An extension of biorelevant fed-state dissolution tests to clinical pharmacokinetics - A study on gastrointestinal factors influencing rivaroxaban exposure and efficacy in atrial fibrillation patients.

A direct oral anticoagulant rivaroxaban fails to prevent stroke and systemic embolism in one-to-several percent of patients with nonvalvular atrial fibrillation (NVAF), but the reasons are unknown. The study used semi-mechanistic in vitro-in vivo prediction (IVIVP) modeling to explore the reasons for ineffective thrombosis prevention in NVAF patients. Steady-state drug concentrations in plasma were measured at 0 h (C), 3 h (C), and 12 h post-dosing in thirty-four patients treated with 20 mg rivaroxaban daily.

How does the order of sample analysis influence the matrix effect during LC-MS bioanalysis?

Mass spectrometry coupled with liquid chromatography is a valuable tool for drug development and personalised drug therapy. The matrix effect is caused by enhancing or suppressing the analyte signal intensity by the interfering compounds of biological fluids. The matrix effect may influence the reliability of the quantitative results.

Polytyramine Film-Coated Single-Walled Carbon Nanotube Electrochemical Chemosensor with Molecularly Imprinted Polymer Nanoparticles for Duloxetine-Selective Determination in Human Plasma.

We devised, fabricated, and tested differential pulse voltammetry (DPV) and impedance spectroscopy (EIS) chemosensors for duloxetine (DUL) antidepressant determination in human plasma. Polyacrylic nanoparticles were synthesized by precipitation polymerization and were molecularly imprinted with DUL (DUL-nanoMIPs). Then, together with the single-walled carbon nanotube (SWCNT) scaffolds, they were uniformly embedded in polytyramine films, i.

Replicates Number for Drug Stability Testing during Bioanalytical Method Validation-An Experimental and Retrospective Approach.

Background: The stability of a drug or metabolites in biological matrices is an essential part of bioanalytical method validation, but the justification of its sample size (replicates number) is insufficient. The international guidelines differ in recommended sample size to study stability from no recommendation to at least three quality control samples. Testing of three samples may lead to results biased by a single outlier.

LC-MS/MS determination of dutasteride and its major metabolites in human plasma.

Dutasteride is a specific and selective inhibitor of both 5α-reductase isoforms used mainly in benign prostatic hyperplasia and lower urinary tract symptoms. Although the drug is extensively metabolized in humans, data on the concentrations of its main metabolites are lacking. There is also a lack of data on dutasteride stability in frozen plasma samples.

Determination of Antidepressants in Human Plasma by Modified Cloud-Point Extraction Coupled with Mass Spectrometry.

Cloud-point extraction (CPE) is rarely combined with liquid chromatography coupled to mass spectrometry (LC-MS) in drug determination due to the matrix effect (ME). However, we have recently shown that ME is not a limiting factor in CPE. Low extraction efficiency may be improved by salt addition, but none of the salts used in CPE are suitable for LC-MS.

Quantitative evaluation of the matrix effect in bioanalytical methods based on LC-MS: A comparison of two approaches.

Liquid chromatography coupled to mass spectrometry (LC-MS) is a powerful tool for studying pharmacokinetics and toxicokinetics. Reliable bioanalysis requires the characterization of the matrix effect, i.e.