A novel method for quantification of gemcitabine and its metabolites 2',2'-difluorodeoxyuridine and gemcitabine triphosphate in tumour tissue by LC-MS/MS: comparison with (19)F NMR spectroscopy.
A novel method for quantification of gemcitabine and its metabolites 2',2'-difluorodeoxyuridine and gemcitabine triphosphate in tumour tissue by LC-MS/MS: comparison with (19)F NMR spectroscopy.
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一种通过 LC-MS/MS 定量肿瘤组织中吉西他滨及其代谢物 2',2'-二氟脱氧尿苷和吉西他滨三磷酸的新方法：与 (19)F NMR 波谱比较。
DOI：
10.1007/s00280-011-1613-0
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发表时间：
2011-11
影响因子：
3
通讯作者：
Jodrell, Duncan I.
中科院分区：
文献类型：
--
作者：
Bapiro, Tashinga E.;Richards, Frances M.;Goldgraben, Mae A.;Olive, Kenneth P.;Madhu, Basetti;Frese, Kristopher K.;Cook, Natalie;Jacobetz, Michael A.;Smith, Donna-Michelle;Tuveson, David A.;Griffiths, John R.;Jodrell, Duncan I.
To develop a sensitive analytical method to quantify gemcitabine (2′,2′-difluorodeoxycytidine, dFdC) and its metabolites 2′,2′-difluorodeoxyuridine (dFdU) and 2′,2′-difluorodeoxycytidine-5′-triphosphate (dFdCTP) simultaneously from tumour tissue. Pancreatic ductal adenocarcinoma tumour tissue from genetically engineered mouse models of pancreatic cancer (KP FL/FL C and KP R172H/+ C) was collected after dosing the mice with gemcitabine. 19F NMR spectroscopy and LC–MS/MS protocols were optimised to detect gemcitabine and its metabolites in homogenates of the tumour tissue. A 19F NMR protocol was developed, which was capable of distinguishing the three analytes in tumour homogenates. However, it required at least 100 mg of the tissue in question and a long acquisition time per sample, making it impractical for use in large PK/PD studies or clinical trials. The LC–MS/MS protocol was developed using porous graphitic carbon to separate the analytes, enabling simultaneous detection of all three analytes from as little as 10 mg of tissue, with a sensitivity for dFdCTP of 0.2 ng/mg tissue. Multiple pieces of tissue from single tumours were analysed, showing little intra-tumour variation in the concentrations of dFdC or dFdU (both intra- and extra-cellular). Intra-tumoural variation was observed in the concentration of dFdCTP, an intra-cellular metabolite, which may reflect regions of different cellularity within a tumour. We have developed a sensitive LC–MS/MS method capable of quantifying gemcitabine, dFdU and dFdCTP in pancreatic tumour tissue. The requirement for only 10 mg of tissue enables this protocol to be used to analyse multiple areas from a single tumour and to spare tissue for additional pharmacodynamic assays.
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影响因子：
2.9
作者：
EDZES, HT;PETERS, GJ;VERMORKEN, JB
通讯作者：
VERMORKEN, JB
影响因子：
45.3
作者：
Eisbruch, A;Shewach, DS;Lawrence, TS
通讯作者：
Lawrence, TS
影响因子：
50.3
作者：
Hingorani, SR;Wang, LF;Tuveson, DA
通讯作者：
Tuveson, DA
影响因子：
1.8
作者：
Peters, G. J.;Clavel, M.;Vermorken, J. B.
通讯作者：
Vermorken, J. B.
DOI：
10.1126/science.1171362
发表时间：
2009-06-12
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Olive KP;Jacobetz MA;Davidson CJ;Gopinathan A;McIntyre D;Honess D;Madhu B;Goldgraben MA;Caldwell ME;Allard D;Frese KK;Denicola G;Feig C;Combs C;Winter SP;Ireland-Zecchini H;Reichelt S;Howat WJ;Chang A;Dhara M;Wang L;Rückert F;Grützmann R;Pilarsky C;Izeradjene K;Hingorani SR;Huang P;Davies SE;Plunkett W;Egorin M;Hruban RH;Whitebread N;McGovern K;Adams J;Iacobuzio-Donahue C;Griffiths J;Tuveson DA
通讯作者：
Tuveson DA