Detection of landiolol using high-performance liquid chromatography/fluorescence: a blood esterase-sensitive ultra-short-acting beta(1)-receptor antagonist.
Landiolol hydrochloride, a new adrenergic beta(1)-selective antagonist having an ultra-short half-life, is used to prevent tachyarrhythmia during surgery. Since landiolol is thought to be rapidly hydrolyzed to an inactivate metabolite by esterases, quantification of the drug concentration in the blood is impractical. The landiolol concentration in blood was halved within 5 min after blood sampling. This degradation was effectively prevented by pre-treatment with neostigmine (100 microg) in the sampling tube, but not by EDTA pre-treatment, indicating that landiolol could be metabolized by pseudocholinesterase in plasma. After the one-step solid-phase extraction, fluorescence detection of landiolol reduced chromatographic background signals and then improved assay sensitivity to the lower limit of 10 ng/ml in blood; this reproducible approach yielded coefficient variation of less than 6%. The blood concentration-time profile of landiolol hydrochloride in patients of the present investigation afforded more practical assessment than previously reported studies, thus improving accuracy and facilitating detailed pharmacokinetic study in relation to the pharmacological action of drug.
Suno
Manabu
M
Department of Hospital Pharmacy & Pharmacology, Asahikawa Medical College, Asahikawa 078-8510, Japan.
Kunisawa
Takayuki
T
Yamagishi
Akio
A
Ono
Takashi
T
Yamamoto
Joe
J
Yamada
Takehiro
T
Tasaki
Yoshikazu
Y
Shimizu
Keiko
K
Iwasaki
Hiroshi
H
Matsubara
Kazuo
K
D058671:Adrenergic beta-1 Receptor Antagonists; D000319:Adrenergic beta-Antagonists / Q000097:blood* / Q000493:pharmacokinetics; D000328:Adult; D000368:Aged; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D004950:Esterases / Q000097:blood / Q000378:metabolism*; D006207:Half-Life; D006801:Humans; D008875:Middle Aged; D009025:Morpholines / Q000097:blood* / Q000493:pharmacokinetics; D013050:Spectrometry, Fluorescence / Q000379:methods*; D014508:Urea / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics
D058671:Adrenergic beta-1 Receptor Antagonists; D000319:Adrenergic beta-Antagonists; D009025:Morpholines; C077049:landiolol; D014508:Urea; D004950:Esterases