title: LC-MS determination and relative bioavailability of doxazosin mesylate tablets in healthy Chinese male volunteers.
abstract: This study aims to develop a standard protocol for the relative bioavailability testing of doxazosin mesylate tablets. For this purpose, a simple rapid and selective LC-MS method using a single quadrupole mass spectrometer was developed and validated to determine the concentration of doxazosin mesylate in human plasma. Using this method, we carried out a study of relative bioavailability. N-Hexylane-tertiary butyl methyl ether (1:1, v/v) was used to extract doxazosin mesylate and terazosin (internal standard, I.S.) from an alkaline plasma sample. LC separation was performed on a Thermo Hypersil-Hypurity C18 (5 microm, 150 mm x 2.1mm) using aqueous solution (20 mmol/l ammonium acetate, pH 4.28), methanol and acetonitrile (55:10:35, v/v/v) as the mobile phase. The retention time of doxazosin and the internal standard was 2.7 and 1.8 min, respectively. Quadrupole MS detection was done by monitoring at m/z 388 (M+1) corresponding to doxazosin mesylate and at m/z 452 (M+1) for I.S. The assay method described above showed acceptable precision, accuracy, linearity, stability, and specificity. The bioavailability of doxazosin mesylate was evaluated in 12 healthy Chinese male volunteers. The following pharmacokinetic parameters were elucidated after administering a single dose of 4 mg doxazosin. The area under the plasma concentration versus time curve from time 0 to 72 h (AUC(0-72 h)) 743.4+/-149.5 ngh/ml; peak plasma concentration (C(max)) 47.66 ng/ml; time to C(max) (T(max)) 3.0+/-1.0 h; and elimination half-life (t(1/2)) 18-20 h. The method was successfully used to determine the relative bioavailability of doxazosin mesylate.
authors.affiliation: State Key Laboratory, Department of Pharmaceutical Analysis, China Pharmaceutical University, Nanjing 210009, PR China.
authors.forename: Ning
authors.initials: N
authors.lastname: Ma
authors.forename: Wenying
authors.initials: W
authors.lastname: Liu
authors.forename: Huande
authors.initials: H
authors.lastname: Li
authors.forename: Benmei
authors.initials: B
authors.lastname: Chen
authors.forename: Yungui
authors.initials: Y
authors.lastname: Zhu
authors.forename: Xiaolei
authors.initials: X
authors.lastname: Liu
authors.forename: Feng
authors.initials: F
authors.lastname: Wang
authors.forename: Daxiong
authors.initials: D
authors.lastname: Xiang
authors.forename: Bikui
authors.initials: B
authors.lastname: Zhang
mesh_terms: D000317:Adrenergic alpha-Antagonists / Q000008:administration & dosage / Q000493:pharmacokinetics*; D000328:Adult; D019540:Area Under Curve; D001682:Biological Availability; D002138:Calibration; D002853:Chromatography, Liquid; D018592:Cross-Over Studies; D017292:Doxazosin / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D005615:Freezing; D006207:Half-Life; D006801:Humans; D008297:Male; D013058:Mass Spectrometry; D012015:Reference Standards; D015203:Reproducibility of Results; D012996:Solutions; D021241:Spectrometry, Mass, Electrospray Ionization; D013607:Tablets; D013810:Therapeutic Equivalency
chemical_list: D000317:Adrenergic alpha-Antagonists; D012996:Solutions; D013607:Tablets; D017292:Doxazosin