Current Analytical Chemistry - Volume 18, Issue 10, 2022

Timely and accurate evaluation of clinical parameters associated with endothelial dysfunction is critical in diagnosing and treating atherosclerosis, which represents a severe health problem, accounting for at least 30% of deaths globally. A critical early event in the pathogenesis of atherosclerosis is the oxidative modification of low-density lipoprotein (LDL). Oxidized LDL (OxLDL) represents numerous changes in lipid and apolipoprotein B (apo B) fractions of LDLs generated by lipid peroxidation. Another indicator of perturbed vascular homeostasis is homocysteine (Hcy), an amino acid containing sulfhydrylgroup, an intermediate methionine and cysteine biosynthesis product. The total level of Hcy in plasma correlates better than cholesterol with the risk of cardiovascular disease. In addition, nitric oxide (NO) plays an essential role in regulating vascular physiological homeostasis due to its involvement in intravascular free radical and oxidant reactions. Reduced NO decreases oxidative stress in the vascular wall, which reduces the rate of LDL oxidation and the expression of redox-sensitive genes involved in atherogenesis. Endothelial dysfunction is typically associated with increased levels of OxLDL, decreased nitric oxide (NO), and hyperhomocysteinemia. Thus, OxLDL, Hcy, and NO are representative parameters of oxidative stress and endothelial dysfunction. Considering the important role of oxLDL, Hcy and NO in oxidative stress, atherogenesis and accompanying endothelial dysfunction, the challenge of the present work was to systematically present available methods for reliable measurement of these parameters and assess their potential for the use in the clinical setting. Here we present a comprehensive overview of analytical methods for measuring OxLDL, HCy, and NO in biological samples and discuss their advantages and potential problems regarding their application in clinical settings.

Chirality seems to be a pivotal technique in the field of science. Research teams are quite well versed in empirical separation, however, at the same time, they are clueless about the evolution of chiral separation. As per the guidelines of the United States Food and Drug Administration (US FDA), chiral drugs must be unraveled before they are sold to the public. Stereogenic separation has gained prominence during the last 10 decades due to the disparate biological function of enantiomers in the stereogenic environment. Chiral drugs exhibit a wide range of bioavailability, distribution, and pharmacodynamic properties; concomitantly, they exert divergent pharmacological and toxicological properties. Enantiomeric chiral products could be considered safe and potent in combating various diseases, including metabolic diseases like diabetes. Several studies have delineated the development of a novel analytical and bioanalytical method to detect/segregate/quantify chiral chemical components in medicinal chemistry. The same physicochemical characteristics of enantiomers have been proven to be beneficial to the estrangement of stereogenic compounds. Furthermore, the advancement of bioanalytical methods is also critical to shedding light on the destiny of distinct enantiomers in the biological environment. HPLC (High-Performance Liquid Chromatography) and CE (Capillary Electrophoresis) have been the most commonly employed separation techniques. But the technical advances are required to enhance the efficiency of detection and quantification of chiral molecules on a large scale. With technical advances, the current review delineates the need for the chiral separation of stereogenic antidiabetic drug compounds. Furthermore, this research is focused on the enantioseparation of chiral antidiabetic drugs and a brief overview of the analytical and bioanalytical methods conducted on distant chiral antidiabetic drugs to improve the efficiency of chiral separation.

Background: The effluent release containing heavy metals, such as Cd (II) ions, poses drastic risks to both the natural environment and human health. In this research, a novel nano sorbent from the pyridine derivative was prepared for dispersive solid-phase extraction of Cd (II) ions. Methods: Graphene oxide (GrO) was chemically modified by a 2-aminopyridine group (2Ap) through a multistep procedure. The effect of adsorbent amount, pH, temperature, and equilibrium time on sorption of the Gr2Ap adsorbent was studied; Gr2Ap adsorbent displayed a high ability to adsorb Cd (II) at pH = 6. Furthermore, to inquire about the adsorption isotherms of metal ions sorption mechanism, the model of Freundlich and Langmuir was fitted to empirical isotherm data. Besides, in the inspection of the basic process of the metal sorption mechanism, pseudo-first and second-order kinetics and Roginsky-Zeldovich types were found to be compatible with adsorption kinetic results. Results: The concentration factor and limit of detection for Cd (II) were 12.5 and 1.84 μg/L, respectively. According to the value of the correlation coefficient factor, the Gr2Ap adsorbent exhibited the highest ability to adsorb Cd (II) ions (22.54 mg/g) at pH=6. The pseudo-second-order pattern of Cd (II) adsorption fit best with the kinetic result. Conclusion: The Gr2Ap exhibited a high potential for removing the heavy metal ions from aqueous samples. Besides, the current research showed the method to be efficient, easy, inexpensive, and apt for evaluating the Cd (II) ions in several samples of water and wastewater.

Background: In this study, trace copper plays an important role in plant growth and is a biological component of various enzymes involved in both photosynthesis and plant respiration. Objective: Electrochemical voltammetric bioassay of trace copper ion was detected using photo-sensing diode circuits (PSD) with working sensors for ppb levels trace detection in agricultural water by stripping and cyclic voltammetry. Results: Optimum voltammetric conditions were examined. The system used was simple and utilized inexpensive circuits of our fabricated systems; however, a low detection limit was attained at 40.0 ugL-¹. Conclusion: The developed technique can be used in determining trace amounts of copper, especially in agricultural water resources.

