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  1. Article ; Online: Two Fast GC-MS Methods for the Measurement of Nicotine, Propylene Glycol, Vegetable Glycol, Ethylmaltol, Diacetyl, and Acetylpropionyl in Refill Liquids for E-Cigarettes.

    Dagla, Ioanna / Gikas, Evagelos / Tsarbopoulos, Anthony

    Molecules (Basel, Switzerland)

    2023  Volume 28, Issue 4

    Abstract: The use of e-cigarettes (ECs) has become increasingly popular worldwide, even though scientific results have not established their safety. Diacetyl (DA) and acetylpropionyl (AP), which can be present in ECs, are linked with lung diseases. Ethyl maltol ( ... ...

    Abstract The use of e-cigarettes (ECs) has become increasingly popular worldwide, even though scientific results have not established their safety. Diacetyl (DA) and acetylpropionyl (AP), which can be present in ECs, are linked with lung diseases. Ethyl maltol (EM)-the most commonly used flavoring agent-can be present in toxic concentrations. Until now, there is no methodology for the determination of nicotine, propylene glycol (PG), vegetable glycerin (VG), EM, DA, and acetylpropionyl in e-liquids that can be used as a quality control procedure. Herein, gas chromatography coupled with mass spectrometry (GC-MS) was applied for the development of analytical methodologies for these substances. Two GC-MS methodologies were developed and fully validated, fulfilling the standards for the integration in a routine quality control procedure by manufacturers. As proof of applicability, the methodology was applied for the analysis of several e-liquids. Differences were observed between the labeled and the experimental levels of PG, VG, and nicotine. Three samples contained EM at higher concentrations compared to the other samples, while only one contained DA. These validated methodologies can be used for the quality control analysis of EC liquid samples regarding nicotine, PG, and VG amounts, as well as for the measurement of the EM.
    MeSH term(s) Nicotine/analysis ; Gas Chromatography-Mass Spectrometry ; Vegetables ; Electronic Nicotine Delivery Systems ; Diacetyl ; Propylene Glycol/chemistry ; Glycerol/chemistry
    Chemical Substances Nicotine (6M3C89ZY6R) ; ethyl maltol (L6Q8K29L05) ; Diacetyl (K324J5K4HM) ; Propylene Glycol (6DC9Q167V3) ; Glycerol (PDC6A3C0OX)
    Language English
    Publishing date 2023-02-16
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 1413402-0
    ISSN 1420-3049 ; 1431-5165 ; 1420-3049
    ISSN (online) 1420-3049
    ISSN 1431-5165 ; 1420-3049
    DOI 10.3390/molecules28041902
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Baseline Correction for HPLC Chromatograms by Using Free Open-Source Software

    Kostas Gkountanas / Ioanna Dagla / Evangelos Gikas / Anđelija Malenović / Yannis Dotsikas

    Analytica, Vol 4, Iss 5, Pp 45-

    2023  Volume 53

    Abstract: Chromatograms with overlapping peaks and a baseline rise or upset constitute a great challenge for analysts. Such a case regarding the analysis of bupropion hydrochloride and its 5 impurities in a tablet formulation was used as a model. A baseline ... ...

    Abstract Chromatograms with overlapping peaks and a baseline rise or upset constitute a great challenge for analysts. Such a case regarding the analysis of bupropion hydrochloride and its 5 impurities in a tablet formulation was used as a model. A baseline correction technique for liquid chromatography coupled with diode array detection is described by using Rstudio. The asymmetry least squares (ALS) algorithm was used as implemented in the “baseline” package, with parameters lambda and p set to 4 and 0.05, respectively. Peak deconvolution and subsequent integration and area quantification were accomplished through Fytik software. Chromatographic data from the validation procedure were utilized to demonstrate the feasibility of the suggested method and whether this correction affects the outcome of the validation study. Finally, a robustness study was carried out in order to shed light on the factors that have a more significant influence on the baseline correction, showing the reliability of this procedure through random changes in its parameters.
    Keywords data processing ; peak integration ; baseline correction ; asymmetry least squares algorithm ; experimental design ; robustness testing ; Analytical chemistry ; QD71-142
    Language English
    Publishing date 2023-02-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: A Novel Validated Injectable Colistimethate Sodium Analysis Combining Advanced Chemometrics and Design of Experiments.

