High-performance liquid chromatographic determination of 3'-hydroxy-5'-(4-isobutyl-1-piperazinyl)benzoxazinorifamycin (KRM-1648) and its deacetyl metabolite in plasma, whole blood, urine and tissue samples in rats.
A reversed-phase high-performance liquid chromatographic method was developed for the determination of 3'-hydroxy-5'-(4-isobutyl-1-piperazinyl)benzoxazinorifamycin (KRM-1648, I), a new rifamycin derivative, and its 25-deacetyl metabolite (KRM-1671, II) in plasma, whole blood, tissues and urine from rats. I and II were coextracted with an internal standard from each sample matrix by solid-phase extraction (Bond Elut). Plasma and urine were directly loaded onto Bond Elut, while whole blood and tissues were homogenized and extracted with methanol or dichloromethane-chloroform prior to Bond Elut extraction. The extracts were chromatographed on Shim-pack CLC-ODS(M) using acetonitrile-0.02 M citrate buffer containing 0.1 M sodium perchlorate (2:1, v/v), and peaks were detected at 643 nm. The validation data showed that the assays for I and II in plasma, whole blood, tissues and urine were selective, accurate and reproducible.
Hosoe
K
K
Biochemical Research Laboratories, Kaneka Corporation, Hyogo, Japan.
Konishi
E
E
Hidaka
T
T
Yamane
T
T
Yamashita
K
K
Ohashi
T
T
D000818:Animals; D000904:Antibiotics, Antitubercular / Q000032:analysis* / Q000097:blood / Q000493:pharmacokinetics / Q000652:urine; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D008297:Male; D051381:Rats; D015203:Reproducibility of Results; D012294:Rifamycins / Q000032:analysis* / Q000097:blood / Q000493:pharmacokinetics / Q000652:urine; D013057:Spectrum Analysis; D014018:Tissue Distribution
D000904:Antibiotics, Antitubercular; D012294:Rifamycins; C068980:KRM 1648; C087647:KRM 1671