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Sitagliptin is an orally bioavailable selective DPP4 inhibitor that reduces blood glucose levels without significant increases in hypoglycemia. The aim of this study was to design and validate an innovative, rapid, and highly sensitive LC–MS/MS assay for the precise measurement of sitagliptin concentrations in human plasma. This analytical method, utilizing sitagliptin-d4 as the internal standard, is performed using only 100 μL of plasma and a liquid–liquid extraction procedure based on methyl tert-butyl ether (MTBE). Chromatographic separation is expertly achieved with a Kinetex® C18 column under isocratic elution, employing a perfect 1:1 blend of 5 mM ammonium acetate (with 0.04% formic acid) and acetonitrile, and maintaining an efficient flow rate of 0.2 mL/min. Detection occurs in positive ionization mode through multiple reaction monitoring, precisely targeting transitions of m/z 408.2 → 193.0 for sitagliptin and 412.2 → 239.1 for the IS. The total runtime of this assay is under 2 min. Comprehensive validation in line with MFDS and FDA criteria demonstrates outstanding linearity (5–1000 ng/mL, r2 > 0.998), alongside impressive levels of accuracy, precision, recovery and sample stability. Due to its minimal sample requirement and high-throughput capability, the validated approach is highly appropriate for pharmacokinetic and bioequivalence assessments involving sitagliptin.

Glimepiride remains a cost-effective antidiabetic treatment despite its potential risks. However, its interaction with traditional medicines like Ojeok-san (OJS), a commonly used herbal medication, warrants investigation. This open-label, fixed-sequence, two-period, two-treatment crossover study involved 17 healthy male volunteers. Subjects received glimepiride 4 mg once daily for 2 days in period 1, followed by OJS 4.35 g three times daily for 8 days, with concurrent glimepiride administration on the final two days in period 2. Co-administration of OJS with glimepiride resulted in pharmacokinetic changes. The mean area under the plasma concentration-time curve (AUC) from dosing to 24 h post-dosing (AUC 0–24 h ) of glimepiride decreased from 1283.53 ng∙h/mL to 1125.27 ng∙h/mL, and the mean maximum concentration (C max ) reduced from 250.76 ng/mL to 209.38 ng/mL when compared to glimepiride alone. OJS co-administration also prolonged the median time to reach maximum concentration (T max ) and half-life (t 1/2 ). The study demonstrated pharmacokinetic interactions between glimepiride and OJS, showing reduced systemic exposure and altered elimination patterns of glimepiride during co-administration.

A highly accurate, precise, and simple liquid chromatography-tandem mass spectrometry (LC–MS/MS) method for ketotifen (KTF) estimation from Beagle dog plasma was developed and validated, with ketotifen-d3 (KTF-d3) as the internal standard (IS). KTF and IS were detected on an API 4000 mass spectrometer in multiple reaction monitoring (MRM) mode in electrospray ionization (ESI) positive ionization mode. The transitions were monitored at m/z 310.2 → 96.0 for KTF and m/z 313.2 → 99.1 for IS. KTF and IS were extracted from plasma using liquid-liquid extraction with methyl tertiary-butyl ether and then analyzed for 3 min with extracted samples (7 µL) into the LC–MS/MS system. Analytes were separated on a Luna® Hilic column (50 × 2.0 mm i.d., 3 μm) using the Nexera X2 HPLC. The mobile phase A consisted of 10 mmol/L ammonium formate (pH 3.0), while mobile phase B consisted of 0.05% formic acid in acetonitrile. The ratio of mobile phase was 5:95 (v/v) at a flow rate of 0.2 mL/min. The method has been thoroughly validated in accordance with the bioanalytical method validation guidelines established by the Ministry of Food and Drug Safety in Korea and the U.S. Food and Drug Administration, addressing selectivity, lower limit of quantification, linearity, carryover, precision, accuracy, recovery, matrix effect, and stability. The developed LC–MS/MS method was effectively utilized for the bioequivalence assessment of ketotifen in Beagle dog plasma following the oral administration of ketotifen syrup.

