Pharmacokinetic Assessment of Rottlerin from Mallotus philippensis Using a Highly Sensitive Liquid Chromatography–Tandem Mass Spectrometry-Based Bioanalytical Method
| Autor: | Deepak Sharma, Bhavna Vij, Shreyans K. Jain, Abhishek Gour, Nivedita Bhardwaj, Gurdarshan Singh, Utpal Nandi, Diksha Manhas, Kuhu Sharma |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Bioanalysis
Chromatography biology General Chemical Engineering food and beverages General Chemistry biology.organism_classification Article Highly sensitive chemistry.chemical_compound Chemistry chemistry Pharmacokinetics Liquid chromatography–mass spectrometry Mallotus philippensis Rottlerin QD1-999 |
| Zdroj: | ACS Omega, Vol 6, Iss 48, Pp 32637-32646 (2021) ACS Omega |
| ISSN: | 2470-1343 |
| Popis: | Rottlerin is a key bioactive phytoconstituent present in the pericarp of Mallotus philippensis. It shows promising multifaceted pharmacological actions against cancer. However, there is hardly any report for the quantification of rottlerin in the biological matrix and on its pharmacokinetic behavior. Therefore, we aimed in the present study to assess selective in vitro ADME properties and in vivo pharmacokinetics of isolated and characterized rottlerin using a newly developed and validated liquid chromatography–tandem mass spectrometry-based highly sensitive bioanalytical method. The method was found to be simple (mobile phase and analytical column), sensitive (1.9 ng/mL), and rapid (run time of 2.5 min). All the validation parameters were within the acceptable criteria of the United States Food and Drug Administration’s bioanalytical method validation guideline. The method was found to be very useful to assess lipophilicity, plasma stability, metabolic stability, plasma protein binding of rottlerin, as well as its oral and intravenous pharmacokinetics in mice. Rottlerin showed a number of drug-like pharmacokinetic properties (in vitro). Moreover, it displayed an excellent half-life (>2 h) and oral bioavailability (>35%) as compared to other members of natural phenolics. The present study is the first-time report of in vitro ADME properties and in vivo preclinical pharmacokinetics of rottlerin. The generated information is very much useful for its further development as a phytotherapeutics toward cancer therapy. |
| Databáze: | OpenAIRE |
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