Search Results (8)

A reversed-phase high-performance liquid chromatographic (HPLC) method was developed for the simultaneous determination of the potential impurities of dexketoprofen, including the distomer R-ketoprofen. After screening the separation capability of four polysaccharide columns (Lux Amylose-1, Lux Amylose-2, Lux Cellulose-1 and Lux Cellulose-2) in polar organic and in reversed-phase modes, appropriate enantioseparation was observed only on the Lux Amylose-2 column in an acidified acetonitrile/water mixture. A detailed investigation of the mobile phase composition and temperature for enantio- and chemoselectivity showed many unexpected observations. It was observed that both the resolution and the enantiomer elution order can be fine-tuned by varying the temperature and mobile phase composition. Moreover, hysteresis of the retention times and enantioselectivity was also observed in reversed-phase mode using methanol/water mixtures on amylose-type columns. This could indicate that the three-dimensional structure of the amylose column can change by transitioning from a polar organic to a reversed-phase mode, which affects the enantioseparation process. Temperature-dependent enantiomer elution order and rare enthalpic/entropic controlled enantioseparation in the operative temperature range were also observed in reversed-phase mode. To find the best methodological conditions for the determination of dexketoprofen impurities, a full factorial optimization design was performed. Using the optimized parameters (Lux Amylose-2 column with water/acetonitrile/acetic acid 50/50/0.1 (v/v/v) at a 1 mL/min flow rate at 20 °C), baseline separations were achieved between all compounds within 15 min. Our newly developed HPLC method was validated according to the current guidelines, and its application was tested on commercially available pharmaceutical formulations. According to the authors’ knowledge, this is the first study to report hysteretic behavior on polysaccharide columns in reversed-phase mode. Full article

Background: Translocator protein (TSPO) is a neuroinflammation hallmark. Different TSPO affinity compounds have been produced and over time, the techniques of radiolabeling have been refined. The aim of this systematic review is to summarize the development of new radiotracers for dementia and neuroinflammation imaging. Methods: An online search of the literature was conducted in the PubMed, Scopus, Medline, Cochrane Library, and Web of Science databases, selecting published studies from January 2004 to December 2022. The accepted studies considered the synthesis of TSPO tracers for nuclear medicine imaging in dementia and neuroinflammation. Results: A total of 50 articles was identified. Twelve papers were selected from the included studies’ bibliographies and 34 were excluded. Thus, 28 articles were ultimately selected for quality assessment. Conclusion: Huge efforts in developing specific and stable tracers for PET/SPECT imaging have been made. The long half-life of ¹⁸F makes this isotope a preferable choice to ¹¹C. An emerging limitation to this however is that neuroinflammation involves all of the brain which inhibits the possibility of detecting a slight inflammation status change in patients. A partial solution to this is using the cerebellum as a reference region and developing higher TSPO affinity tracers. Moreover, it is necessary to consider the presence of distomers and racemic compounds interfering with pharmacological tracers’ effects and increasing the noise ratio in images. Full article

Freshwater snails are intermediate hosts for several snail-borne diseases affecting humans and animals. Understanding the distribution of snail intermediate hosts and their infection status is very important to plan and implement effective disease prevention and control interventions. In this study, we determined the abundance, distribution, and trematode infection status of freshwater snails in two agro-ecological zones of Ethiopia. We sampled snails from 13 observation sites and examined them for trematode infections using a natural cercarial shedding method. A redundancy analysis (RDA) was used to examine the relationship between snail abundance and environmental variables. Overall, a total of 615 snails belonging to three species were identified. Lymnea natalensis and Bulinus globosus were the dominant snail species, representing 41% and 40% of the total collection, respectively. About one-third of the total snail population (33%) shed cercariae. The cercariae species recorded were Xiphidiocercaria, Brevifurcate apharyngeate distome (BAD), Echinostome, and Fasciola. Snail species were found in high abundance in aquatic habitats located in the agricultural landscape. Therefore, land-use planning and protection of aquatic habitats from uncontrolled human activities and pollution can be considered as important strategies to prevent and control the spread of snail-borne diseases in the region. Full article

Chirality is a major theme in the design, discovery, and development of new drugs. Historically, pharmaceuticals have been synthesized as racemic mixtures. However, the enantiomeric forms of drug molecules have distinct biological properties. One enantiomer may be responsible for the desired therapeutic effect (eutomer), whereas the other may be inactive, interfere with the therapeutic form, or exhibit toxicity (distomer). Classical chemical synthesis usually leads to a racemic mixture unless stereospecific synthesis is employed. To meet the requirements of single-enantiomeric drugs, asymmetric synthesis has evolved at the forefront of drug discovery. Asymmetric synthesis involves the conversion of an achiral starting material into a chiral product. This review emphasizes the methods used for synthesizing FDA-approved chiral drugs during 2016–2020, with a special focus on asymmetric synthesis by means of chiral induction, resolution, or chiral pool. Full article

