title: Development of a novel LC-MS/MS method for the determination of letosteine in human plasma and its application on pharmacokinetic studies.
abstract: Letosteine has been found to be effective in treating patients with chronic bronchopneumopathies in clinical practice. To provide robust support for its pharmacokinetic and clinical studies, a rapid and sensitive method based on liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) was developed and validated for the analysis of letosteine in plasma samples. After protein precipitation, the plasma samples were separated on a reversed-phase C(18) column in less than 1.5 min. The LC-MS/MS system was performed in the positive ion multiple-reaction-monitoring (MRM) mode to produce intensive product ions of m/z 280.1→160.0 for letosteine and m/z 248.1→121.1 for the internal standard, tinidazole. The method was found to have excellent linearity (r ≥ 0.9974), precision (RSD ≤ 5.83%), extraction recovery (71.8-73.0%) and stability (RE, -8.45% to 9.03%) over a concentration range of 0.1140-152.0 μgL(-1). Compared to the previous published radioactive method, LC-MS/MS method showed many advantages including shorter analysis time, simpler preparation procedure, increased sensitivity as well as lower safety risks. In addition, this method was successfully applied to study the pharmacokinetics of letosteine following a single and multiple dose oral administration in Chinese healthy volunteers.
authors.affiliation: Institute of Clinical pharmacology, Department of Pharmacology, Tongji Medical College of Huazhong University of Science and Technology, Wuhan, Hubei 430030, People's Republic of China.
authors.forename: Xinxia
authors.initials: X
authors.lastname: Liu
authors.forename: Heng
authors.initials: H
authors.lastname: Zheng
authors.forename: Wei
authors.initials: W
authors.lastname: Tang
authors.forename: Zhenyu
authors.initials: Z
authors.lastname: Qian
authors.forename: Yinsong
authors.initials: Y
authors.lastname: Zhu
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.forename: Shiying
authors.initials: S
authors.lastname: Yuan
authors.forename: Xin
authors.initials: X
authors.lastname: Wen
authors.forename: Cuiling
authors.initials: C
authors.lastname: Cao
authors.forename: Hui
authors.initials: H
authors.lastname: Chen
mesh_terms: D000704:Analysis of Variance; D056148:Chromatography, Reverse-Phase / Q000379:methods*; D004355:Drug Stability; D005260:Female; D006801:Humans; D016018:Least-Squares Analysis; D008297:Male; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D053719:Tandem Mass Spectrometry / Q000379:methods*; D053778:Thiazolidines / Q000097:blood* / Q000493:pharmacokinetics*
chemical_list: D053778:Thiazolidines; C018578:letosteine