UTILIZATION OF HIGH RESOLUTION TANDEM MASS SPECTROMETRY FOR DETERMINATION OF 59 ANALOGUES OF PDE5 INHIBITORS AS POSSIBLE ADULTERANTS OF BOTANICAL-BASED DIETARY SUPPLEMENTS

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F60461373%3A22330%2F17%3A43914135" target="_blank" >RIV/60461373:22330/17:43914135 - isvavai.cz</a>

Výsledek na webu

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DOI - Digital Object Identifier

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Jazyk výsledku

angličtina

Název v původním jazyce

UTILIZATION OF HIGH RESOLUTION TANDEM MASS SPECTROMETRY FOR DETERMINATION OF 59 ANALOGUES OF PDE5 INHIBITORS AS POSSIBLE ADULTERANTS OF BOTANICAL-BASED DIETARY SUPPLEMENTS

Popis výsledku v původním jazyce

The popularity of natural preparations supporting the sexual potency have significantly increased during the recent years, what also has led to an increase of illegal use of various phosphodiesterase type 5 inhibitors (PDE-5) in these herbal-based sexual performance enhancement products. These fraudulent practices can be very dangerous for consumers, due to the fact that a presence of nondeclared biologically active may result in interferences with other medicaments used by users. The main contraindications are with antihypertensives, antidepresives, sedatives, anxiolytics, and can lead to a stroke and/or heart attack. Although erectile function supporting dietary supplements are frequently consumed, there is still lack of proper analytical methods usable for its sensitive chemical analysis. In this study, rapid ultra-high pressure liquid chromatography coupled with high resolution tandem mass spectrometry (U-HPLC-HRMS/MS) method has been developed for simultaneous determination of 59 phosphodiesterase type 5 inhibitors, which can be used for the treatment of erectile dysfunction. Within the development of a new sensitive method for analysis of 59 PDE-5 inhibitors, both sample preparation procedure and separation/detection conditions were optimized. Extraction efficiency of particular extraction solvents, the influence of different mobile phase additives on target analytes separation, as well as the impact of various settings of mass analyzer on sensitivity of detection were examined. The data were collected in a full MS/data dependent MS/MS acquisition mode (full MS?dd-MS/MS). Before the U-HPLC-HRMS/MS method was used for analysis of real life samples, a comprehensive validation was performed. Repeatability with overall relative standard deviation (RSD) was &lt;8 % (N=6), measured at 1.0 and 5.0 ?g/g, limits of quantification were in the range 0.25 ? 0.05 ?g/g and the recovery was 71-90 %. U-HPLC-HRMS/MS method for PDE5 inhibitors was successfully applied to 64 real samples, which were continuously collected in cooperation with the Czech Agriculture and Food Inspection Authority (CAFIA) during 2009 and 2015 as a part of official control activities. As can be seen on Figure 1, the ultra-high resolution of orbitrap mass analyzer (70 000 FWHM at m/z 200) enabled measurement of ions with very high mass accuracy, when the mass detecting error usually does not exceed 2 ppm and confirmation of fragment ions acquired during the parallel MS/MS experiment. The assessment of a compliance of fragmentation pattern of suspicious analyte with those in the ?inhousecreated? MS/MS library (i.e. MS/MS mass spectra of PDE-5 inhibitor standards acquired within the method development) could be carried out. From the 64 samples analyzed, 10 samples were found to be positive for at least 4 up to 9 analytes. Altogether, 20 different analytes were identified in tested samples. Sildenafil, imidasosagatriazinone, sildenafil-N-oxide, and propoxyphenylsildenafil represented the most frequent PDE-5 inhibitors. In addition to that, the acquired U-HPLC-HRMS/MS fingerprints were demonstrated to serve as a powerful tool for revealing of other types of possible frauds in products labeling. Retrospective mining of markers of herbs declared on dietary supplements packaging allowed to assess the trueness of declaration (i.e. medical herbs composition), what is very useful for efficient fight with food fraud.

