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HPLC-MS/MS method for bioavailability study of bruceines D & E in rat plasma.

Farahdina Man¹, Chee-Yan Choo²

¹MedChem Herbal Research Group, Faculty of Pharmacy, Universiti Teknologi MARA, Selangor Campus, Puncak Alam, 42300 Selangor, Malaysia.

Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences

|September 5, 2017

Summary

Bruceines D and E from Brucea javanica show potential for diabetes treatment but have poor oral bioavailability. Pharmacokinetic studies reveal rapid absorption but limited systemic exposure for these hypoglycemic quassinoids.

Keywords:

Bioavailability Bruceine D Bruceine E HPLC–MS/MS Pharmacokinetic Quassinoid

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Area of Science:

Pharmacology
Natural Products Chemistry
Analytical Chemistry

Background:

Brucea javanica seeds yield quassinoids, including bruceines D and E, known for their hypoglycemic effects.
Traditional medicine utilizes this crude drug for diabetes management.
Understanding the pharmacokinetic profile and bioavailability of these compounds is crucial for therapeutic development.

Purpose of the Study:

To develop and validate a sensitive analytical method for quantifying bruceines D and E in rat plasma.
To investigate the bioavailability and pharmacokinetic characteristics of bruceines D and E in rats.

Main Methods:

A rapid and sensitive High-Performance Liquid Chromatography-tandem Mass Spectrometry (HPLC-MS/MS) method was established and validated.
The method employed a Zorbax SBC-18 column with gradient elution using acetonitrile and deionized water with formic acid.
Quantification was performed using multiple reaction monitoring (MRM) with electrospray positive ionization.

Main Results:

The validated HPLC-MS/MS method demonstrated high sensitivity and selectivity for simultaneous determination of bruceines D and E.
Pharmacokinetic analysis showed rapid absorption of both compounds, with peak plasma concentrations reached within an hour.
Bruceine E exhibited slower elimination than bruceine D, indicated by a longer half-life. Both compounds displayed poor oral bioavailability.

Conclusions:

A robust HPLC-MS/MS method was successfully developed for the analysis of bruceines D and E in rat plasma.
The study highlights the rapid absorption and differential elimination of bruceines D and E.
Poor oral bioavailability of both bruceines D and E necessitates further research for potential therapeutic applications.