title: Two complementary liquid chromatography-tandem mass spectrometry (LC-MS/MS) methods to study the excretion and metabolic interaction of edaravone and taurine in rats.
abstract: In this study, two independent and complementary liquid chromatography-tandem mass spectrometry (LC-MS/MS) methods were respectively developed and validated for the determination of edaravone or taurine in rat urine, feces and bile after intravenous administration, using 3-methyl-l-p-tolyl-5-pyrazolone and sulfanilic acid as the internal standards (IS). Edaravone was separated on an Agilent Eclipse Plus C18 column (100×2.1 mm, 3.5 μm) using methanol and water (containing 5 mM ammonium formate and 0.02% formic acid) as mobile phase, while taurine was performed on a Waters Atlantis HILIC Silica column (150×2.1 mm, 3 μm) using acetonitrile and water (containing 5mM ammonium formate and 0.2% formic acid) as mobile phase. The mass analysis was performed in a Triple Quadrupole mass spectrometer via multiple reaction monitoring (MRM) with negative ionization mode. The optimized mass transition ion pairs (m/z) for quantification were 173.1→92.2 and 187.2→106.0 for edaravone and its IS, 124.1→80.0 and 172.0→80.0 for taurine and its IS, respectively. The validated methods have been successfully applied to the excretion and metabolism interaction study of edaravone and taurine in rats after independent intravenous administration and co-administration with a single dose. The results demonstrated that there were no significant alternations on the metabolism and cumulative excretion rate of edaravone and taurine, implying that the proposed combination therapy was pharmacologically viable.
authors.affiliation: Department of Pharmaceutical Analysis, Xuzhou Medical College, Xuzhou, Jiangsu 221004, China; Key Laboratory of New Drug and Clinical Application, Xuzhou Medical College, Xuzhou, Jiangsu 221004, China. Electronic address: tdq993@hotmail.com.
authors.forename: Dao-quan
authors.initials: DQ
authors.lastname: Tang
authors.affiliation: Key Laboratory of New Drug and Clinical Application, Xuzhou Medical College, Xuzhou, Jiangsu 221004, China.
authors.forename: Xiao-xiao
authors.initials: XX
authors.lastname: Zheng
authors.affiliation: Key Laboratory of New Drug and Clinical Application, Xuzhou Medical College, Xuzhou, Jiangsu 221004, China.
authors.forename: Yin-jie
authors.initials: YJ
authors.lastname: Li
authors.affiliation: Key Laboratory of New Drug and Clinical Application, Xuzhou Medical College, Xuzhou, Jiangsu 221004, China.
authors.forename: Ting-ting
authors.initials: TT
authors.lastname: Bian
authors.affiliation: Department of Pharmaceutical Analysis, Xuzhou Medical College, Xuzhou, Jiangsu 221004, China; Key Laboratory of New Drug and Clinical Application, Xuzhou Medical College, Xuzhou, Jiangsu 221004, China.
authors.forename: Yan-yan
authors.initials: YY
authors.lastname: Yu
authors.affiliation: Key Laboratory of New Drug and Clinical Application, Xuzhou Medical College, Xuzhou, Jiangsu 221004, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Du
authors.affiliation: Department of Pharmaceutical Analysis, Xuzhou Medical College, Xuzhou, Jiangsu 221004, China; Key Laboratory of New Drug and Clinical Application, Xuzhou Medical College, Xuzhou, Jiangsu 221004, China.
authors.forename: Dong-zhi
authors.initials: DZ
authors.lastname: Yang
authors.affiliation: Nanjing Yoko Pharmaceutical Co. Ltd, Nanjing, Jiangsu 210046, China. Electronic address: jiangshuishi@yoko-bio.com.
authors.forename: Shui-shi
authors.initials: SS
authors.lastname: Jiang
mesh_terms: D000818:Animals; D000983:Antipyrine / Q000031:analogs & derivatives* / Q000032:analysis / Q000737:chemistry / Q000378:metabolism / Q000493:pharmacokinetics; D001646:Bile / Q000737:chemistry; D002853:Chromatography, Liquid / Q000379:methods*; D004355:Drug Stability; D000077553:Edaravone; D005243:Feces / Q000737:chemistry; D016014:Linear Models; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D053719:Tandem Mass Spectrometry / Q000379:methods*; D013654:Taurine / Q000032:analysis* / Q000737:chemistry / Q000378:metabolism / Q000493:pharmacokinetics*
chemical_list: D013654:Taurine; D000077553:Edaravone; D000983:Antipyrine
keywords: Edaravone; Excretion; LC-MS/MS; Metabolism; Taurine