    Dagla, Ioanna / Tsarbopoulos, Anthony / Gikas, Evagelos

    Molecules (Basel, Switzerland)

    2021  Volume 26, Issue 6

    Abstract: Colistimethate sodium (CMS) is widely administrated for the treatment of life-threatening infections caused by multidrug-resistant Gram-negative bacteria. Until now, the quality control of CMS formulations has been based on microbiological assays. Herein, ...

    Abstract Colistimethate sodium (CMS) is widely administrated for the treatment of life-threatening infections caused by multidrug-resistant Gram-negative bacteria. Until now, the quality control of CMS formulations has been based on microbiological assays. Herein, an ultra-high-performance liquid chromatography coupled to ultraviolet detector methodology was developed for the quantitation of CMS in injectable formulations. The design of experiments was performed for the optimization of the chromatographic parameters. The chromatographic separation was achieved using a Waters Acquity BEH C
    MeSH term(s) Chromatography, High Pressure Liquid/methods ; Colistin/administration & dosage ; Colistin/analogs & derivatives ; Colistin/pharmacology ; Drug Compounding/methods ; Drug Contamination/prevention & control ; Limit of Detection ; Principal Component Analysis/methods ; Quality Control ; Spectrophotometry, Ultraviolet/methods
    Chemical Substances colistinmethanesulfonic acid (DL2R53P963) ; Colistin (Z67X93HJG1)
    Language English
    Publishing date 2021-03-11
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 1413402-0
    ISSN 1420-3049 ; 1431-5165 ; 1420-3049
    ISSN (online) 1420-3049
    ISSN 1431-5165 ; 1420-3049
    DOI 10.3390/molecules26061546
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Colistimethate Acidic Hydrolysis Revisited: Arrhenius Equation Modeling Using UPLC-QToF MS.

    Dagla, Ioanna / Tsarbopoulos, Anthony / Gikas, Evagelos

    Molecules (Basel, Switzerland)

    2021  Volume 26, Issue 2

    Abstract: Colistimethate (CMS), the prodrug of polymyxin E (colistin), is an antibiotic widely used as a last-line therapy against multidrug resistant Gram-negative bacteria, but little is known about its pharmacokinetics as its administration has stopped as a ... ...

    Abstract Colistimethate (CMS), the prodrug of polymyxin E (colistin), is an antibiotic widely used as a last-line therapy against multidrug resistant Gram-negative bacteria, but little is known about its pharmacokinetics as its administration has stopped as a result of high neuro- and nephro-toxicity. The measurement of CMS levels in patients' biological fluids is of great importance in order to find the optimal dose regimen reducing the drug toxicity. Until now, CMS assay methods are based on the indirect determination after its hydrolysis to colistin (CS). Herein, the aim is to find the optimal conditions for the complete hydrolysis of CMS to CS. The reaction was studied at accelerated conditions: 40 °C, 50 °C, and 60 °C, and the results were evaluated by assessing the Arrhenius equation and computation employing the Tenua software. A validated analytical methodology based on ultra-performance liquid chromatography (UPLC) coupled to a hybrid quadrupole time of flight (QToF) instrument is developed for the simultaneous measurement of CMS and CS. The current methodology resulted in complete hydrolysis, in contrast with the previously reported one.
    MeSH term(s) Chromatography, High Pressure Liquid ; Colistin/analogs & derivatives ; Colistin/pharmacokinetics ; Female ; Humans ; Hydrolysis ; Male ; Mass Spectrometry ; Middle Aged ; Models, Biological ; Prodrugs/pharmacokinetics
    Chemical Substances Prodrugs ; colistinmethanesulfonic acid (DL2R53P963) ; Colistin (Z67X93HJG1)
    Language English
    Publishing date 2021-01-16
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 1413402-0
    ISSN 1420-3049 ; 1431-5165 ; 1420-3049
    ISSN (online) 1420-3049
    ISSN 1431-5165 ; 1420-3049
    DOI 10.3390/molecules26020447
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Colistimethate Acidic Hydrolysis Revisited

    Ioanna Dagla / Anthony Tsarbopoulos / Evagelos Gikas

    Molecules, Vol 26, Iss 2, p

    Arrhenius Equation Modeling Using UPLC-QToF MS

    2021  Volume 447

    Abstract: Colistimethate (CMS), the prodrug of polymyxin E (colistin), is an antibiotic widely used as a last-line therapy against multidrug resistant Gram-negative bacteria, but little is known about its pharmacokinetics as its administration has stopped as a ... ...

