Quantification of lipid modified estrogenic derivative (ESC8) in rat plasma by LC‐MS: application to a pharmacokinetic study

Abstract

A lipid-conjugated, estrogenic derivative molecule, ESC8, compared with other estrogenic molecules, encourages cell death in both ER-positive and ER-negative breast cancer cells. A rapid and highly sensitive assay method has been developed and validated for the estimation of a ESC8 in rat plasma using liquid chromatography coupled with mass spectrometry under positive-ion mode with electrospray ionization. The sample process includes using methanol for precipitation of ESC8 and dextromethorphan (internal standard, IS) from plasma. Chromatographic separation was achieved with methanol-water-formic acid (70:30:0.1% v/v/v) pumped at a flow rate of 0.3mL/min and a C column (50 × 2.1 mm i.d., 1.7 μm particle size) with a total run time of 5 min. The m/z ions monitored were 568.5 and 272.1 for ESC8 and IS, respectively. The lower limit of quantitation achieved was 1.08 ng/mL and linearity was observed from 5 to 500 ng/mL. The intra- and inter-day precisions were <4%. The proposed method was successfully applied to a preliminary pharmacokinetic study of ESC8 liposomal formulation following an intraperitoneal administration of 3.67 mg/kg in rats. The concentrations of ESC8 in plasma were quantifiable up to 36 h. The peak concentration of ESC8 was found to be 110.72 ng/mL, the area under the concentration-time curve was 1625.23ng/mL h and the half-life was 11.72 h.

Glucocorticoid receptor-targeted liposomal delivery system for delivering small molecule ESC8 and anti-miR-Hsp90 gene construct to combat colon cancer

“…Hence, past investigations from our lab have demonstrated that GR, albeit expressed in all cells, can be specifically targeted to cancer cell-associated GR which leads to effective tumor regression. Moreover, cationic lipid formulations of GR-ligand dexamethasone indicated multi-faceted cooperative effects, such as cancer cell-specific anti-proliferative action, EMT reversal, instigation of apoptosis in tumor, drug sensitization with increase in p53 levels, powerful anti-angiogenic action and effective tumor regression in mice [44][45][46][47][48].…”