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  • 1
    Online Resource
    Online Resource
    Metabolomic characterisation of progression and spontaneous regression of melanoma in the melanoma-bearing Libechov minipig model
    Ovid Technologies (Wolters Kluwer Health) ; 2021
    In:  Melanoma Research Vol. 31, No. 2 ( 2021-04), p. 140-151
    Details
    In: Melanoma Research, Ovid Technologies (Wolters Kluwer Health), Vol. 31, No. 2 ( 2021-04), p. 140-151
    Abstract: Melanoma-bearing Libechov minipig (MeLiM) represents a large animal model for melanoma research. This model shows a high incidence of complete spontaneous regression of melanoma – a phenomenon uncommon in humans. Here, we present the first metabolomic characterisation of the MeLiM model comparing animals with progressing and spontaneously regressing melanomas. Plasma samples of 19 minipigs with progression and 27 minipigs with evidence of regression were analysed by a targeted metabolomic assay based on mass spectrometry detection. Differences in plasma metabolomics patterns were investigated by univariate and multivariate statistical analyses. Overall, 185 metabolites were quantified in each plasma sample. Significantly altered metabolomic profile was found, and 42 features were differentially regulated in plasma. Besides, the machine learning approach was used to create a predictive model utilising Arg/Orn and Arg/ADMA ratios to discriminate minipigs with progressive disease development from minipigs with regression evidence. Our results suggest that progression of melanoma in the MeLiM model is associated with alteration of arginine, glycerophospholipid and acylcarnitines metabolism. Moreover, this study provides targeted metabolomics characterisation of an animal model of melanoma with progression and spontaneous regression of tumours.
    Type of Medium: Online Resource
    ISSN: 0960-8931
    URL: Article
    DOI: 10.1097/CMR.0000000000000722
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2021
    detail.hit.zdb_id: 1095779-0
    detail.hit.zdb_id: 2030780-9
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  • 2
    Online Resource
    Online Resource
    A high‐throughput LC–MS/MS method for simultaneous determination of isoniazid, ethambutol and pyrazinamide in human plasma
    Wiley ; 2023
    In:  Rapid Communications in Mass Spectrometry Vol. 37, No. 2 ( 2023-01-30)
    Details
    In: Rapid Communications in Mass Spectrometry, Wiley, Vol. 37, No. 2 ( 2023-01-30)
    Abstract: Tuberculosis (TB) remains a challenging global infectious disease, mainly affecting the lungs. First‐line anti‐TB drugs play a crucial role in slowing down the rapid spread of TB. In addition, the patient might benefit from therapeutic drug monitoring since it has become an accepted clinical tool for optimizing TB treatment. Methods A simple and sensitive liquid chromatography/tandem mass spectrometry method was developed to monitor the plasma level of isoniazid, ethambutol and pyrazinamide in plasma samples. A one‐step extraction procedure using an Ostro™ plate was applied, and extracts were analyzed by gradient elution followed by detection on a mass spectrometer by multiple reaction monitoring mode. Results The analytes were separated within 4.2 min and over the concentration range of 0.2–10 μg/ml for isoniazid and ethambutol and 1–65 μg/ml for pyrazinamide. The method was successfully validated according to the European Medicine Agency guideline for the selectivity, linearity and lower limit of detection, precision and accuracy, matrix effect, extraction recovery, carryover, dilution integrity and stability, and applied for quantification of analytes in clinical samples from TB patients. Conclusions The presented method allows sensitive and reproducible determination of selected anti‐TB drugs with advantages such as low sample volume requirement, short run time of analysis, one‐step sample preparation procedure with capabilities for phospholipids removal, and a low quantification limit as well as a high degree of selectivity.
    Type of Medium: Online Resource
    ISSN: 0951-4198 , 1097-0231
    URL: Issue
    URL: Article
    DOI: 10.1002/rcm.v37.2
    DOI: 10.1002/rcm.9425
    Language: English
    Publisher: Wiley
    Publication Date: 2023
    detail.hit.zdb_id: 2002158-6
    detail.hit.zdb_id: 58731-X
    SSG: 11
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  • 3
    Online Resource
    Online Resource
    Volumetric Absorptive Microsampling Technique in the LC-MS Determination of Direct Oral Anticoagulants
    Walter de Gruyter GmbH ; 2023
    In:  Acta Medica Martiniana Vol. 23, No. 1 ( 2023-04-01), p. 23-31
    Details
    In: Acta Medica Martiniana, Walter de Gruyter GmbH, Vol. 23, No. 1 ( 2023-04-01), p. 23-31
    Abstract: Direct oral anticoagulants represent a significant group of drugs used in the prevention or treatment of venous thromboembolic events and stroke in patients with atrial fibrillation. Although routine therapy monitoring is not required, there is an increasing evidence that plasma levels may vary between individuals, suggesting the benefit of plasma levels measurement in some situations. Therapeutic drug monitoring is becoming more popular and accessible to the broader population. Introducing microsampling techniques for the quantitative collection of blood samples has arisen nowadays. The volumetric absorptive microsampling approach using a commercially available device such as a Mitra stick overcomes the hematocrit effect present in the dry blood spot technique. This review discusses the possible application of the volumetric absorptive microsampling approach in monitoring direct oral anticoagulant therapy efficacy.
    Type of Medium: Online Resource
    ISSN: 1338-4139
    URL: Article
    DOI: 10.2478/acm-2023-0004
    Language: English
    Publisher: Walter de Gruyter GmbH
    Publication Date: 2023
    detail.hit.zdb_id: 2558614-2
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  • 4
    Online Resource
    Online Resource
    Biochemical Properties of Atranorin-Induced Behavioral and Systematic Changes of Laboratory Rats
    MDPI AG ; 2022
    In:  Life Vol. 12, No. 7 ( 2022-07-20), p. 1090-
    Details
    In: Life, MDPI AG, Vol. 12, No. 7 ( 2022-07-20), p. 1090-
    Abstract: Atranorin (ATR) is a secondary metabolite of lichens. While previous studies investigated the effects of this substance predominantly in an in vitro environment, in our study we investigated the basic physicochemical properties, the binding affinity to human serum albumin (HSA), basic pharmacokinetics, and, mainly, on the systematic effects of ATR in vivo. Sporadic studies describe its effects during, predominantly, cancer. This project is original in terms of testing the efficacy of ATR on a healthy organism, where we can possibly attribute negative effects directly to ATR and not to the disease. For the experiment, 24 Sprague Dawley rats (Velaz, Únetice, Czech Republic) were used. The animals were divided into four groups. The first group (n = 6) included healthy males as control intact rats (♂INT) and the second group (n = 6) included healthy females as control intact rats (♀INT). Groups three and four (♂ATR/n = 6 and ♀ATR/n = 6) consisted of animals with daily administered ATR (10mg/kg body weight) in an ethanol–water solution per os for a one-month period. Our results demonstrate that ATR binds to HSA near the binding site TRP214 and acts on a systemic level. ATR caused mild anemia during the treatment. However, based on the levels of hepatic enzymes in the blood (ALT, ALP, or bilirubin levels), thiobarbituric acid reactive substances (TBARS), or liver histology, no impact on liver was recorded. Significantly increased creatinine and lactate dehydrogenase levels together with increased defecation activity during behavioral testing may indicate the anabolic effect of ATR in skeletal muscles. Interestingly, ATR changed some forms of behavior. ATR at a dose of 10 mg/kg body weight is non-toxic and, therefore, could be used in further research.
    Type of Medium: Online Resource
    ISSN: 2075-1729
    URL: Article
    DOI: 10.3390/life12071090
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2662250-6
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  • 5
    Online Resource
    Online Resource
    Development of Sensitive and High-Throughput Liquid Chromatography–Tandem Mass Spectrometry Method for Quantification of Haloperidol in Human Plasma with Phospholipid Removal Pretreatment
    Oxford University Press (OUP) ; 2020
    In:  Journal of Analytical Toxicology ( 2020-09-04)
    Details
    In: Journal of Analytical Toxicology, Oxford University Press (OUP), ( 2020-09-04)
    Abstract: Haloperidol, butyrophenone derivative, is a typical antipsychotic drug used in the treatment of schizophrenia, manic phase of bipolar disorder, and acute psychomotor agitations. According to the recent guidelines for therapeutic drug monitoring, it is strongly recommended to measure plasma level during the therapy with haloperidol. The objective of this study was to develop and validate a simple liquid chromatography–tandem mass spectrometry-based method to quantitate haloperidol in human plasma. After one-step extraction procedure using OSTROTM plate, gradient elution on Acquity UPLC BEH C18 (50 × 2.1 mm, 1.7 μm) column over 3.2 min was performed. The detection was conducted on a triple quadrupole tandem mass spectrometer by multiple reaction monitoring mode in positive ionization mode with transitions at m/z 376.29 → 165.14 and m/z 380.28 → 169.17 for haloperidol and haloperidol-d4 (used as an internal standard), respectively. The method was fully validated to cover wide concentration range of 0.05–80 ng/mL in human plasma and meets the criteria for the selectivity, linearity and lower limit of detection, precision and accuracy, matrix effect, extraction recovery, carryover, dilution integrity and stability. The extraction recovery was nearly 100%, and no significant matrix effects were observed. Therefore, the method is applicable to routine therapeutic drug monitoring in patients’ plasma.
