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1.
Small ; : e2311990, 2024 May 07.
Article in English | MEDLINE | ID: mdl-38712451

ABSTRACT

This study investigates the origin of low-pressure hysteresis (LPH) in the adsorption and desorption of three different probe molecules: carbon dioxide, nitrogen, and argon, across various adsorption temperatures (from cryogenic to room temperature), and within five different carbon materials: synthetic carbons (pristine and one post-synthetically oxidized) and natural coal. Significant attention is dedicated to elucidating LPH in oxidized samples outgassed at various temperatures (120-350 °C). Experimental results show that insufficient outgassing temperature can lead to unreliable data due to artificial LPH and significantly underestimated textural properties, primarily caused by porosity blockage from substances like moisture. Conversely, in samples where heteroatoms have a stabilizing effect on texture, such as natural coal, careful consideration of outgassing temperature is crucial due to the risk of thermal degradation. Other factors contributing to LPH are adsorption temperature, and especially, kinetic limitations at cryogenic temperatures for cellulose-based carbons. Minor factors responsible for LPH are the physical state of the sample (monolith vs powder) and the flexibility of the porous system, both studied by carbon dioxide sorption. This study constitutes an important piece in the evaluation of LPH, providing practical recommendations and underlining the importance of experimental design, with implications for further research in this complex field.

2.
J Pharm Biomed Anal ; 137: 70-77, 2017 Apr 15.
Article in English | MEDLINE | ID: mdl-28092857

ABSTRACT

Efavirenz is an antiretroviral drug used in the treatment of HIV-positive patients. A simple, fast and sensitive high-performance liquid chromatography (HPLC) method was developed in order to determine efavirenz in three types of samples provided from pharmacokinetic studies. The analysis took 5min and was performed using a C18 analytical column (Discovery HS C18, 150×4.6mm, particle size of 5µm) in isocratic mode with a mobile phase containing acetonitrile and water (65:35, v/v), a flow rate of 1.6mLmin-1, a sample volume of 10µL and UV detection at 245nm. Three different sample matrices (Opti-MEM medium, Krebs perfusion liquid and tissue lysate) and their treatment (dilution, SPE) were considered. The validated method was applied for the analysis of 805 real samples arising from in vitro transcellular transport assays and in vivo organ perfusion experiments in order to evaluate the interaction of efavirenz with ATP-dependent drug efflux transporters. The lack of interaction of efavirenz with ABCB1, ABCG2 and ABCC2 transporters as well as technical aspects of this analysis, including the adhesion of efavirenz to the plastic materials and the stability of the drug during different tissue lysis approaches are discussed.


Subject(s)
Benzoxazines/chemistry , Benzoxazines/metabolism , Placenta/chemistry , ATP Binding Cassette Transporter, Subfamily B, Member 1/metabolism , ATP Binding Cassette Transporter, Subfamily G, Member 2/metabolism , Acetonitriles/chemistry , Alkynes , Animals , Biological Transport/physiology , Cell Line , Chromatography, High Pressure Liquid/methods , Cyclopropanes , Dogs , Drug Stability , Female , Madin Darby Canine Kidney Cells , Multidrug Resistance-Associated Protein 2 , Multidrug Resistance-Associated Proteins/metabolism , Perfusion , Pregnancy , Rats , Rats, Wistar , Reproducibility of Results
3.
Anal Bioanal Chem ; 408(3): 971-81, 2016 Jan.
Article in English | MEDLINE | ID: mdl-26615589

ABSTRACT

A novel flow-programming setup based on the sequential injection principle is herein proposed for on-line monitoring of temporal events in cell permeation studies. The permeation unit consists of a Franz cell with its basolateral compartment mixed under mechanical agitation and thermostated at 37 °C. The apical compartment is replaced by commercially available Transwell inserts with a precultivated cell monolayer. The transport of drug substances across epithelial cells genetically modified with the P-glycoprotein membrane transporter (MDCKII-MDR1) is monitored on-line using rhodamine 123 as a fluorescent marker. The permeation kinetics of the marker is obtained in a fully automated mode by sampling minute volumes of solution from the basolateral compartment in short intervals (10 min) up to 4 h. The effect of a P-glycoprotein transporter inhibitor, verapamil as a model drug, on the efficiency of the marker transport across the cell monolayer is thoroughly investigated. The analytical features of the proposed flow method for cell permeation studies in real time are critically compared against conventional batch-wise procedures and microfluidic devices.


Subject(s)
Automation/methods , Epithelial Cells/metabolism , Flow Injection Analysis/methods , Verapamil/metabolism , ATP Binding Cassette Transporter, Subfamily B, Member 1/metabolism , Biological Transport , Epithelial Cells/chemistry , Flow Injection Analysis/instrumentation , Humans , Kinetics , Rhodamine 123/chemistry , Rhodamine 123/metabolism , Verapamil/chemistry
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