A high-performance liquid chromatographic method was developed for the simultaneous determination of the related substances—three potential synthesis-related chemical impurities and the distomer—of escitalopram. The separation capacity of seven different polysaccharide-type chiral columns, including three amylose-based (Lux Amylose-1, Lux i-Amylose-1, Lux Amylose-2) and four cellulose-based columns (Lux Cellulose-1, Lux Cellulose-2, Lux Cellulose-3, and Lux Cellulose-4) were screened in the polar organic and reversed-phase modes. Lux Cellulose-1, based on cellulose tris(3,5-dimethylphenylcarbamate) as the chiral selector with an acetonitrile-water mixture containing 0.1% diethylamine was identified as the most promising separation system. Using the “one factor at a time” optimization approach, the effect of column temperature, flow rate, and mobile phase constituents on separation performance was evaluated, and the critical resolution values were determined. A U-shaped retention pattern was obtained when plotting the retention factors of the citalopram enantiomers versus the water content of the binary mobile phases on the Lux Cellulose-1 column. A thermodynamic analysis revealed enthalpy-driven enantioseparation in both the polar organic and reversed-phase modes. For further method optimizations, an L9 orthogonal array table was employed. Using the optimized parameters (Lux Cellulose-1 column with 0.1% (v/v) diethylamine in water/acetonitrile 55/45 (v/v); 0.8 mL/min flow rate at 25 °C), baseline separations were achieved between all compounds. Our newly developed HPLC method was validated according to the ICH guidelines and its application was tested with a commercially available pharmaceutical formulation. The method proved to be suitable for routine quality control of related substances and the enantiomeric purity of escitalopram. Full article

Chirality plays an important role in the development of many pharmaceuticals, being a general property of ‘handedness’; nevertheless, a large number of pharmaceuticals are still marketed and administered as racemates. Chirality is all around and even within us; indeed, receptors and enzymes are chiral entities and interact in a specific manner with chiral drugs. Consequently, controlling enantiomeric purity and isolating the enantiomers from chiral drugs remains a crucial subject for analytical, clinical, and regulatory purposes, thus, improving the drug safety profile. The classical examples of spontaneous enantiomerization and severe toxicity related to chirality are represented by ibuprofen and thalidomide, respectively, but numerous other cases have been reported in the literature. This review intends to offer a brief overview on the most common chiral drugs used in therapy for the treatment of various diseases. Full article

A novel, validated, reversed-phase (RP), chiral high performance liquid chromatography (HPLC) method was developed for the enantiopurity control analysis of naproxen, a frequently used non-steroidal anti-inflammatory agent using polysaccharide-type chiral stationary phase (CSP). In the screening phase of method development, seven columns were tested in polar organic (PO) mode using mobile phases consisting of 0.1% acetic acid in methanol, ethanol, 2-propanol, and acetonitrile. Enantiorecognition was observed only in five cases. The best enantioseparation was observed on a Lux Amylose-1 column with 0.1% (v/v) acetic acid in ethanol with a resolution (R_s) of 1.24. The enantiomer elution order was unfavorable, as the distomer eluted after the eutomer. When the ethanolic mobile phase was supplemented with water, enantiomer elution order reversal was observed, indicating a difference in the enantiorecognition mechanism upon switching from PO to RP mode. Furthermore, by changing ethanol to methanol, not only lower backpressure, but also higher resolution was obtained. Subsequent method optimization was performed using a face-centered central composite design (FCCD) to achieve higher chiral resolution in a shorter analysis time. Optimized parameters offering baseline separation were as follows: Lux Amylose-1 stationary phase, thermostated at 40 °C, and a mobile phase consisting of methanol:water:acetic acid 85:15:0.1 (v/v/v), delivered with 0.65 mL/min flow rate. Using these optimized parameters, a R_s = 3.21 ± 0.03 was achieved within seven minutes. The optimized method was validated according to the ICH guidelines and successfully applied for the analysis of different pharmaceutical preparations, such as film-coated tablets and gel, as well as fixed-dose combination tablets, containing both naproxen and esomeprazole. Full article

Complexes {Ag[NHC^Mes,R]}_n (R = H, 2a; Me, 2b and 2b’; ⁱPr, 2c; ⁱBu, 2d), were prepared by treatment of imidazolium precursor compounds [Im^Mes,R] (2-(3-mesityl-1H-imidazol-3-ium-1-yl)acetate, 1a, (S)-2-alkyl(3-mesityl-1H-imidazol-3-ium-1-yl)acetate, 1b–d, and (R)-2-methyl(3-mesityl-1H-imidazol-3-ium-1-yl)acetate, 1b’, with Ag₂O under appropriate conditions. They were characterised by analytical, spectroscopic (IR, ¹H, and ¹³C NMR and polarimetry), and X-ray methods (2a). In the solid state, 2a is a one-dimensional coordination polymer, in which the silver(I) cation is bonded to the carbene ligand and to the carboxylate group of a symmetry-related Ag[NHC^Mes,H] moiety. The coordination environment of the silver centre is well described by the DFT study of the dimeric model {Ag[NHC^Mes,H]}₂. The antimicrobial properties of these complexes were evaluated versus Gram-negative bacteria E. coli and P. aeruginosa. From the observed MIC and MBC values (minimal inhibitory concentration and minimal bactericidal concentration, respectively), complex 2b’ showed the best antimicrobial properties (eutomer), which were significantly better than those of its enantiomeric derivative 2b (distomer). Additionally, analysis of MIC and MBC values of 2a–d reveal a clear structure–antimicrobial effect relationship. Antimicrobial activity decreases when the steric properties of the R alkyl group in {Ag[NHC^Mes,R]}_n increase. Full article