Determination of l-(+)-bornesitol, the hypotensive constituent of Hancornia speciosa, in rat plasma by LC-MS/MS and its application on a pharmacokinetic study

Autor: Whocely V. de Castro, Clarissa Feltrin, Luciana N. Moreira, Rodrigo Maia de Pádua, Cláudia Maria Oliveira Simões, Steyner F. Cortes, José Eduardo Gonçalves, Fernão Castro Braga
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Male
0301 basic medicine
Spectrometry
Mass
Electrospray Ionization
Bioanalysis
Bornesitol
Electrospray ionization
Administration
Oral
Biological Availability
RM1-950
Models
Biological
Permeability
Hancornia speciosa
03 medical and health sciences
chemistry.chemical_compound
Rutin
0302 clinical medicine
Pharmacokinetics
Tandem Mass Spectrometry
Oral administration
Animals
Humans
Intestinal Mucosa
Rats
Wistar
Caco-2 cells
Antihypertensive Agents
Chromatography
High Pressure Liquid
Permeability study
Pharmacology
Chromatography
Plant Extracts
Chemistry
Selected reaction monitoring
General Medicine
Rat plasma pharmacokinetic study
Bioavailability
Apocynaceae
030104 developmental biology
Intestinal Absorption
Nonlinear Dynamics
030220 oncology & carcinogenesis
Injections
Intravenous
Therapeutics. Pharmacology
UPLC-ESI-MS/MS
Cyclitols
Zdroj: Biomedicine & Pharmacotherapy, Vol 132, Iss, Pp 110900-(2020)
ISSN: 0753-3322
Popis: Hancornia speciosa is a medicinal plant with proven antihypertensive activity. The cyclitol l -(+)-bornesitol is the main constituent of its leaves and is a potent inhibitor of the angiotensin-converting enzyme. We herein investigated the pharmacokinetic properties of bornesitol administered orally to Wistar rats, as well as bornesitol permeation in Caco-2 cells. Bornesitol was isolated and purified from an ethanol extract of H. speciosa leaves. An ultra-high performance liquid chromatography coupled with electrospray ionization mass spectrometry (UPLC-ESI-MS/MS) method was developed and validated to quantify bornesitol in rat plasma based on Multiple Reaction Monitoring, using pentaerythritol as an internal standard. Pharmacokinetics was evaluated by the administration of single doses via intravenous in bolus (3 mg/kg) and gavage (3, 15 and 25 mg/kg). Bornesitol permeation was assayed in a transwell Caco-2 cells model, tested alone, or combined with rutin, or as a constituent of H. speciosa extract, using a developed and validated UPLC-ESI-MS/MS method. All assayed validation parameters (selectivity, residual effect, matrix effect, linearity, precision, accuracy and stability of analyte in plasma and solution) for the bioanalytical method met the acceptance criteria established by regulatory guidelines. Bornestiol reached peak plasma concentration within approximately 60 min after oral administration with a half-life ranging from 72.15 min to 123.69 min. The peak concentration and area under the concentration-time curve of bornesitol did not rise proportionally with the increasing doses, suggesting a non-linear pharmacokinetics in rats and the oral bioavailability ranged from 28.5%–59.3%. Bornesitol showed low permeability in Caco-2 cells, but the permeability apparently increased when it was administered either combined with rutin or as a constituent of H. speciosa extract. In conclusion, bornesitol was rapidly absorbed after a single oral administration to rats and followed a non-linear pharmacokinetics. The obtained data will be useful to guide further pre-clinical development of bornesitol-containing herbal preparations of H. speciosa as an antihypertensive agent.
Databáze: OpenAIRE
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