Background/Objectives: Selinexor is a selective nuclear-export inhibitor approved for hematologic malignancies, characterized by extensive plasma protein binding (>95%). However, a validated analytical method to accurately measure the clinically relevant unbound fraction of selinexor in human plasma has not yet been established. This study aimed to develop a fully validated bioanalytical assay for simultaneous quantification of total and unbound selinexor concentrations in human plasma. Methods: We established and fully validated an analytical method based on liquid chromatography–tandem mass spectrometry (LC-MS/MS) capable of quantifying total and unbound selinexor concentrations in human plasma. Unbound selinexor was separated using ultrafiltration, and selinexor was efficiently extracted from 50 μL of plasma by liquid–liquid extraction. Chromatographic separation was achieved on a C18 column using an isocratic mobile phase (0.1% formic acid:methanol, 12:88 v/v) with a relatively short runtime of 2.5 min. Results: Calibration curves showed excellent linearity over a range of 5–2000 ng/mL for total selinexor (r2 ≥ 0.998) and 0.05–20 ng/mL for unbound selinexor (r2 ≥ 0.995). The precision (%CV ≤ 10.35%) and accuracy (92.5–104.3%) for both analytes met the regulatory criteria. This method successfully quantified selinexor in plasma samples from renally impaired patients with multiple myeloma, demonstrating potential inter-individual differences in unbound drug concentrations. Conclusions: This validated bioanalytical assay enables precise clinical pharmacokinetic assessments in a short runtime using a small plasma volume and, thus, assists in individualized dosing of selinexor, particularly for renally impaired patients with altered protein binding.

Background/Objectives: This study aimed to develop a fully validated HPLC-MS/MS method for quantifying total and unbound lenalidomide concentrations in human plasma. Methods: Unbound concentrations were measured using plasma ultrafiltrate prepared with Amicon® Centrifugal Filters. Lenalidomide and lenalidomide-d5 (internal standard) were extracted from 50 μL of human plasma using liquid–liquid extraction. Chromatography was conducted with a Halo® C18 column using 0.1% formic acid and methanol (20:80, v/v) as the mobile phase. The mass spectrometer was operated in a positive ion mode with an electrospray ionization interface and multiple reaction monitoring modes. Results: Calibration curves were linear over the range of 5 to 1000 ng/mL (r2 > 0.996) for both the total and unbound lenalidomide. For total lenalidomide concentrations, between-run precision (coefficients of variation) and accuracy were 1.70–7.65% and 94.45–101.10%, respectively. For unbound concentrations, inter-day precision and accuracy were 1.98–10.55% and 93.95–98.48%, respectively. Conclusions: We developed a highly reproducible, sensitive, and efficient bioanalytical method using a smaller volume of plasma sample (50 μL) with a relatively short run time (2.5 min). The proposed analytical method was successfully applied to measure total and unbound lenalidomide concentrations at various time points in multiple myeloma patients with renal impairment.

This study developed a simple, rapid, reproducible, and analytical method using liquid chromatography and electrospray ionization (ESI) with tandem mass spectrometry (LC-MS/MS) to simultaneously quantify pentoxifylline (PTX), its pharmacological active metabolites, lisofylline (PTX-M1) and 1-(3-carboxypropyl)-3,7-dimethylxanthine (PTX-M5), and donepezil (DNP) in rat plasma, using PTX-d6 and DNP-d7 as the internal standards. The LC-MS/MS procedure was performed at the ESI interface, operating in positive ionization and multiple reaction monitoring (MRM) modes; the monitoring of transitions comprised m/z 279.3 > 181.1 for PTX, m/z 281.1 > 263.1 > 160.90 for PTX-M1, m/z 267.1 > 249.0 > 220.9 for PTX-M5, m/z 380.3 > 90.9 for DNP, m/z 285.3 > 187.1 for PTX-d6 (IS1), and m/z 387.3 > 98.3 for DNP-d7 (IS2). After plasma protein precipitation (PP) with methanol, chromatographic separation was performed with an Imtakt Cadenza® CD-C18 (100 × 3 mm, 3 µm) column, using an isocratic mobile phase consisting of 0.1% formic acid in water and methanol (20:80, v/v) at a flow rate of 0.2 mL/min. The retention times of DNP, PTX-M5, PTX, and PTX-M1 were 2.24, 2.50, 2.68, and 2.72 min, respectively, with a total run time of 5 min. This method was validated over a linear concentration range of 5–8000, 10–5000, 20–15,000, and 2–500 ng mL−1 for PTX, PTX-M1, PTX-M5, and DNP, respectively, with a high correlation coefficient (r2 ≥ 0.99). The established method was fully validated in terms of selectivity, the lower limit of quantitation, precision, accuracy, recovery, matrix effect, stability, and dilution integrity according to the regulatory guidelines from the U.S. Food and Drug Administration and the Korea Ministry of Food and Drug Safety. The validated method was successfully applied to a pharmacokinetic study on the concurrent administration of DNP and PTX in rats.

