Home
Resources
Publications
Pharmacokinetics of Rac Inhibitor EHop-016 in Mice by Ultra-Performance Liquid Chromatography Tandem Mass Spectrometry

Pharmacokinetics of Rac Inhibitor EHop-016 in Mice by Ultra-Performance Liquid Chromatography Tandem Mass Spectrometry

Tessa Humphries-Bickley, Linette Castillo-Pichardo, Francheska Corujo-Carro, Jorge Duconge, Eliud Hernandez-O'Farrill, Cornelis Vlaar, Jose F Rodriguez-Orengo, Luis Cubano, Suranganie Dharmawardhane

J Chromatogr B Analyt Technol Biomed Life Sci. 2015 Feb 15;981-982:19-26.

PMID: 25594952

Abstract:

The Rho GTPase Rac is an important regulator of cancer cell migration and invasion; processes required for metastatic progression. We previously characterized the small molecule EHop-016 as a novel Rac inhibitor in metastatic breast cancer cells and recently found that EHop-016 was effective at reducing tumor growth in nude mice at 25 mg/kg bodyweight (BW). The purpose of this study was to compare the pharmacokinetics and bioavailability of EHop-016 at different dosages in a single dose input scheme (10, 20 and 40 mg/kg BW) following intraperitoneal (IP) and oral gavage (PO) administration to nude mice. We developed and validated a rapid and sensitive method for the quantitation of EHop-016 in mouse plasma by ultra high performance liquid chromatography coupled with electrospray ionization tandem mass spectrometry (UPLC/MS/MS). Separation was carried out on an Agilent Poroshell 120 EC-C18 column (3.0 mm × 50 mm) using organic and aqueous mobile phases. EHop-016 was identified from its accurate mass and retention time from the acquired full-scan chromatogram and quantified by its peak area. The validated method was linear (R(2)>0.995) over the range of 5-1000 ng/mL (1/x(2) weighting). Pharmacokinetic parameters were obtained by non-compartmental analysis using WinNonlin. The area under the curve (AUC₀-∞) ranged from 328 to 1869 ng h/mL and 133-487 ng h/mL for IP and PO dosing, respectively. The elimination half-life (t₁/₂) ranged from 3.8-5.7 h to 3.4-26.8 h for IP and PO dosing, respectively. For both IP and PO administration, the AUC₀-∞values were proportional to the tested doses demonstrating linear PK profiles. The relative bioavailability of EHop-016 after oral gavage administration ranged from 26% to 40%. These results support further preclinical evaluation of EHop-016 as a new anti-cancer therapy.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP1380432325	EHop-016		1380432-32-5	Price

As a specialist in analytical chemical Products, Alfa Chemistry offers consumers a wealth of raw materials and a full range of technologies and services.

QUICK LINKS

HEADQUARTERS

Tel:

Fax:

Email: