title: Detection of landiolol using high-performance liquid chromatography/fluorescence: a blood esterase-sensitive ultra-short-acting beta(1)-receptor antagonist.
abstract: 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.
authors.affiliation: Department of Hospital Pharmacy & Pharmacology, Asahikawa Medical College, Asahikawa 078-8510, Japan.
authors.forename: Manabu
authors.initials: M
authors.lastname: Suno
authors.forename: Takayuki
authors.initials: T
authors.lastname: Kunisawa
authors.forename: Akio
authors.initials: A
authors.lastname: Yamagishi
authors.forename: Takashi
authors.initials: T
authors.lastname: Ono
authors.forename: Joe
authors.initials: J
authors.lastname: Yamamoto
authors.forename: Takehiro
authors.initials: T
authors.lastname: Yamada
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Tasaki
authors.forename: Keiko
authors.initials: K
authors.lastname: Shimizu
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Iwasaki
authors.forename: Kazuo
authors.initials: K
authors.lastname: Matsubara
mesh_terms: 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
chemical_list: D058671:Adrenergic beta-1 Receptor Antagonists; D000319:Adrenergic beta-Antagonists; D009025:Morpholines; C077049:landiolol; D014508:Urea; D004950:Esterases