Affiliations 

  • 1 MedChem Herbal Research Group, Faculty of Pharmacy, Universiti Teknologi MARA, Selangor Campus, Puncak Alam, 42300 Selangor, Malaysia
  • 2 MedChem Herbal Research Group, Faculty of Pharmacy, Universiti Teknologi MARA, Selangor Campus, Puncak Alam, 42300 Selangor, Malaysia; PLS Core, Universiti Teknologi MARA, Shah Alam, 40450 Selangor, Malaysia. Electronic address: choo715@puncakalam.uitm.edu.my
PMID: 28869873 DOI: 10.1016/j.jchromb.2017.08.037

Abstract

Bruceines D and E are quassinoids from seeds of Brucea javanica (L.) Merr. exhibiting hypoglycemia effect. The crude drug is used as a traditional medicine by diabetes patients. The aim of this study is to understand the bioavailability and pharmacokinetics of both the bruceines D & E. A rapid and sensitive HPLC-MS/MS method was developed and validated for the quantification of both quassinoids, bruceines D & E in rat plasma. Both the bruceines D & E were separated with the Zorbax SBC-18 column with gradient elution and mobile phase system of acetonitrile and deionized water with 0.1% formic acid at a flow rate of 0.5mL/min. Analytes were detected in multiple reaction monitoring (MRM) mode with electrospray positive ionization. The quassinoids, namely bruceines D & E were detected with transitions of m/z 411.2→393.2 and m/z 395.2→377.2, respectively. Another quassinoid, eurycomanone was used as the internal standard with transition of m/z 409.2→391.2. The method was validated and conformed to the regulatory requirements. The validated method was applied to pharmacokinetic and bioavailability studies in rats. The pharmacokinetic study indicated both bruceine D and E were rapidly absorbed into the circulation system and reached its peak concentration at 0.54±0.34h and 0.66±0.30h, respectively. Bruceine E was eliminated slower than Bruceine D with t1/2 value almost increased two-fold compared to Bruceine D. In conclusion, a rapid, selective and sensitive HPLC-MS/MS method was developed for the simultaneous determination of both the bruceines D and E in rat plasma. Both bruceines D and E displayed poor oral bioavailability.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.