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.
Kojima
J
J
Tokyo Research Laboratories, Kowa Company Ltd., Higashimurayama, Japan.
Fujino
H
H
Yosimura
M
M
Morikawa
H
H
Kimata
H
H
D000818:Animals; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D004285:Dogs; D006801:Humans; D006877:Hydroxamic Acids / Q000737:chemistry; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000097:blood*; D007783:Lactones / Q000097:blood*; D011804:Quinolines / Q000097:blood* / Q000737:chemistry; D051381:Rats; D012015:Reference Standards; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013056:Spectrophotometry, Ultraviolet
D006877:Hydroxamic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007783:Lactones; D011804:Quinolines; C108475:pitavastatin