title: Quantitative determination of enzalutamide, an anti-prostate cancer drug, in rat plasma using liquid chromatography-tandem mass spectrometry, and its application to a pharmacokinetic study.
abstract: This report details a method using liquid chromatography-tandem mass spectrometry (LC-MS/MS) that allows one to determine the concentration of an atypical anticancer drug, enzalutamide, in rat plasma. Specifically, this method involves the addition of an acetonitrile and bicalutamide (internal standard) solution to plasma samples. Following centrifugation of this mixture, an aliquot of the supernatant was directly injected into the LC-MS/MS system. Separation was achieved using a column packed with octadecylsilica (5 µm, 2.1 × 50 mm) with 10 mM ammonium acetate in acetonitrile as the mobile phase; detection was accomplished using MS/MS by multiple-reaction monitoring via an electrospray ionization source. This method demonstrated a linear standard curve (r = 0.997) over a concentration range of 0.001-1 µg/mL, as well as an intra- and inter-assay precision of 2.7 and 5.1%, respectively, and an accuracy range from 100.8 to 105.6%. The lower limit of quantification was 1.0 ng/mL in 50 μL of rat plasma sample. We also demonstrated that this analytical method could be successfully applied to the pharmacokinetic study of enzalutamide in rats.
authors.affiliation: Graduate School of New Drug Discovery and Development, Chungnam National University, Daejeon, Korea.
authors.forename: Ji-Hye
authors.initials: JH
authors.lastname: Song
authors.forename: Tae-Heon
authors.initials: TH
authors.lastname: Kim
authors.forename: Jong-Woo
authors.initials: JW
authors.lastname: Jung
authors.forename: Nakjeong
authors.initials: N
authors.lastname: Kim
authors.forename: Sung Hoon
authors.initials: SH
authors.lastname: Ahn
authors.forename: Sung-Ook
authors.initials: SO
authors.lastname: Hwang
authors.forename: Nam Sook
authors.initials: NS
authors.lastname: Kang
authors.forename: Sung-Eun
authors.initials: SE
authors.lastname: Yoo
authors.forename: Tae-Sung
authors.initials: TS
authors.lastname: Koo
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics; D001549:Benzamides; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D016014:Linear Models; D008297:Male; D009570:Nitriles; D010669:Phenylthiohydantoin / Q000031:analogs & derivatives* / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics; D011471:Prostatic Neoplasms; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D009570:Nitriles; D010669:Phenylthiohydantoin; C540278:enzalutamide
keywords: LC/MS/MS; bicalutamide; enzalutamide; pharmacokinetics; rat plasma