Bioanalysis and Metabolomics, 2nd Edition

A special issue of Pharmaceutics (ISSN 1999-4923). This special issue belongs to the section "Pharmacokinetics and Pharmacodynamics".

Deadline for manuscript submissions: closed (20 May 2024) | Viewed by 9899

Special Issue Editors


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Guest Editor
College of Pharmacy and Research Institute of Pharmaceutical Sciences, Kyungpook National University, Daegu 41566, Republic of Korea
Interests: drug metabolism; metabolomics; lipidomics
Special Issues, Collections and Topics in MDPI journals

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Guest Editor
College of Pharmacy, The Catholic University of Korea, Bucheon 14662, Republic of Korea
Interests: bioanalysis; drug metabolism; pharmacokinetics; drug interactions
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Recently, techniques for analyzing endogenous and exogenous substances present in biological samples have been developed due to the development of analytical instruments that combine chromatography and mass spectrometry. As a result, as micro-analysis of drugs is possible, microdosing methods for studying the pharmacokinetics of drugs in humans through the administration of sub-therapeutic doses have been developed and applied in clinical trials. In addition, metabolomics techniques that target endogenous substances in biological samples have been developed, and various studies on biomarkers that can be used to diagnose the disease early and evaluate the efficacy of drugs have been actively conducted. This Special Issue aims to highlight current progress in bioanalysis related to drug metabolism and pharmacokinetics and drug- and disease-related metabolomics.

Prof. Dr. Kwang-Hyeon Liu
Prof. Dr. Hye Suk Lee
Guest Editors

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Keywords

  • bioanalysis
  • method validation
  • pharmacokinetics
  • metabolomics
  • lipidomics
  • biomarkers
  • mass spectrometry

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Related Special Issue

Published Papers (5 papers)

