title: Simultaneous quantification of carvedilol and its metabolites in rat plasma by ultra performance liquid chromatography tandem mass spectrometry and pharmacokinetic application.
abstract: A rapid-resolution ultra high-performance liquid chromatography-tandem mass spectrometry separation method (UPLC-MS/MS) was developed for the simultaneous determination of carvedilol, and its three metabolites: 4'-hydroxyphenyl-carvedilol, 5'-hydroxyphenyl-carvedilol, o-desmethyl-carvedilol. The effective UPLC-MS/MS separation of the examined compounds was applied on an Acquity BEH C18 column (2.1 mm × 5 0 mm, 1.7 μm particle size) column with a gradient mobile phase system. The analysis was performed in less than 6 min with a flow rate of 0.4 mL/min. The assay was validated over concentration ranges of 0.500-100 ng/mL for carvedilol and 0.0500-10.0 ng/mL for its three metabolites. Intra- and inter-assay precision values for replicate quality control samples were within 11.4% for all analytes during the assay validation. Mean quality control accuracy values were within ±11.5% of nominal values for all analytes. Assay recoveries were high (>91%) and internal standard normalized matrix effects were minimal. The four analytes were stable in rat plasma for at least 24h at room temperature, 89 days at -20 °C and -80 °C, and following at least five freeze-thaw cycles. The validated assay was successfully applied to the quantification of carvedilol and its pharmacologically active metabolites in rat pharmacokinetic study. The accurate and simple method we developed could be applied to human pharmacokinetic study in the near future.
authors.affiliation: Institute of Molecular Pharmacology and Toxicology, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325000, China.
authors.forename: Junwei
authors.initials: J
authors.lastname: Li
authors.affiliation: Institute of Molecular Pharmacology and Toxicology, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325000, China.
authors.forename: Li
authors.initials: L
authors.lastname: Wang
authors.affiliation: The Laboratory of Clinical Pharmacy, The People's Hospital of Lishui, Lishui, Zhejiang 323000, China.
authors.forename: Shuanghu
authors.initials: S
authors.lastname: Wang
authors.affiliation: Institute of Molecular Pharmacology and Toxicology, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325000, China.
authors.forename: Mengchun
authors.initials: M
authors.lastname: Chen
authors.affiliation: Institute of Molecular Pharmacology and Toxicology, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325000, China.
authors.forename: Ermin
authors.initials: E
authors.lastname: Gu
authors.affiliation: Institute of Molecular Pharmacology and Toxicology, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325000, China.
authors.forename: Guoxin
authors.initials: G
authors.lastname: Hu
authors.affiliation: The 2nd Affiliated Hospital of Wenzhou Medical University, Wenzhou Medical University, Wenzhou, Zhejiang 325000, China. Electronic address: raygee0828@163.com.
authors.forename: Renshan
authors.initials: R
authors.lastname: Ge
mesh_terms: D000818:Animals; D000959:Antihypertensive Agents / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*; D002227:Carbazoles / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*; D000077261:Carvedilol; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D008297:Male; D015394:Molecular Structure; D011412:Propanolamines / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D000959:Antihypertensive Agents; D002227:Carbazoles; D011412:Propanolamines; D000077261:Carvedilol
keywords: Assay; Carvedilol; Metabolite; UPLC–MS/MS