title: Development and validation of a sensitive liquid chromatography/tandem mass spectrometry method for the determination of exemestane in human plasma.
abstract: Exemestane, irreversible steroidal aromatase inhibitor, acts as a false substrate for aromatase enzyme and significantly lowers circulating estrogen concentrations in postmenopausal women with hormone-sensitive breast cancer. A sensitive bioanalytical method was developed and validated to study pharmacokinetics of exemestane. The method was based on liquid-liquid extraction of exemestane with methyl t-butyl ether followed by reversed-phase liquid chromatography. Positive electrospray ionization tandem mass spectrometry in multiple reaction monitoring mode was applied for detection of exemestane. Anastrozole was used as internal standard. Calibration curve, fitted to 1/x² weighted linear regression model, was linear in the range of 0.1-40.0 ng/mL. Intra-run precision and accuracy were 1.80-3.17% and 103.4-111.5%, respectively. Inter-run precision and accuracy measured within 3 days were 3.37-4.19% and 101.8-109.6%, respectively. Extraction recoveries of exemestane and internal standard were 79.7-86.2% and 82.9-83.6%, respectively. The method was fully validated and may be applied to pharmacokinetic studies in humans after a single dose administration of 25mg exemestane tablets.
authors.affiliation: Pharmaceutical Research Institute, Pharmacology Department, Warsaw, Poland.
authors.forename: Hanna
authors.initials: H
authors.lastname: Ksycińska
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Buś-Kwaśnik
authors.forename: Anna
authors.initials: A
authors.lastname: Szlagowska
authors.forename: Piotr J
authors.initials: PJ
authors.lastname: Rudzki
mesh_terms: D000077384:Anastrozole; D000730:Androstadienes / Q000097:blood*; D000970:Antineoplastic Agents / Q000097:blood; D002853:Chromatography, Liquid / Q000379:methods*; D006801:Humans; D016014:Linear Models; D009570:Nitriles / Q000097:blood; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D021241:Spectrometry, Mass, Electrospray Ionization; D053719:Tandem Mass Spectrometry / Q000379:methods*; D014230:Triazoles / Q000097:blood
chemical_list: D000730:Androstadienes; D000970:Antineoplastic Agents; D009570:Nitriles; D014230:Triazoles; D000077384:Anastrozole; C056516:exemestane