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

Abstract

<jats:p>2,4,6-trihydroxy-3-geranylacetophenone (tHGA) is a bioactive compound that shows excellent anti-inflammatory properties. However, its pharmacokinetics and metabolism have yet to be evaluated. In this study, a sensitive LC-HRMS method was developed and validated to quantify tHGA in rat plasma. The method showed good linearity (0.5–80 ng/mL). The accuracy and precision were within 10%. Pharmacokinetic investigations were performed on three groups of six rats. The first two groups were given oral administrations of unformulated and liposome-encapsulated tHGA, respectively, while the third group received intraperitoneal administration of liposome-encapsulated tHGA. 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 and formulated tHGA, Cmax values were 5.4 and 14.5 ng/mL, tmax values were 0.25 h for both, t1/2 values were 6.9 and 6.6 h, and AUC0–24 values were 17.6 and 40.7 ng/mL·h, respectively. The liposomal formulation improved the relative oral bioavailability of tHGA from 9.1% to 21.0% which was a 2.3-fold increment. Further, a total of 12 metabolites were detected and structurally characterized. The metabolites were mainly products of oxidation and glucuronide conjugation.</jats:p>

What is the role of current mass spectrometry in pharmaceutical analysis?

“…A hybrid QqQ linear ion‐trap is a less employed mass analyzer (Tanner et al, 2019). To date, LC‐HRMS is starting to be used for the pharmacokinetic studies of small molecules, for example, LC coupled with quadrupole in tandem with Orbitrap (Alkhateeb et al, 2020; Park et al, 2021; Qian et al, 2022; Wang, Wang, et al, 2019). The number of publications on this topic has been rising every year.…”

Phloroglucinol and Its Derivatives: Antimicrobial Properties toward Microbial Pathogens

“…A variety of nanoparticle carriers, including liposomes, lipidic carriers, micelles, polymeric materials, dendrimers, nanosuspensions, and nanoemulsions, have been used as controlled drug delivery vehicle systems . To date, polymeric (e.g., chitosan, starch, phytoglycogen, and alginate), lipid, liposome, and γ-cyclodextrin materials have been employed for the encapsulation of phloroglucinol in nanocomplex forms as therapeutic drugs. − Bai et al loaded phlorotannin into whey protein isolate–chitosan oligosaccharide nanocomplexes to increase antioxidant and anti-inflammatory effects. Recently, phloroglucinol was encapsulated into chitosan in the form of nanoparticles (CSNPs) and demonstrated promising antibiofilm activity on C. albicans and bacterial mono- and dual-species biofilms (Figure B).…”

Pharmacological Properties of 2,4,6-Trihydroxy-3-Geranyl Acetophenone and the Underlying Signaling Pathways: Progress and Prospects

“…Taken together, these computational findings strongly validate that tHGA is a safe drug candidate that has the potential to be further developed as a modern medication for treating various diseases. It is important to note that findings from a pharmacokinetic study on tHGA has demonstrated that the oral bioavailability of tHGA in mice was not high ( Alkhateeb et al, 2020 ). However, liposomal formulation has successfully improved the relative oral bioavailability of tHGA from 9.1 to 21.0% which was a 2.3-fold increment.…”