Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
10161969 | Journal of Pharmaceutical Sciences | 2015 | 6 Pages |
Abstract
Gemcitabine (2â²,2â²-difluoro-2â²-deoxycytidine, dFdC) and metabolite (2â²,2â²-difluoro-2â²-deoxyuridine, dFdU) quantification is warranted for individualized treatment strategies. Analyte stability is crucial for the validity of such quantification. We therefore studied the impact of the time interval from blood sampling to separation of plasma on gemcitabine stability. Blood from gemcitabine-treated patients was drawn into tetrahydrouridine (THU)-spiked heparin and ethylenediaminetetraacetic acid tubes and kept on ice until separation. Plasma was separated sequentially up to 24Â h after sampling and dFdC and dFdU were quantified by liquid chromatography tandem mass spectrometry (LC-MS/MS). The change in plasma concentrations over time was compared with the highest imprecision for concentrations above the lower limit of quantification of the LC-MS/MS method. Analyte concentrations decreased slightly over time, but for samples stored for 4Â h on ice, the decline was smaller than the expected analytical imprecision. After 24Â h, the maximum decline was 14.0%, which exceeded the expected analytical imprecision. dFdC and dFdU stabilities were acceptable for at least 4Â h when THU-spiked whole blood samples were kept on ice. This is within the scope of routine sampling procedures. Further, variations in separation time intervals within this time frame are negligible when interpreting drug concentrations.
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Authors
Tormod BjÃ¥nes, Tina KamÄeva, Torunn Eide, Bettina Riedel, Jan Schjøtt, Asbjørn Svardal,