title: A sensitive assay for ZD1839 (Iressa) in human plasma by liquid-liquid extraction and high performance liquid chromatography with mass spectrometric detection: validation and use in Phase I clinical trials.
abstract: A specific and sensitive high performance liquid chromatography method for the quantitative determination of ZD1839 ('Iressa') concentrations in treated healthy volunteers and patients with cancer has been developed and validated. Plasma samples (0.5 ml) were extracted, at basic pH, with methyl-t-butyl ether using deuterated ZD1839 as an internal standard. The extracts were chromatographed on an Inertsil ODS3 column eluted with acetonitrile/ammonium acetate and ZD1839 and the internal standard quantified by mass spectrometric detection. The method was validated with respect to linearity, selectivity, precision, accuracy, limit of quantification (LOQ), recovery and stability. The precision and accuracy of the assay were good and the LOQ was 0.5 ng/ml. The assay has been successfully applied to a number of clinical and pharmacokinetic studies and been shown to be robust and reliable during routine use.
authors.affiliation: Drug Metabolism and Pharmacokinetics Department, AstraZeneca, Mereside, Alderley Park, Macclesfield, UK. helen.k.jones@astrazeneca.com
authors.forename: Helen K
authors.initials: HK
authors.lastname: Jones
authors.forename: L E
authors.initials: LE
authors.lastname: Stafford
authors.forename: H C
authors.initials: HC
authors.lastname: Swaisland
authors.forename: R
authors.initials: R
authors.lastname: Payne
mesh_terms: D000970:Antineoplastic Agents / Q000097:blood*; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D017321:Clinical Trials, Phase I as Topic; D004355:Drug Stability; D000077156:Gefitinib; D006801:Humans; D013058:Mass Spectrometry / Q000379:methods*; D011799:Quinazolines / Q000097:blood*; D015203:Reproducibility of Results
chemical_list: D000970:Antineoplastic Agents; D011799:Quinazolines; D000077156:Gefitinib