    Abstract Colistimethate (CMS), the prodrug of polymyxin E (colistin), is an antibiotic widely used as a last-line therapy against multidrug resistant Gram-negative bacteria, but little is known about its pharmacokinetics as its administration has stopped as a result of high neuro- and nephro-toxicity. The measurement of CMS levels in patients’ biological fluids is of great importance in order to find the optimal dose regimen reducing the drug toxicity. Until now, CMS assay methods are based on the indirect determination after its hydrolysis to colistin (CS). Herein, the aim is to find the optimal conditions for the complete hydrolysis of CMS to CS. The reaction was studied at accelerated conditions: 40 °C, 50 °C, and 60 °C, and the results were evaluated by assessing the Arrhenius equation and computation employing the Tenua software. A validated analytical methodology based on ultra-performance liquid chromatography (UPLC) coupled to a hybrid quadrupole time of flight (QToF) instrument is developed for the simultaneous measurement of CMS and CS. The current methodology resulted in complete hydrolysis, in contrast with the previously reported one.
    Keywords colistimethate ; stability ; Arrhenius ; assay ; LC-MS ; Organic chemistry ; QD241-441
    Subject code 621
    Language English
    Publishing date 2021-01-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  6. Article ; Online: A Novel Validated Injectable Colistimethate Sodium Analysis Combining Advanced Chemometrics and Design of Experiments

    Ioanna Dagla / Anthony Tsarbopoulos / Evagelos Gikas

    Molecules, Vol 26, Iss 1546, p

    2021  Volume 1546

    Abstract: Colistimethate sodium (CMS) is widely administrated for the treatment of life-threatening infections caused by multidrug-resistant Gram-negative bacteria. Until now, the quality control of CMS formulations has been based on microbiological assays. Herein, ...

    Abstract Colistimethate sodium (CMS) is widely administrated for the treatment of life-threatening infections caused by multidrug-resistant Gram-negative bacteria. Until now, the quality control of CMS formulations has been based on microbiological assays. Herein, an ultra-high-performance liquid chromatography coupled to ultraviolet detector methodology was developed for the quantitation of CMS in injectable formulations. The design of experiments was performed for the optimization of the chromatographic parameters. The chromatographic separation was achieved using a Waters Acquity BEH C 8 column employing gradient elution with a mobile phase consisting of (A) 0.001 M aq. ammonium formate and (B) methanol/acetonitrile 79/21 ( v / v ). CMS compounds were detected at 214 nm. In all, 23 univariate linear-regression models were constructed to measure CMS compounds separately, and one partial least-square regression (PLSr) model constructed to assess the total CMS amount in formulations. The method was validated over the range 100–220 μg mL −1 . The developed methodology was employed to analyze several batches of CMS injectable formulations that were also compared against a reference batch employing a Principal Component Analysis, similarity and distance measures, heatmaps and the structural similarity index. The methodology was based on freely available software in order to be readily available for the pharmaceutical industry.
    Keywords colistimethate ; UPLC–UV ; multivariate analysis ; pharmaceutical formulations ; quality control ; partial least square regression ; Organic chemistry ; QD241-441
    Subject code 621
    Language English
    Publishing date 2021-03-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  7. Article ; Online: Design of experiments guided multivariate calibration for the quantitation of injectable colistimethate sodium by ultra performance liquid chromatography - High resolution mass spectrometry.

    Dagla, Ioanna / Tsarbopoulos, Anthony / Gikas, Evagelos

    Talanta

    2020  Volume 220, Page(s) 121406

    Abstract: Colistimethate sodium (CMS) is a widely administrated old-generation prodrug for the treatment of the life-threatening infections caused by multi-resistant Gram-negative bacteria. Until now, the quality control procedure of the CMS commercial products is ...

