title: Determination of landiolol, an ultra-short-acting β₁-receptor antagonist, in human plasma by liquid chromatography-tandem mass spectrometry.
abstract: A method for the determination of landiolol, an ultra-short-acting β₁-adrenoreceptor antagonist, in human plasma has been developed and validated. With the addition of pyridostigmine bromide to stabilize landiolol in the blood/plasma samples, and bisoprolol as internal standard, plasma samples were subjected to liquid-liquid extraction with diethyl ether:dicholoromethane (60:40, v/v) prior to assay by liquid chromatography-tandem mass spectrometry. Separation was performed on a TC-C₁₈ column (150 mm × 4.6 mm, 5 μm) using a mobile phase of methanol:10 mM ammonium acetate containing 1% formic acid (65:35, v/v) in a run time of 3.5 min. Detection involved electrospray ionization in the positive ion mode followed by multiple reaction monitoring of the precursor-to-product ion transitions of landiolol at m/z 510.1→157.2 and bisoprolol at m/z 326.3→116.1. The method was linear over the concentration range 0.5-500 ng/ml with a lower limit of quantitation of 0.5 ng/ml. Intra- and inter-day precisions (as relative standard deviation, RSD) were <4.4% and <10.0%, respectively, with accuracy (as relative error, RE) <10.0%. The method was successfully applied to a clinical pharmacokinetic study involving a continuous infusion of landiolol hydrochloride to healthy Chinese volunteers.
authors.affiliation: Clinical Pharmacology Center, Institute for Translational Medicine, Norman Bethune First Hospital, Jilin University, 519 Dongminzhu Street, Changchun 130061, PR China.
authors.forename: Qun
authors.initials: Q
authors.lastname: He
authors.forename: Meiyun
authors.initials: M
authors.lastname: Shi
authors.forename: Xidong
authors.initials: X
authors.lastname: Liu
authors.forename: Yantong
authors.initials: Y
authors.lastname: Sun
authors.forename: Lianghai
authors.initials: L
authors.lastname: Hu
authors.forename: Yan
authors.initials: Y
authors.lastname: Yang
authors.forename: J Paul
authors.initials: JP
authors.lastname: Fawcett
authors.forename: Jingkai
authors.initials: J
authors.lastname: Gu
authors.forename: Limei
authors.initials: L
authors.lastname: Zhao
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000097:blood* / Q000493:pharmacokinetics; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D006801:Humans; D057230:Limit of Detection; D009025:Morpholines / Q000097:blood* / Q000493:pharmacokinetics; D018342:Receptors, Adrenergic, beta-1 / Q000187:drug effects*; D015203:Reproducibility of Results; D053719:Tandem Mass Spectrometry / Q000379:methods*; D014508:Urea / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics
chemical_list: D000319:Adrenergic beta-Antagonists; D009025:Morpholines; D018342:Receptors, Adrenergic, beta-1; C077049:landiolol; D014508:Urea