SH-1242, a novel inhibitor of
heat shock protein 90 (HSP90), is a synthetic analog of
deguelin: It was previously reported that the treatment of
SH-1242 led to a strong suppression of
hypoxia-mediated
retinal neovascularization and vascular leakage in diabetic retinas by inhibiting the
hypoxia-induced upregulation of expression in
hypoxia-inducible factor 1α (HIF-1ɑ) and
vascular endothelial growth factor (
VEGF). In this study, an analytical method for the quantification of
SH-1242 in biological samples from rats and mice was developed/validated for application in pharmacokinetic studies.
SH-1242 and
deguelin, an internal standard of the assay, in plasma samples from the rodents were extracted with
methanol containing 0.1%
formic acid and analyzed at m/z transition values of 368.9→151.0 and 395.0→213.0, respectively. The method was validated in terms of accuracy, precision, dilution, matrix effects, recovery, and stability and shown to comply with validation guidelines when it was used in the concentration ranges of 1-1000 ng/mL for rat plasma and of 2-1000 ng/mL for mouse plasma.
SH-1242 levels in plasma samples were readily determined using the developed method for up to 480 min after the
intravenous administration of 0.1 mg/kg
SH-1242 to rats and for up to 120 min to mice. These findings suggested that the current method was practical and reliable for pharmacokinetic studies on
SH-1242 in preclinical animal species.