    Abstract Colistimethate sodium (CMS) is a widely administrated old-generation prodrug for the treatment of the life-threatening infections caused by multi-resistant Gram-negative bacteria. Until now, the quality control procedure of the CMS commercial products is based on microbiological assays. The aim of the study is the development of a chemical analysis methodology based on liquid chromatography - mass spectrometry (LC-MS) that could be used for the quality control of CMS products. The careful optimization of the LC and QToF-MS parameters was deemed crucial, as CMS is known to be a very complex mixture. Thus, a two stage Design of Experiments (DoE) pipeline has been followed, aiming towards the separation of the mixture components. According to the DoE results, a baseline-resolved chromatogram revealing more than 20 compounds was achieved. The separation was performed using a Waters Acquity BEH C8 column employing gradient elution. The mobile phase consisted of aq. ammonium formate 0.005 M (pH 6) (solvent A) and methanol/acetonitrile 79/21 (v/v) (solvent B). A second optimization experiment for the MS signal was employed in order to achieve maximum sensitivity. The singly charged signals were monitored for the validation in the positive ion mode. The calibration curve range was 50-110 μg mL
    MeSH term(s) Calibration ; Chromatography, High Pressure Liquid ; Chromatography, Liquid ; Colistin/analogs & derivatives ; Gas Chromatography-Mass Spectrometry ; Mass Spectrometry
    Chemical Substances colistinmethanesulfonic acid (DL2R53P963) ; Colistin (Z67X93HJG1)
    Language English
    Publishing date 2020-07-19
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 1500969-5
    ISSN 1873-3573 ; 0039-9140
    ISSN (online) 1873-3573
    ISSN 0039-9140
    DOI 10.1016/j.talanta.2020.121406
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article: Design of experiments guided multivariate calibration for the quantitation of injectable colistimethate sodium by ultra performance liquid chromatography – High resolution mass spectrometry

    Dagla, Ioanna / Tsarbopoulos, Anthony / Gikas, Evagelos

    Talanta. 2020 Dec. 01, v. 220

    2020  

    Abstract: Colistimethate sodium (CMS) is a widely administrated old-generation prodrug for the treatment of the life-threatening infections caused by multi-resistant Gram-negative bacteria. Until now, the quality control procedure of the CMS commercial products is ...

    Abstract Colistimethate sodium (CMS) is a widely administrated old-generation prodrug for the treatment of the life-threatening infections caused by multi-resistant Gram-negative bacteria. Until now, the quality control procedure of the CMS commercial products is based on microbiological assays. The aim of the study is the development of a chemical analysis methodology based on liquid chromatography - mass spectrometry (LC-MS) that could be used for the quality control of CMS products. The careful optimization of the LC and QToF-MS parameters was deemed crucial, as CMS is known to be a very complex mixture. Thus, a two stage Design of Experiments (DoE) pipeline has been followed, aiming towards the separation of the mixture components. According to the DoE results, a baseline-resolved chromatogram revealing more than 20 compounds was achieved. The separation was performed using a Waters Acquity BEH C8 column employing gradient elution. The mobile phase consisted of aq. ammonium formate 0.005 M (pH 6) (solvent A) and methanol/acetonitrile 79/21 (v/v) (solvent B). A second optimization experiment for the MS signal was employed in order to achieve maximum sensitivity. The singly charged signals were monitored for the validation in the positive ion mode. The calibration curve range was 50–110 μg mL⁻¹, corresponding to the 80–120% of the nominal CMS amount in the commercial products. Due to the complexity of the CMS chromatograms and the corresponding spectrum of each chromatographic peak, untargeted and targeted approaches were performed employing the MZmine software. Furthermore, apart from the classical univariate statistical analysis, partial least squares regression (PLS-R) model was also employed, as the variables were more than the observations. The developed methodology has been employed to analyze several batches and inconsistences have been discovered.
    Keywords Gram-negative bacteria ; acetonitrile ; ammonium ; chemical analysis ; computer software ; experimental design ; formates ; least squares ; mass spectrometry ; methanol ; models ; pH ; quality control ; sodium ; solvents ; ultra-performance liquid chromatography
    Language English
    Dates of publication 2020-1201
    Publishing place Elsevier B.V.
    Document type Article
    ZDB-ID 1500969-5
    ISSN 1873-3573 ; 0039-9140
    ISSN (online) 1873-3573
    ISSN 0039-9140
    DOI 10.1016/j.talanta.2020.121406
    Database NAL-Catalogue (AGRICOLA)

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  9. Article: Effect of Supplementation with Olive Leaf Extract Enriched with Oleuropein on the Metabolome and Redox Status of Athletes' Blood and Urine-A Metabolomic Approach.