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Research

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21 pages, 2207 KiB  
Article
Pharmacokinetics and Enterohepatic Circulation of 2-(Quinoline-8-carboxamido)benzoic Acid (2-QBA) in Mice
by Ji-Hyeon Jeon, So-Yeon Jeon, Yeon-Ju Baek, Chan-E Park, Min-Koo Choi, Young Taek Han and Im-Sook Song
Pharmaceutics 2024, 16(7), 934; https://doi.org/10.3390/pharmaceutics16070934 - 12 Jul 2024
Viewed by 734
Abstract
The quinoline alkaloid 2-(quinoline-8-carboxamido)benzoic acid (2-QBA), which is isolated from Aspergillus sp. SCSIO06786, a deep sea-derived fungus, has been suggested as a therapeutic candidate for the treatment of Parkinson’s disease. We developed an analytical method for 2-QBA using a liquid chromatography–tandem mass spectrometry [...] Read more.
The quinoline alkaloid 2-(quinoline-8-carboxamido)benzoic acid (2-QBA), which is isolated from Aspergillus sp. SCSIO06786, a deep sea-derived fungus, has been suggested as a therapeutic candidate for the treatment of Parkinson’s disease. We developed an analytical method for 2-QBA using a liquid chromatography–tandem mass spectrometry (LC-MS/MS) in mouse plasma, in which a protein precipitation method for the sample preparation of 2-QBA in mouse plasma was used due to its simplicity and good extraction recovery rates (80.49–97.56%). The linearity of the calibration standard sample, inter- and intraday precision and accuracy, and stability of three quality control samples were suitable based on the assessment criteria and the lower limit of quantification (LLOQ) of the 2-QBA was 1 ng/mL. A pharmacokinetic study of 2-QBA was performed in mice divided into oral (2.0, 5.0, and 15 mg/kg) and intravenous (0.5 and 1.0 mg/kg) administration groups. The absolute oral bioavailability (BA) range of 2-QBA was calculated as 68.3–83.7%. Secondary peaks were observed at approximately 4–8 h after the oral administration of 2-QBA at all doses. The elimination half-life of the orally administered 2-QBA was significantly longer than that of the intravenous 2-QBA. In addition, glucuronide metabolites of 2-QBA were identified. They were transformed into 2-QBA using the β-glucuronidase treatment. Furthermore, the 2-QBA was readily absorbed from the jejunum to lower ileum. Taken together, the secondary peaks could be explained by the enterohepatic circulation of 2-QBA. In conclusion, the reabsorption of orally administered 2-QBA could contribute to the high oral BA of 2-QBA and could be beneficial for the efficacy of 2-QBA. Moreover, the simple and validated analytical method for 2-QBA using LC-MS/MS was applied to the pharmacokinetic study and BA assessments of 2-QBA in mice and would be helpful for subsequent pharmacokinetic studies, as well as for evaluations of the toxicokinetics and pharmacokinetic–pharmacodynamic correlation of 2-QBA to assess its potential as a drug. Full article
(This article belongs to the Special Issue Bioanalysis and Metabolomics, 2nd Edition)
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14 pages, 3236 KiB  
Article
Evaluation of the Drug-Induced Liver Injury Potential of Saxagliptin through Reactive Metabolite Identification in Rats
by Ki-Young Kim, Yeo-Jin Jeong, So-Young Park, Eun-Ji Park, Ji-Hyeon Jeon, Im-Sook Song and Kwang-Hyeon Liu
Pharmaceutics 2024, 16(1), 106; https://doi.org/10.3390/pharmaceutics16010106 - 13 Jan 2024
Viewed by 1757
Abstract
A liver injury was recently reported for saxagliptin, which is a dipeptidyl peptidase-4 (DPP-4) inhibitor. However, the underlying mechanisms of saxagliptin-induced liver injury remain unknown. This study aimed to evaluate whether saxagliptin, a potent and selective DPP-4 inhibitor that is globally used for [...] Read more.
A liver injury was recently reported for saxagliptin, which is a dipeptidyl peptidase-4 (DPP-4) inhibitor. However, the underlying mechanisms of saxagliptin-induced liver injury remain unknown. This study aimed to evaluate whether saxagliptin, a potent and selective DPP-4 inhibitor that is globally used for treating type 2 diabetes mellitus, binds to the nucleophiles in vitro. Four DPP-4 inhibitors, including vildagliptin, were evaluated for comparison. Only saxagliptin and vildagliptin, which both contain a cyanopyrrolidine group, quickly reacted with L-cysteine to enzyme-independently produce thiazolinic acid metabolites. This saxagliptin–cysteine adduct was also found in saxagliptin-administered male Sprague–Dawley rats. In addition, this study newly identified cysteinyl glycine conjugates of saxagliptin and 5-hydroxysaxagliptin. The observed metabolic pathways were hydroxylation and conjugation with cysteine, glutathione, sulfate, and glucuronide. In summary, we determined four new thiazoline-containing thiol metabolites (cysteine and cysteinylglycine conjugates of saxagliptin and 5-hydroxysaxagliptin) in saxagliptin-administered male rats. Our results reveal that saxagliptin can covalently bind to the thiol groups of cysteine residues of endogenous proteins in vivo, indicating the potential for saxagliptin to cause drug-induced liver injury. Full article
(This article belongs to the Special Issue Bioanalysis and Metabolomics, 2nd Edition)
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12 pages, 1876 KiB  
Article
Preclinical Bioavailability Assessment of a Poorly Water-Soluble Drug, HGR4113, Using a Stable Isotope Tracer
by Eun Ji Ha, Jeong In Seo, Shaheed Ur Rehman, Hyung Soon Park, Sang-Ku Yoo and Hye Hyun Yoo
Pharmaceutics 2023, 15(6), 1684; https://doi.org/10.3390/pharmaceutics15061684 - 8 Jun 2023
Cited by 1 | Viewed by 1490
Abstract
Drug solubility limits intravenous dosing for poorly water-soluble medicines, which misrepresents their bioavailability estimation. The current study explored a method using a stable isotope tracer to assess the bioavailability of drugs that are poorly water-soluble. HGR4113 and its deuterated analog, HGR4113-d7, were tested [...] Read more.
Drug solubility limits intravenous dosing for poorly water-soluble medicines, which misrepresents their bioavailability estimation. The current study explored a method using a stable isotope tracer to assess the bioavailability of drugs that are poorly water-soluble. HGR4113 and its deuterated analog, HGR4113-d7, were tested as model drugs. To determine the level of HGR4113 and HGR4113-d7 in rat plasma, a bioanalytical method using LC-MS/MS was developed. The HGR4113-d7 was intravenously administered to rats that were orally pre-administered HGR4113 at different doses; subsequently, the plasma samples were collected. HGR4113 and HGR4113-d7 were simultaneously determined in the plasma samples, and bioavailability was calculated using plasma drug concentration values. The bioavailability of HGR4113 was 53.3% ± 19.5%, 56.9% ± 14.0%, and 67.8% ± 16.7% after oral dosages of 40, 80, and 160 mg/kg, respectively. By eliminating the differences in clearance between intravenous and oral dosages at different levels, acquired data showed that the current method reduced measurement errors in bioavailability when compared to the conventional approach. The present study suggests a prominent method for evaluating the bioavailability of drugs with poor aqueous solubility in preclinical studies. Full article
(This article belongs to the Special Issue Bioanalysis and Metabolomics, 2nd Edition)
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21 pages, 1122 KiB  
Article
An Approach to Evaluate the Effective Cytoplasmic Concentration of Bioactive Agents Interacting with a Selected Intracellular Target Protein
by Yuri V. Khramtsov, Alexey V. Ulasov, Andrey A. Rosenkranz, Tatiana A. Slastnikova, Tatiana N. Lupanova, Georgii P. Georgiev and Alexander S. Sobolev
Pharmaceutics 2023, 15(2), 324; https://doi.org/10.3390/pharmaceutics15020324 - 18 Jan 2023
Cited by 5 | Viewed by 1766
Abstract
To compare the effectiveness of various bioactive agents reversibly acting within a cell on a target intracellular macromolecule, it is necessary to assess effective cytoplasmic concentrations of the delivered bioactive agents. In this work, based on a simple equilibrium model and the cellular [...] Read more.
To compare the effectiveness of various bioactive agents reversibly acting within a cell on a target intracellular macromolecule, it is necessary to assess effective cytoplasmic concentrations of the delivered bioactive agents. In this work, based on a simple equilibrium model and the cellular thermal shift assay (CETSA), an approach is proposed to assess effective concentrations of both a delivered bioactive agent and a target protein. This approach was tested by evaluating the average concentrations of nuclear factor erythroid 2-related factor 2 (Nrf2) and Kelch-like ECH-associated-protein 1 (Keap1) proteins in the cytoplasm for five different cell lines (Hepa1, MEF, RAW264.7, 3LL, and AML12) and comparing the results with known literature data. The proposed approach makes it possible to analyze both binary interactions and ternary competition systems; thus, it can have a wide application for the analysis of protein–protein or molecule–protein interactions in the cell. The concentrations of Nrf2 and Keap1 in the cell can be useful not only in analyzing the conditions for the activation of the Nrf2 system, but also for comparing the effectiveness of various drug delivery systems, where the delivered molecule is able to interact with Keap1. Full article
(This article belongs to the Special Issue Bioanalysis and Metabolomics, 2nd Edition)
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Review

