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Pharmaceuticals
Special Issues
Innovative Tools for Drug Analysis and Therapeutic Drug Monitoring (TDM)
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Innovative Tools for Drug Analysis and Therapeutic Drug Monitoring (TDM)

A special issue of Pharmaceuticals (ISSN 1424-8247). This special issue belongs to the section "Pharmacology".

Deadline for manuscript submissions: 31 May 2024 | Viewed by 1775

Special Issue Editors

Dr. Juraj Piestansky

E-Mail Website
Guest Editor
Department of Galenic Pharmacy, Faculty of Pharmacy, Comenius University in Bratislava, Odbojarov 10, 832 32 Bratislava, Slovakia
Interests: capillary electrophoresis; liquid chromatography; mass spectrometry; drug analysis; metabolomics; proteomics; therapeutic peptides; bioanalysis
Special Issues, Collections and Topics in MDPI journals
Dr. Andrej Kovac

E-Mail Website
Guest Editor
Institute of Neuroimmunology, Slovak Academy of Sciences, Dubravska Cesta 9, 84510 Bratislava, Slovakia
Interests: Alzheimer's disease; neurodegenerative diseases; neurobiology; cell culture; immunohistochemistry; neurodegeneration; neuroscience; neurological diseases; neurobiology and brain physiology; cellular neuroscience

Special Issue Information

Dear Colleagues,

Therapeutic drug monitoring (TDM) is a measurement of drug concentration in various body fluids or tissues. This field has been developing since the 1980s and is mainly related to the development of specific laboratory methods that allow the determination of the concentration of a drug in biological fluids, most often in serum or urine. Accurate analyses and the proper interpretation of drug concentration can significantly improve the treatment management of individual patients. Excluding “traditional drugs”, among which we include drugs with a narrow therapeutic width, TDM is used for drugs with a well-defined relationship between concentration and effect (either therapeutic or toxic) and drugs with large inter- or intra-individual differences in distribution or in clearance. TDM is also used in clinical practice for other drugs, e.g., β-lactam or peptide antibiotics.

To determine the levels of drugs in biological fluids and/or in dosage forms, accurate analytical methods (e.g., HPLC, CE, MS) are needed. These methods represent an extremely valuable tool in the clinical, quality control, and regulatory environment. They are characterized by robustness, relative simplicity, universality, and the high throughput of samples, which are extremely desirable attributes for the quick decision making needed in the setting/adjustment of pharmacotherapy based on TDM.

Dr. Juraj Piestansky
Dr. Andrej Kovac
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Pharmaceuticals is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • therapeutic drug monitoring
  • analysis of drugs
  • separation analytical methods
  • mass spectrometry
  • bioanalysis
  • quality control
  • dosage forms
  • green analytical chemistry

Published Papers (3 papers)