    Lemonakis, Nikolaos / Mougios, Vassilis / Halabalaki, Maria / Dagla, Ioanna / Tsarbopoulos, Anthony / Skaltsounis, Alexios-Leandros / Gikas, Evagelos

    Metabolites

    2022  Volume 12, Issue 2

    Abstract: Oleuropein (OE) is a secoiridoid glycoside occurring mostly in the Oleaceae family and presenting several pharmacological properties, including hypolipidemic and antioxidant properties. Based on these, several dietary supplements containing olive leaf ... ...

    Abstract Oleuropein (OE) is a secoiridoid glycoside occurring mostly in the Oleaceae family and presenting several pharmacological properties, including hypolipidemic and antioxidant properties. Based on these, several dietary supplements containing olive leaf extracts enriched with OE are commercially available in many countries. The current study aimed to examine the effect of supplementation with such an extract on the serum and urine metabolome of young healthy male athletes. For this purpose, applying a randomized, balanced, double-blind study, nine young, healthy males (physical education students) received either a commercially prepared extract or placebo for one week, followed by a two-week washout period; then, they were subsequently dosed with the alternate scheme (crossover design). Urine and serum samples were analyzed using UHPLC-HRMS, followed by evaluation with several multivariate methods of data analysis. The data were interpreted using a multilevel metabolomic approach (multilevel-sPLSDA) as it was found to be the most efficient approach for the study design. Metabolic pathway analysis of the most affected metabolites revealed that tryptophan and acylcarnitine's biochemistries were most influenced. Furthermore, several metabolites connected to indole metabolism were detected, which may indicate enhanced serotonin turnover. Phenylethylamine and related metabolites, as well as estrone, were connected to enhanced performance. In addition, possible changes to the lipidemic profile and the blood and urine redox statuses were investigated.
    Language English
    Publishing date 2022-02-20
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2662251-8
    ISSN 2218-1989
    ISSN 2218-1989
    DOI 10.3390/metabo12020195
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: Analytical methodologies used for the determination of colistin in biological fluids. Is it still a challenge?

    Dagla, Ioanna / Karkoula, Evangelia / Baira, Eirini / Tsarbopoulos, Anthony / Gikas, Evagelos

    Journal of pharmaceutical and biomedical analysis

    2018  Volume 164, Page(s) 777–788

    Abstract: Colistin is a multicomponent polypeptide antibiotic consisting mainly of colistin A and colistin B, produced by selected strains of Bacillus polymyxa var. Colistinus. Only recently, the prodrug of colistin, colistimethate sodium, is widely used as last ... ...

    Abstract Colistin is a multicomponent polypeptide antibiotic consisting mainly of colistin A and colistin B, produced by selected strains of Bacillus polymyxa var. Colistinus. Only recently, the prodrug of colistin, colistimethate sodium, is widely used as last resort antibiotic for infections caused by resistant gram-negative bacteria. Colistin having been discovered several years ago, has not subjected to the drug development and regulatory approval processes that are applied today. However, pharmacological and pharmacokinetic information are necessary for its optimal use thus, during the last decades several studies are carried out in order to shed light on this issue. In the current review, the analytical methodologies of colistin assessment in biological material are summarized and the analytical challenges are critically discussed and critical aspects of the determinations such as the method of detection, the sample pretreatment methodology etc. are compared. Furthermore, critical quality aspects of the assessment methodologies such as the sensitivity of the currently developed methodologies are presented. Lastly, some future trends that should be incorporated in the determination pipeline of modern drugs are suggested.
    MeSH term(s) Animals ; Anti-Bacterial Agents/analysis ; Biological Products/analysis ; Chemical Fractionation/methods ; Chromatography/instrumentation ; Chromatography/methods ; Colistin/analogs & derivatives ; Colistin/analysis ; Humans ; Mass Spectrometry/instrumentation ; Mass Spectrometry/methods ; Paenibacillus polymyxa ; Prodrugs/analysis
    Chemical Substances Anti-Bacterial Agents ; Biological Products ; Prodrugs ; colistinmethanesulfonic acid (DL2R53P963) ; Colistin (Z67X93HJG1)
    Language English
    Publishing date 2018-11-19
    Publishing country England
    Document type Comparative Study ; Journal Article ; Review
    ZDB-ID 604917-5
    ISSN 1873-264X ; 0731-7085
    ISSN (online) 1873-264X
    ISSN 0731-7085
    DOI 10.1016/j.jpba.2018.11.044
    Database MEDical Literature Analysis and Retrieval System OnLINE

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