Bioavailability, plasma protein binding and metabolic stability studies of a ALDH2 activator, alda-1, using a validated LC-ESI-MS/MS method in rat plasma

摘要: Alda-1 is an activator of the enzyme ALDH2. It has been suggested as a novel therapeutic for cardiovascular implications such myocardial infarction, coronary bypass surgery, heart transplantation, peripheral artery disease, ischemia reperfusion injury, angina and alcoholic cardiomyopathy. Despite its widespread experimental use, no reports are available on pharmacokinetics or bioanalytical quantification. In present study, simple, precise reliable LC-ESI-MS/MS method developed validated first time quantification alda-1 in plasma. was analyzed C18 column using methanol 0.1% formic acid (60 : 40, v/v) mobile phase at flow rate 0.7 mL min−1. The found to be linear within concentration range 1–500 ng mL−1. intra- inter-day precision accuracy were acceptable limits. For time, preclinical oral intravenous conducted. rapidly absorbed, high clearance poorly bioavailable compound rats. Its plasma protein binding 82–86%. view new regulatory guidelines, incurred sample reanalysis also performed all samples 15% mean value. From vitro microsomal incubation studies, it extraction compound. data presented here provide important information support vivo efficacy would helpful further development agent synthesis analogs with better systemic exposure disposition properties.