title: Enantioselective and sensitive determination of carvedilol in human plasma using chiral stationary-phase column and reverse-phase liquid chromatography with tandem mass spectrometry.
abstract: A liquid chromatography-tandem mass spectrometry method to quantify carvedilol enantiomers in human plasma was developed and validated as a measure of compliance in clinical research. Carvedilol enantiomers were extracted from human serum (0.5 mL) via liquid-liquid extraction with methyl tert-butyl ether (2.5 mL). Carvedilol-related compound C served as the internal standard. The analyte and internal standard were separated on a Sino-Chiral AD column (150 × 4.6mm, 5 μm, amylose tris-3,5-dimethylphenylcarbamate coated on silica-gel) using isocratic elution with mobile phases of methanol, water and diethylamine (94:6:0.01, v/v). The total run-time was 10.5 min. Carvedilol enantiomers were quantified using a triple quadrupole mass spectrometer operated in multiple-reaction-monitoring mode using positive electrospray ionisation. The mass transitions monitored for quantitation were carvedilol (m/z 407→222) and carvedilol-related compound C (m/z 497→222). The limits of quantification for the S- and R-carvedilol enantiomers in plasma were both 0.08 ng/mL. The method was validated in the linear range of 0.08-50 ng/mL with acceptable inter- and intra-assay precision and accuracy and stability suitable for routine laboratory practice. The method was successfully applied to samples taken from research volunteers treated with carvedilol sustained-release tablet 18 mg. Cmax and AUClast were 9.1 ± 5.1 ng/mL and 59.4 ± 39.6 ng h/mL for R-carvedilol, 4.0 ± 2.3 ng/mL and 24.7 ±15.0 ng h/mL for S-carvedilol, respectively. tmax and t1/2 were 4.6 ± 1.9h and 9.6 ± 4.5h for R-carvedilol, and 4.7 ± 1.0 h and 10.7 ± 5.7 h, respectively.
authors.affiliation: The Key Laboratory of Clinical Trial Research of Cardiovascular Drugs, Fu Wai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China. Electronic address: jiangjuanjuan_80@163.com.
authors.forename: Juanjuan
authors.initials: J
authors.lastname: Jiang
authors.affiliation: The Key Laboratory of Clinical Trial Research of Cardiovascular Drugs, Fu Wai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China. Electronic address: tianlei0807@hotmail.com.
authors.forename: Lei
authors.initials: L
authors.lastname: Tian
authors.affiliation: The Key Laboratory of Clinical Trial Research of Cardiovascular Drugs, Fu Wai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China. Electronic address: hylhyl@foxmail.com.
authors.forename: Yiling
authors.initials: Y
authors.lastname: Huang
authors.affiliation: The Key Laboratory of Clinical Trial Research of Cardiovascular Drugs, Fu Wai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China. Electronic address: YanY926@hotmail.com.
authors.forename: Yan
authors.initials: Y
authors.lastname: Yan
authors.affiliation: The Key Laboratory of Clinical Trial Research of Cardiovascular Drugs, Fu Wai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China. Electronic address: Liyishi@public3.bta.net.cn.
authors.forename: Yishi
authors.initials: Y
authors.lastname: Li
mesh_terms: D002227:Carbazoles / Q000097:blood* / Q000737:chemistry* / Q000493:pharmacokinetics; D000077261:Carvedilol; D056148:Chromatography, Reverse-Phase / Q000295:instrumentation* / Q000379:methods*; D004355:Drug Stability; D006801:Humans; D016018:Least-Squares Analysis; D008297:Male; D011412:Propanolamines / Q000097:blood* / Q000737:chemistry* / Q000493:pharmacokinetics; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013237:Stereoisomerism; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D002227:Carbazoles; D011412:Propanolamines; D000077261:Carvedilol
keywords: Carvedilol; Chiral column; Enantiomer; Human plasma; LC–MS/MS; Method validation