title: Development and validation of a highly sensitive LC-MS/MS-ESI method for the determination of bicalutamide in mouse plasma: application to a pharmacokinetic study.
abstract: A highly sensitive, rapid assay method has been developed and validated for the estimation of bicalutamide in mouse plasma using liquid chromatography coupled to tandem mass spectrometry with electrospray ionization in the negative-ion mode. The assay procedure involves extraction of bicalutamide and tolbutamide (internal standard, IS) from mouse plasma with a simple protein precipitation method. Chromatographic separation was achieved using an isocratic mobile phase (0.2% formic acid:acetonitrile, 35:65, v/v) at a flow rate of 0.5 mL/min on an Atlantis dC₁₈ column (maintained at 40 ± 1°C) with a total run time of 3.0 min. The MS/MS ion transitions monitored were m/z 428.9 → 254.7 for bicalutamide and m/z 269.0 → 169.6 for IS. Method validation was performed as per FDA guidelines and the results met the acceptance criteria. The lower limit of quantitation achieved was 1.04 ng/mL and the linearity range extended from 1.04 to 1877 ng/mL. The intra- and inter-day precisions were in the ranges of 0.49-4.68 and 2.62-4.15, respectively.
authors.affiliation: Drug Metabolism and Pharmacokinetics, Jubilant Biosys Ltd, Industrial Suburb, Yeshwanthpur, Bangalore 560022, India.
authors.forename: Kuldeep
authors.initials: K
authors.lastname: Sharma
authors.forename: Gopal V
authors.initials: GV
authors.lastname: Pawar
authors.forename: Sanjeev
authors.initials: S
authors.lastname: Giri
authors.forename: Sriram
authors.initials: S
authors.lastname: Rajagopal
authors.forename: Ramesh
authors.initials: R
authors.lastname: Mullangi
mesh_terms: D000813:Anilides / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics; D000818:Animals; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D004355:Drug Stability; D057230:Limit of Detection; D016014:Linear Models; D051379:Mice; D008807:Mice, Inbred BALB C; D009570:Nitriles / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics; D015203:Reproducibility of Results; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods; D053719:Tandem Mass Spectrometry / Q000379:methods*; D014105:Tosyl Compounds / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics
chemical_list: D000813:Anilides; D009570:Nitriles; D014105:Tosyl Compounds; C053541:bicalutamide