LC/MS/MS analysis of vesnarinone and its principal metabolites in plasma and urine

An LC/MS/MS assay was developed and successfully used to quantitate vesnari none and its principal metabolites (OPC-8230, OPC-18136, and OPC-18137) in human plasma and urine. Samples were pre-treated with liquid-solid extracti on followed by simultaneous monitoring of primary and daughter ions which w ere used for the identification and quantitation of the analytes on LC/MS/M S. This assay offers advantages of specificity, speed and greater sensitivi ty over the previously developed HPLC-UV assay. The lower limit of quantita tion is 500 ng ml(-1) for vesnarinone and 20 ng ml(-1) for OPC-8230, OPC-18 137, and OPC-18136 in plasma. Methodology is similar for the estimation of these analytes in urine with the lower limit of quantitation being 500 ng m l(-1) for vesnarinone and 100 ng ml(-1) for each metabolite. Ascorbic acid was added to stabilize the analytes from degradation. This LC/MS/MS method was developed to overcome many practical problems associated with the HPLC method. The LC/MS/MS method offers the flexibility of analyzing additional metabolites and changing the linearity range to accommodate the differences in linear range (200-10 000 ng ml(-1) for vesnarinone and 20-1000 for meta bolites) for the analytes. (C) 1999 Elsevier Science B.V. All rights reserv ed.