title: Quantitative measurement of 4-hydroxy tamoxifen in human plasma and mammary tumours by combined gas chromatography/negative chemical ionization mass spectrometry.
abstract: A highly sensitive and specific assay was developed for the quantitative measurement of 4-hydroxy tamoxifen (4-OH Tam) at the femtomole level in human plasma and mammary tumours. The drug and deuterated internal standard (4-OH Tam D4) were measured by gas chromatography/negative chemical ionization mass spectrometry with methane as the reactant gas. The two compounds of interest were isolated from the complex biological matrices using a solid-phase extraction procedure with Extrelut 1 columns. Soft operating conditions were required to convert 4-OH Tam to the fluorinated derivatives with pentafluorobenzyl chloride. The mass spectrometer was tuned to monitor the abundant and stable molecular ions at m/z 581 and 585 which were generated in the ion source by an electron capture process. This assay required only 0.5 ml of plasma or 0.5 g of mammary tissue, and the quantification limits of the method were 20 pg ml-1 for the body fluids or 100 pg g-1 for the tissue samples. The very low relative standard deviation and mean percentage error calculated during the different within-day or day-to-day repeatability assays have clearly demonstrated the ruggedness of the technique for routine analysis of 4-OH Tam.
authors.affiliation: CEMAF Research Centre, Poitiers, France.
authors.forename: J
authors.initials: J
authors.lastname: Girault
authors.forename: B
authors.initials: B
authors.lastname: Istin
authors.forename: J B
authors.initials: JB
authors.lastname: Fourtillan
mesh_terms: D000970:Antineoplastic Agents / Q000032:analysis* / Q000097:blood / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000097:blood / Q000737:chemistry / Q000188:drug therapy*; D008401:Gas Chromatography-Mass Spectrometry / Q000379:methods*; D006801:Humans; D013629:Tamoxifen / Q000031:analogs & derivatives* / Q000032:analysis / Q000097:blood / Q000627:therapeutic use
chemical_list: D000970:Antineoplastic Agents; D013629:Tamoxifen; C016601:afimoxifene