Background: Cymbopogon khasianus is a widely used industrial and pharmacologically important aromatic grass species. Objective: The present investigation was designed to study and compare the elemicin rich Cymbopogon khasianus essential oil (EREO), its pharmacological effects and genotoxicity with pure compound elemicin. Materials and Methods: Chemical composition identification was performed using GC/MS and NMR techniques. 2,2-diphenyl-1-picryl-hydrazyl-hydrate (DPPH), reducing power assay for antioxidant; albumin denaturation, a protease inhibitor for anti-inflammatory; acetylcholinesterase (AChE) for anticholinesterase; amylase inhibitory for anti-diabetic; tyrosine inhibitory for skin whitening; disc diffusion and minimum inhibitory concentration assay for antimicrobial, and Allium cepa assay for genotoxicity were used. Results: GC/MS analysis identified 38 compounds; among them, elemicin 72.34%, D-limonene 3.81%, and methyl eugenol 3.34% were the major compounds. A significant amount of antioxidant activity IC50 31.38 μg/mL; anti-inflammatory activity (protein denaturation assay) IC50 16.77 μg/mL; protease inihibitor assay IC50 51.08 μg/mL; anticholinesterase IC50 12.095 μg/mL; antidiabetic activity IC50 17.36 μg/mL; and anti-tyrosinase activity IC50 17.69 μg/mL were reported. Antimicrobial activity analysis against 13 microbial strains revealed negative effects. Genotoxicity study using Allium cepa assay revealed negative toxicity of EREO with an aberration percentage of 04.30% and pure elemicin 05.30%, which was very low in comparison to ethyl-methanesulfonate (EMS) 13.90%. Conclusion: To the best of our knowledge, this is the first scientific evaluation of novel elemicin rich EREO pharmacological properties compared with pure compound elemicin. Together, it can be stated that EREO possesses antioxidant, anti-inflammatory, and anti-cholinesterase activities way better than pure compound elemicin as well as standard drugs used.

Background: The affinity of a drug to the identified target (protein/enzyme) is a critical characteristic in the development of a novel drug. Fluoroquinolone derivatives with a carboxylic group change have improved antimicrobial and anticancer activity while maintaining antibacterial activity similar to parent drugs. Aim: In this paper, the rationale upon which synthesis of the new compounds is based, evaluation of their anticancer activity with in silico study, and suggestion of their mechanism of action are presented. Methods: Different practical procedures were used for the synthesis of four new gatifloxacin 3- carboxamide derivatives with their spectral data (UV-vis, IR, and 1H-NMR). The enantioseparation and docking studies are presented and discussed. Results: Four gatifloxacin 3-carboxamide derivatives were enantioseparated using a high-performance liquid chromatography approach using two distinct polysaccharide-based chiral stationary phases (CSPs). The baseline enantioseparation of all derivatives evaluated in this study was achieved using both coated and immobilized amylose columns. In silico molecular docking study revealed that all compounds showed good docking score. Conclusion: The novel fluoroquinolone caboxamides derivatives could be repositioned as DNA topoisomerase II inhibitors, allowing them to be employed as anticancer agents, according to our in silico study. However, in vitro and in vivo experiments are required to confirm their efficacy.

Aim: To develop a hot stage microscopy-based method for the determination of particle size in reverse engineering and establishment of a platform technology employing carvedilol as a model drug. It was hypothesized that reverse engineering using thermal methods would suggest a logical path in decoding the innovator’s formulation to develop an efficient generic product and preconize the morphology of an active pharmaceutical ingredient (API). Background: To develop a generic formulation, a detailed analysis of identification, quantification and characterization of APIs and excipients present in the innovator product is a mandatory requirement. Identification of actives, excipients, and manufacturing processes involved in innovator product formulation can be facilitated using reverse engineering studies. Objective: The objective of this study was to establish a platform technology for the determination of particle size in reverse engineering using hot stage microscopy (HSM). Methods: Differential scanning calorimetry (DSC) and HSM techniques were employed for the identification of different unit processes that can affect the particle size distribution of API during formulation. Results: DSC technique helped to unwind information about the qualitative as well as quantitative nature of the formulation blend. HSM technique helped to reveal the particulate level properties of the drug present in the blend and formulation. Conclusion: The study concluded that the two thermal techniques DSC and HSM, together could be effectively used to reverse engineer a given formulation using a very less sample quantity. The study suggested a logical path in decoding innovator’s formulation to develop an efficient generic product. Moreover, this HSM-based thermal method of particle size determination will offer new insight into the decoding of an innovator product in a shorter period.

Background: Zinc oxide nanoparticles (ZnO-NPs) have been shown to exert a non-negligible impact on the environment. Objective: Kaolin and humic acid were used in the aqueous environment to study their effects on the removal of ZnO-NPs. Methods: In this work, polyaluminum ferric chloride (PAFC)/cationic polyacrylamide (CPAM) coagulants were used together with kaolin and humic acid to study their effects on the removal of ZnO-NPs and analyze their mechanism of action. Results: The results showed that the removal rate of ZnO-NPs in the humic acid system decreased by about 30% compared to that in the pure water system, and increasing ionic strength and humic acid concentration were not conducive to removing ZnO-NPs. On the other hand, the ZnO-NPs removal rate in the kaolin system was up to 96.28%, and increasing ionic strength and kaolin concentration contributed to the removal of ZnO-NPs. In the humic acid and kaolin systems, the effects of coagulant dosage and pH on the removal of ZnO-NPs were about the same as in the pure water system. Moreover, 5 mg/L humic acid inhibited floc growth during removal of ZnO-NPs by coagulation with PAFC/CPAM. In contrast, 5 mg/L kaolin promoted flocs growth, resulting in stronger and more stable flocs and a 5.25% increase in the fractal dimension compared to the pure water system. Conclusion: These results suggested that suspended solids and natural organic matter in the water could directly affect the effectiveness of coagulation to remove ZnO-NPs.