatographic and detection systems were optimized, including injection/dilution solvent, injection mode, mobile phase composition, and step gradient. With the same purpose, two stationary phases were tested, including XBridge^® C₁₈ and a mixed-phase Cogent C₃₀-XBridge^® C₁₈. Finally, the greenness and blueness of the methodology were assessed to evaluate the environmental profile and usability of the procedure. Full article

Due to the rapid increase in the use of anti-aging cosmetic products, there is a need to develop valid analytical methods to control their quality. The present work deals with the development and validation of a new chromatographic method for the quantitative determination of five lipophilic components (resveratrol, ferulic acid, quercetin, retinol, and α-tocopherol), with anti-aging properties, in a cold cream (w/o). For the HPLC-UV separation of the active ingredients, an HS, Discovery^® Supelco (Supelco Inc., Bellefonte, PA, USA), C₁₈ column (25 cm × 4.6 mm), 5 μm (at 40 °C) was used as a stationary phase while a binary system of A: Acetonitrile with formic acid 0.2% and B: H₂O with formic acid 0.2%, in gradient elution (flow 1.5 mL·min⁻¹), was used as mobile. The analytical method was validated according to ICH guidelines Q2(R2), where linearity (r² ≥ 0.998), selectivity, precision (% recovery 97.1–101.9), and accuracy (%RSD < 2) were evaluated. The processing of the samples for the recovery of the five analytes from the cream was investigated by experimental design methodology and the cross D-optimal technique (% recovery 98.5–102.9, %RSD < 2%, n = 5). Finally, the same analysis was applied to study the transdermal penetration of the active ingredients incorporated in cold cream (over a period of 8 h). Their behavior was compared with the corresponding one in suspension using Franz cells in a vertical arrangement. The new method is considered reliable for the analysis of the anti-aging product. Full article

Xanthohumol, a prenylated chalcone in the flavonoid group, naturally occurs in many plants and exhibits antioxidant, anticancer, anti-inflammatory, antibacterial, and antiviral effects. The growing interest in xanthohumol due to its potential therapeutic properties has led to the increase in the pool of products available on the market. The novelty of this study is the proposal of a rapid and cost-effective procedure useful for performing quality control on products containing xanthohumol in the form of dietary supplements and cosmetics as well as testing their stability. For this purpose, the thin-layer chromatography method with densitometric detection was used, which was validated in accordance with ICH (International Conference on Harmonization) guidelines. The mobile phase was toluene, 1,4-dioxane, and glacial acetic acid (37:10:1.5 v/v/v), and TLC silica gel 60 F₂₅₄ plates were used as the stationary phase. The validation process assessed linearity, with a correlation coefficient (r) of 0.9987. The calculated LOD (limit of detection) and LOQ (limit of quantification) values were 3.82 and 11.57 ng/spot, respectively. Accuracy was evaluated by determining percentage recovery at three concentration levels (80, 100, and 120%), with an average recovery of 100% and RSD below 1%, confirming good accuracy. Precision was indicated by an RSD of less than 2.20%. The average content of xanthohumol in dietary supplements ranged from about 8 to 29% of the content declared by the manufacturers. The stability tests showed that XN decomposes most slowly in water (t_0.5 = 10.86 h) compared with acidic (t_0.5 = 10.80 h) and alkaline solutions (t_0.5 = 7.39 h), as well as in the presence of an oxidizing agent (t_0.5 = 18.38 h), at all tested temperatures, which is confirmed by the calculated kinetic parameters. In the tests of antioxidant capacity, xanthohumol shows significantly higher radical scavenging capacity than vitamin C in the entire range of analyzed concentrations (0.03–2.40 mmol/L). Full article

1-Hydroxy-N-phenylnaphthalene-2-carboxamide and a series of seventeen other carboxanilides in the anilide part of dichlorinated, trichlorinated, dibrominated, tribrominated, and chlorinated/brominated variants have recently been reported as biologically active compounds mainly with antibacterial, antimycobacterial, and anticancer effects. Since lipophilicity is one of the factors influencing the bioavailability (absorption, distribution, metabolism, and elimination), activity, and even toxicity of bioactive compounds, all the derivatives were investigated for their lipophilic and hydrophilic properties. All eighteen compounds were analyzed by reversed-phase high-performance liquid chromatography (RP-HPLC). The procedure was performed under isocratic conditions with methanol as the organic modifier in the mobile phase using an end-capped non-polar C18 stationary reversed-phase column. The lipophilicity values are expressed as the logarithm of the capacity factor k (for the mobile phase water/methanol) and the distribution coefficients D at pH values of 6.5 and 7.4 (for the mobile phase buffer/methanol), as well as the calculated values of log P/Clog P by various methods. 1-Hydroxy-N-(3,4,5-trichlorophenyl)naphtha- lene-2-carboxamide and N-(4-bromo-3-chlorophenyl)-1-hydroxynaphthalene-2-carboxamide are the most lipophilic compounds of the whole series; on the other hand, surprisingly, unsubstituted 1-hydroxy-N-phenylnaphthalene-2-carboxamide is not the least lipophilic derivative. The mutual correlations between the experimental and predicted lipophilicity values are low; in addition, there are large deviations in the cross-correlations between log k and log D, which are due to the presence of a free ionizable phenolic group in the molecule. Full article

Reversed-phase liquid chromatography (RPLC) relies on a non-polar stationary phase and a more polar hydro-organic mobile phase, where compound retention is primarily governed by hydrophobicity, with more hydrophobic compounds being retained longer. The introduction of secondary equilibria in the chromatographic system through additives, such as anionic surfactants and ionic liquids (ILs), was proposed to mitigate ionic interactions between positively charged analytes and the anionic free silanol groups in non-endcapped stationary phases, thereby preventing increased retention and peak tailing. Additionally, the combined hydrophobic and ionic interactions between cationic analytes and the ions in these additives was demonstrated to create mixed retention mechanisms that influence retention and selectivity. In this regard, this study investigates aqueous chromatographic systems incorporating both the anionic surfactant sodium dodecyl sulfate (SDS) and the IL 1-hexyl-3-methylimidazolium chloride as mobile phase reagents. This combination of reagents modulates the retention, eliminating the need for organic solvents and resulting in highly sustainable HPLC procedures. The chromatographic behavior was assessed using two different C18 columns (Zorbax Eclipse and XTerra-MS). The strength of solute interactions was estimated by calculating equilibrium parameters and the contributions of hydrophobic and ionic interactions through simple mathematical models. Focusing on the retention of six basic drugs (β-adrenoceptor antagonists), the study highlighted the significant role of ionic interactions. The results demonstrate the feasibility of using aqueous systems combining SDS and an IL for the efficient separation of moderately polar basic compounds without the use of organic solvents. Full article