Hideki Kimata

Simultaneous determination of NK-104 and its lactone in biological samples by column-switching high-performance liquid chromatography with ultraviolet detection

A simple and sensitive column-switching HPLC method has been developed for the simultaneous determination of NK-104 (HMG-CoA reductase inhibitor) and its lactone in human and dog plasma. Plasma sample was extracted with methyl tert-butyl ether and then the extract was subjected to methylation with diazomethane to prevent the mutual conversion between NK-104 and its lactone. The extract was injected into the column-switching HPLC system. The calibration curves of NK-104 and NK-104 lactone were linear over the ranges 0.5 to 100 ng/ml for human plasma samples and 0.5 to 500 ng/ml for dog plasma, respectively. The intra-day and inter-day C.V. values of these analytes were less than 13.3%. The intra-day and inter-day accuracies of these analytes were between -14.0 and 6.5%. The proposed method has been applied to plasma samples obtained after oral administration of a single 2 mg dose of NK-104 to volunteers.

Metabolism of nipradilol by liver homogenates from different species. I. Comparative studies on the denitration of nipradilol and other organic nitrates

Nipradilol (NP) was metabolized mainly in liver and denitrated and/or hydroxylated metabolites were formed. NP was not metabolized in heart or lung, and was stable in blood. Denitration of NP was catalysed mainly by glutathione-dependent organic nitrate reductase in liver cytosol, and the hydroxylation was catalysed by liver-microsomal enzymes. Denitration activity for NP was far lower than that for nitroglycerol and isosorbide dinitrate with liver homogenates of several animal species. A marked species difference was found in the denitration activity for NP; dog liver was especially low compared with rabbit, rat and mouse liver.