Název v anglickém jazyce

UTILIZATION OF HIGH RESOLUTION TANDEM MASS SPECTROMETRY FOR DETERMINATION OF 59 ANALOGUES OF PDE5 INHIBITORS AS POSSIBLE ADULTERANTS OF BOTANICAL-BASED DIETARY SUPPLEMENTS

Popis výsledku anglicky

The popularity of natural preparations supporting the sexual potency have significantly increased during the recent years, what also has led to an increase of illegal use of various phosphodiesterase type 5 inhibitors (PDE-5) in these herbal-based sexual performance enhancement products. These fraudulent practices can be very dangerous for consumers, due to the fact that a presence of nondeclared biologically active may result in interferences with other medicaments used by users. The main contraindications are with antihypertensives, antidepresives, sedatives, anxiolytics, and can lead to a stroke and/or heart attack. Although erectile function supporting dietary supplements are frequently consumed, there is still lack of proper analytical methods usable for its sensitive chemical analysis. In this study, rapid ultra-high pressure liquid chromatography coupled with high resolution tandem mass spectrometry (U-HPLC-HRMS/MS) method has been developed for simultaneous determination of 59 phosphodiesterase type 5 inhibitors, which can be used for the treatment of erectile dysfunction. Within the development of a new sensitive method for analysis of 59 PDE-5 inhibitors, both sample preparation procedure and separation/detection conditions were optimized. Extraction efficiency of particular extraction solvents, the influence of different mobile phase additives on target analytes separation, as well as the impact of various settings of mass analyzer on sensitivity of detection were examined. The data were collected in a full MS/data dependent MS/MS acquisition mode (full MS?dd-MS/MS). Before the U-HPLC-HRMS/MS method was used for analysis of real life samples, a comprehensive validation was performed. Repeatability with overall relative standard deviation (RSD) was &lt;8 % (N=6), measured at 1.0 and 5.0 ?g/g, limits of quantification were in the range 0.25 ? 0.05 ?g/g and the recovery was 71-90 %. U-HPLC-HRMS/MS method for PDE5 inhibitors was successfully applied to 64 real samples, which were continuously collected in cooperation with the Czech Agriculture and Food Inspection Authority (CAFIA) during 2009 and 2015 as a part of official control activities. As can be seen on Figure 1, the ultra-high resolution of orbitrap mass analyzer (70 000 FWHM at m/z 200) enabled measurement of ions with very high mass accuracy, when the mass detecting error usually does not exceed 2 ppm and confirmation of fragment ions acquired during the parallel MS/MS experiment. The assessment of a compliance of fragmentation pattern of suspicious analyte with those in the ?inhousecreated? MS/MS library (i.e. MS/MS mass spectra of PDE-5 inhibitor standards acquired within the method development) could be carried out. From the 64 samples analyzed, 10 samples were found to be positive for at least 4 up to 9 analytes. Altogether, 20 different analytes were identified in tested samples. Sildenafil, imidasosagatriazinone, sildenafil-N-oxide, and propoxyphenylsildenafil represented the most frequent PDE-5 inhibitors. In addition to that, the acquired U-HPLC-HRMS/MS fingerprints were demonstrated to serve as a powerful tool for revealing of other types of possible frauds in products labeling. Retrospective mining of markers of herbs declared on dietary supplements packaging allowed to assess the trueness of declaration (i.e. medical herbs composition), what is very useful for efficient fight with food fraud.

Druh

D - Stať ve sborníku

CEP obor

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OECD FORD obor

30107 - Medicinal chemistry

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2017

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název statě ve sborníku

FOODINTEGRITY 2017 CONFERENCE

ISBN

978-88-941066-5-7

ISSN

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e-ISSN

neuvedeno

Počet stran výsledku

2

Strana od-do

235-236

Název nakladatele

Barilla

Místo vydání

Parma

Místo konání akce

Parma

Datum konání akce

10. 5. 2017

Typ akce podle státní příslušnosti

WRD - Celosvětová akce

Kód UT WoS článku

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