High-performance liquid chromatography with chemiluminescence detection of penbutolol and its hydroxylated metabolite in rat plasma.
This paper describes a new method of high-performance liquid chromatography with chemiluminescence detection for the analysis of penbutolol (PB) and its main metabolite, 4-hydroxy penbutolol (4-OH PB) in rat plasma. 4-Dimethylaminosulfonyl-7-(N-chloroformylmethyl-N-methyl) amino-2,1,3-benzoxadiazole (DBD-COCl) was used as a fluorogenic labeling reagent. A mixture of hydrogen peroxide and bis[4-nitro-2-(3,6,9-trioxadecyloxycarbonyl)phenyl]oxalate (TDPO) in acetonitrile was used as a post-column chemiluminogenic reagent. The derivatives of PB and 4-OH PB with DBD-COCI were separated by isocratic effluent with 0.01 M imidazole buffer (pH 7.0)-acetonitrile within 10 min. The detection limits of the proposed method for PB and 4-OH PB were 9.9 and 15 fmol on column, respectively. After intravenous administration of PB in rats, its plasma concentration profiles of PB and 4-OH PB were determined by the proposed method. PB was demonstrated to be rapidly metabolized to 4-OH PB at the same rate as cardiac output.
Funato
K
K
Aventis Pharma Ltd., Kawagoe, Saitama, Japan.
Imai
T
T
Nakashima
K
K
Otagiri
M
M
D000818:Animals; D002138:Calibration; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D006900:Hydroxylation; D007202:Indicators and Reagents; D008163:Luminescent Measurements; D010394:Penbutolol / Q000097:blood*; D051381:Rats; D015203:Reproducibility of Results; D013050:Spectrometry, Fluorescence
D007202:Indicators and Reagents; D010394:Penbutolol