This review into recent advancements in silicon-based technology, with a particular emphasis on the biomedical applications of silicon sensors. Owing to their diminutive size, high sensitivity, and intrinsic compatibility with electronic systems, silicon-based sensors have found widespread utilization across healthcare, industrial, and environmental monitoring domains. In the realm of biomedical sensing, silicon has demonstrated significant potential to enhance human health outcomes while simultaneously driving progress in microfabrication techniques for multifunctional device development. The review systematically examines the versatile roles of silicon in the fabrication of electrodes, sensing channels, and substrates. Silicon electrodes are widely used in electrochemical biosensors for glucose monitoring and neural activity recording, while sensing channels in field-effect transistor biosensors enable the detection of cancer biomarkers and small molecules. Porous silicon substrates are applied in optical biosensors for label-free protein and pathogen detection. Key challenges in this field, including the interaction of silicon with biomolecules, the economic barriers to miniaturization, and issues related to signal stability, are critically analyzed. Proposed strategies to address these challenges and improve sensor functionality and reliability are also discussed. Furthermore, the article explores emerging developments in silicon-based biosensors, particularly their integration into wearable technologies. The pivotal role of artificial intelligence (AI) in enhancing the performance, functionality, and real-time capabilities of these sensors is also highlighted. This review provides a comprehensive overview of the current state, challenges, and future directions in the field of silicon-based biomedical sensing technologies.

The impact of microplastics (MPs) on the metabolic functions of the liver is currently unclear and not completely understood. To investigate the effects of the administration of MPs on the hepatic metabolism of normal and obese mice, alterations in the lipid, glucose (Glu), and amino acid regulation pathways were analyzed in the liver and adipose tissues of C57BL/6Korl (wild type, WT) or C57BL/6-Lepem1hwl/Korl mice (leptin knockout, Lep KO) orally administered polystyrene (PS) MPs for 9 weeks. Significant alterations in the lipid accumulation, adipogenesis, lipogenesis, and lipolysis pathways were detected in the liver tissue of MP-treated WT and Lep KO mice compared to the vehicle-treated group. These alterations in their liver tissues were accompanied by an upregulation of the serum lipid profile, as well as alterations in the adipogenesis, lipogenesis, and lipolysis pathways in the adipose tissues of MP-treated WT and Lep KO mice. Specifically, the level of leptin was increased in the adipose tissues of MP-treated WT mice without any change in their food intake. Also, MP-induced disruptions in the glycogenolysis, Glu transporter type 4 (GLUT4)-5′ AMP-activated protein kinase (AMPK) signaling pathway, levels of lipid intermediates, and the insulin resistance of the liver tissues of WT and Lep KO mice were observed. Furthermore, the levels of seven endogenous metabolites were remarkably changed in the serum of WT and Lep KO mice after MP administrations. Finally, the impact of the MP administration observed in both types of mice was further verified in differentiated 3T3-L1 adipocytes and HepG2 cells. Thus, these results suggest that the oral administration of MPs for 9 weeks may be associated with the disruption of lipid, Glu, and amino acid metabolism in the liver tissue of obese WT and Lep KO mice.

Monitoring and assessing the progression of symptoms in neurodegenerative diseases, including Alzheimer’s and Parkinson’s disease, are critical for improving patient outcomes. Traditional biomarkers, such as cerebrospinal fluid analysis and brain imaging, are widely used to investigate the underlying mechanisms of disease and enable early diagnosis. In contrast, digital biomarkers derived from phenotypic changes—such as EEG, eye movement, gait, and speech analysis—offer a noninvasive and accessible alternative. Leveraging portable and widely available devices, such as smartphones and wearable sensors, digital biomarkers are emerging as a promising tool for ND diagnosis and monitoring. This review highlights the comprehensive developments in digital biomarkers, emphasizing their unique advantages and integration potential alongside traditional biomarkers.

Canine influenza virus (CIV) H3N2 continues to circulate among companion animals, posing a zoonotic risk due to its potential for cross-species transmission. However, currently available inactivated vaccines offer limited mucosal immunity and suboptimal protection. Here, we developed a novel intranasal live attenuated CIV H3N2 vaccine carrying a truncated nonstructural protein 1 (NS1) gene and evaluated its safety, immunogenicity, and protective efficacy in beagle dogs. The NS1-truncated LAIV was well-tolerated and induced robust mucosal and systemic immune responses, including high titers of virus-specific secretory IgA. Following challenge with virulent CIV H3N2 at 120 days post-vaccination, LAIV-immunized dogs exhibited complete clinical protection and minimal viral shedding, whereas dogs receiving the inactivated vaccine showed moderate disease signs. These findings demonstrate that the NS1-truncated LAIV confers superior protection compared to conventional vaccines and represents a promising next-generation platform for canine influenza control within a One Health framework.