7 research outputs found
Response surface methodology for the determination of the design space of enantiomeric separations on cinchona-based zwitterionic chiral stationary phases by high performance liquid chromatography
No full textChiral Capillary Electrokinetic Chromatography: Principle and Applications, Detection and Identification, Design of Experiment, and Exploration of Chiral Recognition Using Molecular Modeling
No full textThis work reviews the literature of chiral capillary electrokinetic chromatography from January 2016 to March 2021. This is done to explore the state-of-the-art approach and recent developments carried out in this field. The separation principle of the technique is described and supported with simple graphical illustrations, showing migration under normal and reversed polarity modes of the separation voltage. The most relevant applications of the technique for enantioseparation of drugs and other enantiomeric molecules in different fields using chiral selectors in single, dual, or multiple systems are highlighted. Measures to improve the detection sensitivity of chiral capillary electrokinetic chromatography with UV detector are discussed, and the alternative aspects are explored, besides special emphases to hyphenation compatibility to mass spectrometry. Partial filling and counter migration techniques are described. Indirect identification of the separated enantiomers and the determination of enantiomeric migration order are mentioned. The application of Quality by Design principles to facilitate method development, optimization, and validation is presented. The elucidation and explanation of chiral recognition in molecular bases are discussed with special focus on the role of molecular modeling
Determination of Capecitabine and Its Metabolites in Plasma of Egyptian Colorectal Cancer Patients
No full textThe incidence of colorectal cancer (CRC) is increasing worldwide. It has variable signs and symptoms starting from changes in bowel habit to nausea and vomiting. Chemotherapeutic agents are often prescribed in CRC such as Capecitabine (CCB) and 5-Fluorouracil (FU). CCB is the prodrug of FU in oral dosage form, which makes it preferable by physicians, since no hospitalization is needed for drug administration. CCB is activated to FU in a three-step reaction producing 5′-deoxy-5-fluorocytidine (DFCR) (by carboxylesterase (CES) enzyme), then 5′-deoxy-5-fluorouridine (DFUR) (by cytidine deaminase (CDD) enzyme) and finally FU (by thymidine phosphorylase (TP) enzyme), the active form, which is later deactivated to give 5,6-dihydro-5-fluorouracil (DHFU). Different patients exhibit variable drug responses and adverse in response to CCB therapy, despite being treated by the same dose, which could be attributed to the occurrence of different possible enzyme single nucleotide polymorphisms (SNPs) along the activation and deactivation pathways of CCB. The most commonly occurring toxicities in CCB therapy are hand-foot syndrome and diarrhea. This study aims at developing and validating a new method for the simultaneous determination of CCB and its metabolites by HPLC-UV, followed by a correlation study with the toxicities occurring during therapy, where predictions of toxicity could be based on metabolites’ levels instead of the tedious process of genotyping. A new superior analytical method was optimized by a quality-by-design approach using DryLab® 2000 software achieving a baseline resolution of the six analytes within the least possible gradient time of 10 min. The method also showed linearity (in a range from 1 to 500 μg/mL), accuracy, precision and robustness upon validation: The LOD was found to be 3.0 ng/mL for DHFU and CCB, and 0.3 ng/mL for DFUR, DFCR and FU. The LOQ was found to be 10.0 ng/mL for DHFU and CCB, and 1.0 ng/mL for DFUR, DFCR and FU. The clinical results showed a positive correlation between the concentration of DFCR and mucositis and between the concentration of DFUR and hand-foot syndrome, confirming that this technique could be used for predicting such toxicities
Chiral Monolithic Silica-Based HPLC Columns for Enantiomeric Separation and Determination: Functionalization of Chiral Selector and Recognition of Selector-Selectand Interaction
No full textThis review draws attention to the use of chiral monolithic silica HPLC columns for the enantiomeric separation and determination of chiral compounds. Properties and advantages of monolithic silica HPLC columns are also highlighted in comparison to conventional particle-packed, fused-core, and sub-2-µm HPLC columns. Nano-LC capillary monolithic silica columns as well as polymeric-based and hybrid-based monolithic columns are also demonstrated to show good enantioresolution abilities. Methods for introducing the chiral selector into the monolithic silica column in the form of mobile phase additive, by encapsulation and surface coating, or by covalent functionalization are described. The application of molecular modeling methods to elucidate the selector–selectand interaction is discussed. An application for enantiomeric impurity determination is also considered
Chiral Monolithic Silica-Based HPLC Columns for Enantiomeric Separation and Determination: Functionalization of Chiral Selector and Recognition of Selector-Selectand Interaction
No full textThis research received no external funding.This review draws attention to the use of chiral monolithic silica HPLC columns for the enantiomeric separation and determination of chiral compounds. Properties and advantages of monolithic silica HPLC columns are also highlighted in comparison to conventional particle-packed, fused-core, and sub-2- m HPLC columns. Nano-LC capillary monolithic silica columns as well
as polymeric-based and hybrid-based monolithic columns are also demonstrated to show good enantioresolution abilities. Methods for introducing the chiral selector into the monolithic silica column in the form of mobile phase additive, by encapsulation and surface coating, or by covalent functionalization are described. The application of molecular modeling methods to elucidate the selector–selectand interaction is discussed. An application for enantiomeric impurity determination is also considered
MiR-29a promotes lipid droplet and triglyceride formation in HCV infection by inducing expression of SREBP-1c and CAV1
No full textPediatric asthma comorbidities: Global impact and unmet needs
No full textReal-world data on the range and impact of comorbid health conditions that affect pediatric asthma are scant, especially from developing countries. Lack of data hinders effective diagnosis, treatment, and overall management of these complex cases. We, hereby, describe the common pediatric asthma comorbid conditions in terms of evidence for association, potential mechanisms of impact on asthma control, and treatment benefit. Obesity, upper airway allergies, dysfunctional breathing, multiple sensitizations, depressive disorders, food allergy, and gastro-esophageal reflux are common associations with difficult-to-treat asthma. On the other hand, asthma symptoms and/or management may negatively impact the well-being of children through drug adverse effects, worsening of anaphylaxis symptoms, and disturbing mental health. Awareness of these ailments may be crucial for designing the optimum care for each asthmatic child individually and may ultimately improve the quality of life of patients and their families. A multidisciplinary team of physicians is required to identify and manage such comorbidities aiming to mitigate the over-use of asthma pharmacotherapy. Asthma research should target relevant real-world difficulties encountered at clinical practice and focus on interventions that would mitigate the impact of such comorbidities. Finally, policymakers and global healthcare organizations are urged to recognize pediatric asthma control as a healthcare priority and allocate resources for research and clinical interventions. In other words, global asthma control needs support by compassionate scientific partnership. © 2024 The Author