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26 pages, 2272 KiB  
Review
Comprehensive Two-Dimensional Gas Chromatography as a Bioanalytical Platform for Drug Discovery and Analysis
by Atiqah Zaid, Norfarizah Hanim Hassan, Philip J. Marriott and Yong Foo Wong
Pharmaceutics 2023, 15(4), 1121; https://doi.org/10.3390/pharmaceutics15041121 - 31 Mar 2023
Cited by 5 | Viewed by 3348
Abstract
Over the last decades, comprehensive two-dimensional gas chromatography (GC×GC) has emerged as a significant separation tool for high-resolution analysis of disease-associated metabolites and pharmaceutically relevant molecules. This review highlights recent advances of GC×GC with different detection modalities for drug discovery and analysis, which [...] Read more.
Over the last decades, comprehensive two-dimensional gas chromatography (GC×GC) has emerged as a significant separation tool for high-resolution analysis of disease-associated metabolites and pharmaceutically relevant molecules. This review highlights recent advances of GC×GC with different detection modalities for drug discovery and analysis, which ideally improve the screening and identification of disease biomarkers, as well as monitoring of therapeutic responses to treatment in complex biological matrixes. Selected recent GC×GC applications that focus on such biomarkers and metabolite profiling of the effects of drug administration are covered. In particular, the technical overview of recent GC×GC implementation with hyphenation to the key mass spectrometry (MS) technologies that provide the benefit of enhanced separation dimension analysis with MS domain differentiation is discussed. We conclude by highlighting the challenges in GC×GC for drug discovery and development with perspectives on future trends. Full article
(This article belongs to the Special Issue Bioanalysis and Metabolomics, 2nd Edition)
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