A Validated HPLC-PDA-HRMS Method to Investigate the Biological Stability and Metabolism of Antiparasitic Triterpenic Esters
Pentacyclic triterpenes (PTs) are commonly found in medicinal plants with well-known antiparasitic effects. Previous research on C-3 and C-27 triterpenic esters showed effective and selective in vitro antiparasitic activities and in vivo effectiveness by parenteral routes. The aim of this study was...
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| Natura: | Articolo |
| Lingua: | English |
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MDPI AG
2021-11-01
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| Serie: | Molecules |
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| Accesso online: | https://www.mdpi.com/1420-3049/26/23/7154 |
| _version_ | 1827674804909506560 |
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| author | Laura Schioppa Fanta Fall Sergio Ortiz Jacques H. Poupaert Joelle Quetin-Leclercq |
| author_facet | Laura Schioppa Fanta Fall Sergio Ortiz Jacques H. Poupaert Joelle Quetin-Leclercq |
| author_sort | Laura Schioppa |
| collection | DOAJ |
| description | Pentacyclic triterpenes (PTs) are commonly found in medicinal plants with well-known antiparasitic effects. Previous research on C-3 and C-27 triterpenic esters showed effective and selective in vitro antiparasitic activities and in vivo effectiveness by parenteral routes. The aim of this study was to determine triterpenic esters’ stability in different biological-like media and the main microsomal degradation products. An HPLC-PDA method was developed and validated to simultaneously analyze and quantify bioactive triterpenic esters in methanol (LOQ: 2.5 and 1.25–100 µg/mL) and plasma (LOQ: 5–125 µg/mL). Overall, both triterpenic esters showed a stable profile in aqueous and buffered solutions as well as in entire plasma, suggesting gaining access to the ester function is difficult for plasma enzymes. Conversely, after 1 h, 30% esters degradation in acidic media was observed with potential different hydrolysis mechanisms. C-3 (15 and 150 µM) and C-27 esters (150 µM) showed a relatively low hepatic microsomal metabolism (<23%) after 1 h, which was significantly higher in the lowest concentration of C-27 esters (15 µM) (>40% degradation). Metabolic HPLC-PDA-HRMS studies suggested hydrolysis, hydroxylation, dehydration, <i>O</i>-methylation, hydroxylation and/or the reduction of hydrolyzed derivatives, depending on the concentration and the position of the ester link. Further permeability and absorption studies are required to better define triterpenic esters pharmacokinetic and specific formulations designed to increase their oral bioavailability. |
| first_indexed | 2024-03-10T04:48:22Z |
| format | Article |
| id | doaj.art-703d4f5ee6e64e5fa5aa7c1e39d4edb1 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-10T04:48:22Z |
| publishDate | 2021-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-703d4f5ee6e64e5fa5aa7c1e39d4edb12023-11-23T02:48:14ZengMDPI AGMolecules1420-30492021-11-012623715410.3390/molecules26237154A Validated HPLC-PDA-HRMS Method to Investigate the Biological Stability and Metabolism of Antiparasitic Triterpenic EstersLaura Schioppa0Fanta Fall1Sergio Ortiz2Jacques H. Poupaert3Joelle Quetin-Leclercq4Pharmacognosy Laboratory, Louvain Drug Research Institute (LDRI), Université Catholique de Louvain (UCLouvain), Avenue E. Mounier, B1 72.03, B-1200 Brussels, BelgiumPharmacognosy Laboratory, Louvain Drug Research Institute (LDRI), Université Catholique de Louvain (UCLouvain), Avenue E. Mounier, B1 72.03, B-1200 Brussels, BelgiumPharmacognosy Laboratory, Louvain Drug Research Institute (LDRI), Université Catholique de Louvain (UCLouvain), Avenue E. Mounier, B1 72.03, B-1200 Brussels, BelgiumMedicinal Chemistry Research Group (CMFA), Louvain Drug Research Institute (LDRI), Université Catholique de Louvain (UCLouvain), Avenue E. Mounier, B1 72.04, B-1200 Brussels, BelgiumPharmacognosy Laboratory, Louvain Drug Research Institute (LDRI), Université Catholique de Louvain (UCLouvain), Avenue E. Mounier, B1 72.03, B-1200 Brussels, BelgiumPentacyclic triterpenes (PTs) are commonly found in medicinal plants with well-known antiparasitic effects. Previous research on C-3 and C-27 triterpenic esters showed effective and selective in vitro antiparasitic activities and in vivo effectiveness by parenteral routes. The aim of this study was to determine triterpenic esters’ stability in different biological-like media and the main microsomal degradation products. An HPLC-PDA method was developed and validated to simultaneously analyze and quantify bioactive triterpenic esters in methanol (LOQ: 2.5 and 1.25–100 µg/mL) and plasma (LOQ: 5–125 µg/mL). Overall, both triterpenic esters showed a stable profile in aqueous and buffered solutions as well as in entire plasma, suggesting gaining access to the ester function is difficult for plasma enzymes. Conversely, after 1 h, 30% esters degradation in acidic media was observed with potential different hydrolysis mechanisms. C-3 (15 and 150 µM) and C-27 esters (150 µM) showed a relatively low hepatic microsomal metabolism (<23%) after 1 h, which was significantly higher in the lowest concentration of C-27 esters (15 µM) (>40% degradation). Metabolic HPLC-PDA-HRMS studies suggested hydrolysis, hydroxylation, dehydration, <i>O</i>-methylation, hydroxylation and/or the reduction of hydrolyzed derivatives, depending on the concentration and the position of the ester link. Further permeability and absorption studies are required to better define triterpenic esters pharmacokinetic and specific formulations designed to increase their oral bioavailability.https://www.mdpi.com/1420-3049/26/23/7154triterpenesstabilityHPLC-PDA/MSin vitro stabilitymetabolomicsparasitic infections |
| spellingShingle | Laura Schioppa Fanta Fall Sergio Ortiz Jacques H. Poupaert Joelle Quetin-Leclercq A Validated HPLC-PDA-HRMS Method to Investigate the Biological Stability and Metabolism of Antiparasitic Triterpenic Esters Molecules triterpenes stability HPLC-PDA/MS in vitro stability metabolomics parasitic infections |
| title | A Validated HPLC-PDA-HRMS Method to Investigate the Biological Stability and Metabolism of Antiparasitic Triterpenic Esters |
| title_full | A Validated HPLC-PDA-HRMS Method to Investigate the Biological Stability and Metabolism of Antiparasitic Triterpenic Esters |
| title_fullStr | A Validated HPLC-PDA-HRMS Method to Investigate the Biological Stability and Metabolism of Antiparasitic Triterpenic Esters |
| title_full_unstemmed | A Validated HPLC-PDA-HRMS Method to Investigate the Biological Stability and Metabolism of Antiparasitic Triterpenic Esters |
| title_short | A Validated HPLC-PDA-HRMS Method to Investigate the Biological Stability and Metabolism of Antiparasitic Triterpenic Esters |
| title_sort | validated hplc pda hrms method to investigate the biological stability and metabolism of antiparasitic triterpenic esters |
| topic | triterpenes stability HPLC-PDA/MS in vitro stability metabolomics parasitic infections |
| url | https://www.mdpi.com/1420-3049/26/23/7154 |
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