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Research

22 pages, 2071 KiB  
Article
Development and Validation of a Capillary Zone Electrophoresis–Tandem Mass Spectrometry Method for Simultaneous Quantification of Eight β-Lactam Antibiotics and Two β-Lactamase Inhibitors in Plasma Samples
by Ivana Cizmarova, Peter Mikus, Martin Svidrnoch and Juraj Piestansky
Pharmaceuticals 2024, 17(4), 526; https://doi.org/10.3390/ph17040526 - 19 Apr 2024
Viewed by 349
Abstract
Monitoring plasma concentrations of β-lactam antibiotics is crucial, particularly in critically ill patients, where variations in concentrations can lead to treatment failure or adverse events. Standardized antimicrobial regimens may not be effective for all patients, especially in special groups with altered physiological parameters. [...] Read more.
Monitoring plasma concentrations of β-lactam antibiotics is crucial, particularly in critically ill patients, where variations in concentrations can lead to treatment failure or adverse events. Standardized antimicrobial regimens may not be effective for all patients, especially in special groups with altered physiological parameters. Pharmacokinetic/pharmacodynamic (PK/PD) studies highlight the time-dependent antibacterial activity of these antibiotics, emphasizing the need for personalized dosing. Therapeutic drug monitoring (TDM) is essential, requiring rapid and accurate analytical methods for precise determination of drugs in biological material (typically plasma or serum). This study presents a novel capillary zone electrophoresis–tandem mass spectrometry (CZE-MS/MS) method designed for the simultaneous quantification of five penicillin antibiotics, two cephalosporins, one carbapenem, and two β-lactamase inhibitors in a single run. The method involves a simple sample pretreatment—precipitation with organic solvent—and has a run time of 20 min. Optimization of CZE separation conditions revealed that 20 mM ammonium hydrogen carbonate (NH4HCO3) serves as the optimal background electrolyte (BGE). Positive electrospray ionization (ESI) mode, with isopropyl alcohol (IP)/10 mM ammonium formate water solution (50/50, v/v) as the sheath liquid, was identified as the optimal condition for MS detection. Method validation according to the Food and Drug Administration (FDA) guideline for development of bioanalytical methods demonstrated satisfactory selectivity, linearity, recovery, robustness, and stability. The method’s practicality was evaluated using the Blue Applicability Grade Index (BAGI), yielding a score of 77.5. Moreover, the greenness of the proposed method was evaluated by two commonly used metric tools—Analytical GREEnness (AGREE) and Green Analytical Procedure Index (GAPI). The developed CZE-MS/MS method offers a practical and reliable approach for quantifying a broad spectrum of β-lactam antibiotics in plasma. Its ability to simultaneously quantify multiple analytes in a single run, coupled with a straightforward sample pretreatment, positions it as a valuable and prospective tool for TDM in critically ill patients. Full article
(This article belongs to the Special Issue Innovative Tools for Drug Analysis and Therapeutic Drug Monitoring (TDM))
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15 pages, 8122 KiB  
Article
A Green HPLC Approach to Florfenicol Analysis in Pig Urine
by Ksenija Šandor, Eleonora Perak Junaković, Svjetlana Terzić, Irena Žarković, Anja Vujnović, Dominika Fajdić, Mirta Pehnec, Sonja Sinković, Irena Ćaleta and Miroslav Andrišić
Pharmaceuticals 2024, 17(4), 495; https://doi.org/10.3390/ph17040495 - 12 Apr 2024
Viewed by 415
Abstract
Florfenicol (FF) is a broad-spectrum antibiotic used to treat gastrointestinal and respiratory infections in domestic animals. Considering FF’s rapid elimination via urine after drug treatment, its use increases concerns about environmental contamination. The objective of the study was to establish a sustainable chromatographic [...] Read more.
Florfenicol (FF) is a broad-spectrum antibiotic used to treat gastrointestinal and respiratory infections in domestic animals. Considering FF’s rapid elimination via urine after drug treatment, its use increases concerns about environmental contamination. The objective of the study was to establish a sustainable chromatographic method for simple analysis of FF in pig urine to investigate the urinary excretion of FF after a single intramuscular administration of 20 mg FF/kg body weight. The urine sample was prepared using a centrifuge and regenerated cellulose filter, and the diluted sample was analyzed. The method was validated in terms of linearity, the limit of detection (0.005 µg/mL) and quantitation (0.016 µg/mL), repeatability and matrix effect (%RSD ranged up to 2.5), accuracy (varied between 98% and 102%), and stability. The concentration-time profile of pig urine samples collected within 48 h post-drug administration showed that 63% of FF’s dose was excreted. The developed method and previously published methods used to qualify FF in the urine of animal origin were evaluated by the National Environmental Method Index (NEMI), Green Analytical Procedure Index (GAPI) and Analytical GREENness Metric Approach (AGREE). The greenness profiles of published methods revealed problems with high solvents and energy consumption, while the established method was shown to be more environmentally friendly. Full article
(This article belongs to the Special Issue Innovative Tools for Drug Analysis and Therapeutic Drug Monitoring (TDM))
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12 pages, 1702 KiB  
Article
Application of Liquid Chromatography Coupled to Mass Spectrometry for Direct Estimation of the Total Levels of Adenosine and Its Catabolites in Human Blood
by Jakub Šofranko, Peter Mitro, Zora Lazúrová, Martin Jozef Péč, Tomáš Bolek, Renata Péčová, Matúš Dohál, Matej Samoš and Radovan Murín
Pharmaceuticals 2024, 17(3), 345; https://doi.org/10.3390/ph17030345 - 07 Mar 2024
Viewed by 716
Abstract
Adenosine is a multifunctional nucleoside with several roles across various levels in organisms. Beyond its intracellular involvement in cellular metabolism, extracellular adenosine potently influences both physiological and pathological processes. In relation to its blood level, adenosine impacts the cardiovascular system, such as heart [...] Read more.
Adenosine is a multifunctional nucleoside with several roles across various levels in organisms. Beyond its intracellular involvement in cellular metabolism, extracellular adenosine potently influences both physiological and pathological processes. In relation to its blood level, adenosine impacts the cardiovascular system, such as heart beat rate and vasodilation. To exploit the adenosine levels in the blood, we employed the liquid chromatography method coupled with mass spectrometry (LC–MS). Immediately after collection, a blood sample mixed with acetonitrile solution that is either enriched with 13C-labeled adenosine or a newly generated mixture is transferred into the tubes containing the defined amount of 13C-labeled adenosine. The 13C-enriched isotopic adenosine is used as an internal standard, allowing for more accurate quantification of adenosine. This novel protocol for LC–MS-based estimation of adenosine delivers a rapid, highly sensitive, and reproducible means for quantitative estimation of total adenosine in blood. The method also allows for quantification of a few catabolites of adenosine, i.e., inosine, hypoxanthine, and xanthine. Our current setup did not allow for the detection or quantifying of uric acid, which is the final product of adenosine catabolism. This advancement provides an analytical tool that has the potential to enhance our understanding of adenosine’s systemic impact and pave the way for further investigations into its intricate regulatory mechanisms. Full article
(This article belongs to the Special Issue Innovative Tools for Drug Analysis and Therapeutic Drug Monitoring (TDM))
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