title: Atomic absorption spectrometric determination of the iridium content in tumor cells exposed to an iridium metallodrug.
abstract: An electrothermal atomic absorption spectrometric method to quantify the iridium content of HT-29 colon carcinoma cells exposed to iridium metallodrugs was developed. Optimisation of the procedure involved the evaluation of pyrolysis and atomisation conditions (optimal values were 1400 degrees C for pyrolysis and 2400 degrees C for atomisation) and the addition of appropriate additives. The presence of cellular components as well as the addition of nitric acid and hydrochloric acid led to enhanced absorption signals and suggested the use of matrix matched calibration. The described method allows the measurement of iridium in cell suspensions in the low microg/L range (linear dynamic range: 10-450 microg/L) with a detection limit of 11.2 microg/L. The applicability of the method was tested by means of a novel iridium metallodrug. First results on the complex [IrCl3(DMSO)(phen)] indicated a low cellular uptake (21.2 microM at incubation with 100 microM) of this iridium species in HT-29 cells compared to other metal containing antitumor drugs.
authors.affiliation: Institute of Pharmacy, Freie Universität Berlin, Königin-Luise Str. 2+4, 14195 Berlin, Germany. ottingo@zedat.fu-berlin.de
authors.forename: Ingo
authors.initials: I
authors.lastname: Ott
authors.forename: Michael
authors.initials: M
authors.lastname: Scharwitz
authors.forename: Heike
authors.initials: H
authors.lastname: Scheffler
authors.forename: William S
authors.initials: WS
authors.lastname: Sheldrick
authors.forename: Ronald
authors.initials: R
authors.lastname: Gust
mesh_terms: D000970:Antineoplastic Agents / Q000032:analysis* / Q000493:pharmacokinetics / Q000627:therapeutic use; D002021:Buffers; D002138:Calibration; D018929:Cell Culture Techniques; D004121:Dimethyl Sulfoxide / Q000737:chemistry; D019073:HT29 Cells; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007495:Iridium / Q000032:analysis* / Q000592:standards; D010710:Phosphates / Q000737:chemistry; D012015:Reference Standards; D012997:Solvents / Q000737:chemistry; D013054:Spectrophotometry, Atomic / Q000379:methods*; D013696:Temperature
chemical_list: D000970:Antineoplastic Agents; D002021:Buffers; D010710:Phosphates; D012997:Solvents; D007495:Iridium; D004121:Dimethyl Sulfoxide