Ulusoy S, İrem Altunbaş Ş, Gürbüzer A, Polat Ü, İbrahim Ulusoy H.
Analyst
PMID:41804642
Free PMC article
A highly selective and sensitive analytical strategy was established for the trace quantification of two oral antidiabetic drugs, gliclazide (GLZ) and glimepiride (GLM). The procedure integrates magnetic solid-phase extraction (MSPE) with high-performance liquid chromatography coupled to diode array detection (HPLC-DAD). In this approach, a newly engineered magnetic-aminopropyltriethoxysilane-sulfanilamide (Fe 3 O 4 @APTES-sulfanilamide) was synthesized and utilized as an innovative adsorbent. Sulfanilamide as a functional molecule on the surface has been used for the first time in this study. The hybrid structure, consisting of a Fe 3 O 4 magnetic core and a sulfanilamide-functionalized silane shell, provides strong binding affinity toward sulfonylurea compounds through synergistic hydrogen bonding and π-π interactions. Optimization studies were carried out to achieve the best extraction efficiency by adjusting experimental variables such as solution pH, adsorption and desorption times, and solvent composition. Under the final working conditions (pH 6.0; desorption with an acetonitrile-methanol mixture), both target analytes were effectively preconcentrated prior to chromatographic determination. Separation was accomplished using an isocratic elution system containing 10% methanol, 40% phosphate buffer (pH 3.0), and 50% acetonitrile, with UV detection at 219 and 256 nm. The developed protocol demonstrated excellent linearity, remarkable enrichment factors, and very low detection limits. Precision studies yielded RSD values below 3.5% ( n = 3, 100 ng mL -1 ). The reliability of the proposed method was further validated by its successful application to both synthetic and human urine samples, giving satisfactory recovery results. This newly designed Fe 3 O 4 @APTES-sulfanilamide -based MSPE coupled with HPLC-DAD provides a robust, time-efficient, and eco-friendly platform for the determination of trace oral antidiabetic drugs in complex biological matrices.
Albrethsen J, Andreasen JK, Anton J, Sennels HP, Jørgensen HL, Hannibal J, Hermann D, Wewer Albrechtsen NJ.
Scand J Clin Lab Invest
PMID:42008634
Free PMC article
Measurement of plasma melatonin is important in studies of sleep disorders and neurodegenerative diseases and is also increasingly associated with cardiometabolic diseases and cancer. There is currently an increase in the usage of melatonin in the population. However, commercially available and reliable melatonin assays are lacking. Here we present a rapid and simple LC-MS/MS-based method for plasma melatonin in a clinical laboratory. The method demonstrates a limit of detection of 5 ng/L and inter-assay imprecision p p < 0.03) but demonstrated a substantial bias. We conclude that our simple LC-MS/MS method can detect biologically relevant changes in plasma melatonin and may enable insight into circadian biology in humans. We propose that the observed differences between melatonin assays could be clarified by the distribution of reference plasma melatonin material and that additional studies are needed to fully understand the minimum circulating levels of melatonin in the daytime.
Fu Q, Johnson CWC, Inker LA, Van Eyk JE, CRIC Study Investigators.
J Proteome Res
PMID:42007652
Free PMC article
Robust and reproducible assays capable of specific and quantitative monitoring of multiple biologically important proteins, among the thousands of human plasma proteins, can be used to represent the overall health of an individual and distinguish health versus disease. In this study, we established an LC-MS assay to monitor a Health Surveillance Panel (HSP), comprising 60 circulating plasma proteins selected based on their biological functions and/or disease associations. Plasma samples were prepared for proteomic analysis in an automated process and analyzed using an optimized, scheduled LC-MRM assay composed of 60 endogenous proteins monitored by 364 transitions from 117 proteotypic peptides, along with their stable isotopically labeled standard peptides. For each proteotypic peptide, a quantifier ion and at least two qualifier ions were selected based on consistent peak area ratios, a linear response for the quantifier ion, and a low limit of quantification. As proof of concept, we evaluated the performance of our HSP assay in a case-control study of progressive chronic kidney disease (CKD). Reduced plasma concentrations of alpha-2-antiplasmin, antithrombin-III, and immunoglobulin heavy constant alpha 1 correlated with CKD, with p -values <0.05. These results demonstrate that CKD-associated differences can be detected with a multiplexed HSP assay panel.
Al Kamaly O, Sayedahmed M, Abdelzaher AM.
Sci Rep
PMID:42010288
Free PMC article
Two simple and selective spectrophotometric methods, ratio difference and derivative ratio, were developed and validated for the simultaneous determination of etoricoxib and tramadol in binary mixtures and pharmaceutical formulations. The methods effectively resolved the sever spectral overlap of both drugs without prior separation. In the ratio difference method, amplitude differences between 294 and 239 nm for etoricoxib and 218 and 272 nm for tramadol showed excellent linearity. In the derivative ratio method, derivative amplitudes measured at 287 nm etoricoxib, and 229 nm tramadol provided high selectivity and sensitivity. The linear ranges were 2-23 µg/mL for etoricoxib and 3-40 µg/mL for tramadol, with correlation coefficients above 0.999. Both methods achieved recoveries between 98.78 and 101.09% and precision values (%RSD) below 2%. Statistical comparison with a reported HPLC method showed no significant difference. The proposed methods are accurate, cost-effective, and supported by AGREE-based greenness assessment, making them suitable for routine quality control of etoricoxib and tramadol formulations.
Tahlan S, Singh S, Dey H, Kaira M, Pandey KC.
Future Med Chem
PMID:42003351
Free PMC article
Diabetes mellitus represents a global health crisis requiring innovative therapeutic strategies beyond traditional treatments. This comprehensive review analyzes heterocyclic frameworks developed between 2020-2024 for antidiabetic drug discovery, highlighting structure-activity relationships (SAR), molecular docking insights, and therapeutic mechanisms. Key scaffold classes emerged as potent antidiabetic agents, with benzimidazoles and triazoles demonstrating dual α-amylase/α-glucosidase inhibition (IC 50 values 1.20-22.46 µg/mL), thiazolidinediones and quinazolines showing PPAR-γ agonism with improved insulin sensitivity and reduced cardiovascular risks, DPP-4 inhibitory scaffolds (pyrrolidines, pyrimidines) achieving IC 50 values as low as 0.021 µM, and SGLT2-targeting heterocycles exhibiting glucose-lowering effects with cardio-renal protection. Major findings revealed that electron-donating groups (methoxy, hydroxyl) consistently enhanced binding affinity across multiple targets, halogen substitutions (fluoro, chloro, bromo) improved metabolic stability and selectivity, hybrid molecules combining multiple pharmacophores achieved superior multi-target effects, and natural product-derived heterocycles (flavonoids, coumarins, alkaloids) showed IC 50 values 10-100× better than acarbose. Emerging frontiers include multi-agonist therapies (GLP-1/GIP, dual SGLT1/SGLT2 inhibitors), glucokinase activators for insulin-independent glucose control, microbiome-targeting agents, and AI-driven rational drug design integrating SAR, docking, and ADMET prediction. This review provides a strategic framework for developing safer, more selective antidiabetic agents through systematic exploitation of heterocyclic chemistry, advancing toward personalized diabetes management.
