Page 153 - أبحاث كلية الصيدلة 2016-2020

Appendix 2020 Publications

Molecules

Pharmacokinetics and Metabolism of Liposome-Encapsulated 2,4,6-
Trihydroxygeranylacetophenone in Rats Using High-Resolution Orbitrap Liquid

Chromatography Mass Spectrometry
Yamen Alkhateeb, Qais Bashir Jarrar, Faridah Abas, Yaya Rukayadi,Chau Ling

Tham, Yuen Kah Hay and Khozirah Shaari

2,4,6-trihydroxy-3-geranylacetophenone (tHGA) is a bioactive compound that
showsexcellent anti-inflammatory properties. However, its pharmacokinetics and metabolism
have yet tobe evaluated. In this study, a sensitive LC-HRMS method was developed and
validated to quantifytHGA in rat plasma. The method showed good linearity (0.5–80 ng/mL).
The accuracy and precisionwere within 10%. Pharmacokinetic investigations were performed
on three groups of six rats. The firsttwo groups were given oral administrations of
unformulated and liposome-encapsulated tHGA,respectively, while the third group received
intraperitoneal administration of liposome-encapsulatedtHGA. The maximum concentration
(Cmax), the time required to reach Cmax(tmax), elimination half-life(t1/2) and area under
curve (AUC0–24) values for intraperitoneal administration were 54.6 ng/mL,1.5 h, 6.7 h, and
193.9 ng/mL·h, respectively. For the oral administration of unformulated andformulated
tHGA, Cmaxvalues were 5.4 and 14.5 ng/mL, tmaxvalues were 0.25 h for both,
t1/2valueswere 6.9 and 6.6 h, and AUC0–24values were 17.6 and 40.7 ng/mL·h, respectively.
The liposomalformulation improved the relative oral bioavailability of tHGA from 9.1% to
21.0% which was a2.3-fold increment. Further, a total of 12 metabolites were detected and
structurally characterized.The metabolites were mainly products of oxidation and glucuronide
conjugation.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7412073/pdf/molecules-25-03069.pdf

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