    Type of Medium: Online Resource
    ISSN: 0146-4760 , 1945-2403
    URL: Article
    DOI: 10.1093/jat/bkaa124
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2020
    detail.hit.zdb_id: 2010848-5
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  • 6
    Online Resource
    Online Resource
    Simultaneous determination of caffeine and its metabolites in rat plasma by UHPLC‐MS/MS
    Wiley ; 2021
    In:  Journal of Separation Science Vol. 44, No. 23 ( 2021-12), p. 4274-4283
    Details
    In: Journal of Separation Science, Wiley, Vol. 44, No. 23 ( 2021-12), p. 4274-4283
    Abstract: Caffeine is a widely consumed psychostimulant with several mechanisms of action and various positive and negative effects on organisms. Caffeine undergoes extensive hepatic metabolism to form main metabolites such as theobromine, theophylline, paraxanthine, and 1,3,7‐trimethyluric acid. However, interspecies diversities have been observed in caffeine metabolism. In the present study, we developed a sensitive and straightforward ultra‐high‐performance liquid chromatography‐tandem mass spectrometry method to quantify caffeine and its primary metabolites, namely theobromine, theophylline, paraxanthine, and 1,3,7‐trimethyluric acid in rat plasma. After extraction of analytes using micro solid‐phase extraction plate, analytes were separated by elution gradient on the Acquity UPLC HSS T3 (50 × 2.1 mm, 1.8 μm) column over 4 min. The detection was done on a triple quadrupole tandem mass spectrometer by multiple reaction monitoring modes using a positive electrospray ionization interface. The method was successfully validated according to the European Medicine Agency guideline over a concentration range of 5–1500 ng/ml for caffeine, 5–1200 ng/mL for theobromine, and 2.5–1200 ng/mL for theophylline, paraxanthine, and 1,3,7‐trimethyluric acid. The developed method was applied to analyze samples from animal experiments focusing on the metabolism and effects of caffeine and caffeine‐containing beverages.
    Type of Medium: Online Resource
    ISSN: 1615-9306 , 1615-9314
    URL: Issue
    URL: Article
    DOI: 10.1002/jssc.v44.23
    DOI: 10.1002/jssc.202100604
    RVK:
    VA 5450
    Language: English
    Publisher: Wiley
    Publication Date: 2021
    detail.hit.zdb_id: 2047990-6
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  • 7
    Online Resource
    Online Resource
    A high‐throughput liquid chromatography‐tandem mass spectrometry method for simultaneous determination of direct oral anticoagulants in human plasma
    Wiley ; 2023
    In:  Journal of Separation Science Vol. 46, No. 13 ( 2023-07)
    Details
    In: Journal of Separation Science, Wiley, Vol. 46, No. 13 ( 2023-07)
    Abstract: Direct oral anticoagulants are widely used in many indications to prevent thromboembolic events. Routine therapeutic monitoring is not required; however, there is increasing evidence suggesting the benefit of plasma level measurement in some situations. In addition, laboratory monitoring might help improve patient and drug non‐compliance and thus individualize therapy. In the present study, we developed a sensitive and high throughput ultra‐high‐performance liquid chromatography‐tandem mass spectrometry method for simultaneous quantification of apixaban, dabigatran, edoxaban, and rivaroxaban in human plasma. A one‐step extraction procedure in 96‐well formate for phospholipid and protein removal was used for sample pre‐treatment, and analytes were separated using gradient elution over 4.2 min. Analytes were detected on a triple quadrupole tandem mass spectrometer by multiple reaction monitoring mode. The method was validated according to the European Medicine Agency guideline for the selectivity, linearity, and lower limit of detection, precision and accuracy, matrix effects, extraction recovery, carryover, dilution integrity, and stability over a concentration range of 3.0–1000 ng/ml for all analytes. The validated method was applied to real clinical samples of patients treated with one of the drugs. Therefore, we can conclude that our method is suitable for therapeutic drug monitoring of direct oral anticoagulants.
    Type of Medium: Online Resource
    ISSN: 1615-9306 , 1615-9314
    URL: Issue
    URL: Article
    DOI: 10.1002/jssc.v46.13
    DOI: 10.1002/jssc.202300084
    RVK:
    VA 5450
    Language: English
    Publisher: Wiley
    Publication Date: 2023
    detail.hit.zdb_id: 2047990-6
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