کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
7616014 | 1494028 | 2016 | 6 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Liquid chromatography-mass spectrometry for measuring deoxythioguanosine in DNA from thiopurine-treated patients
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کلمات کلیدی
NBCSAZAIMPDH6-MercaptopurineTPMTTGNRBCIBDDTGITPaseHGPRTGMPsDNA - DNA یا اسید دزوکسی ریبونوکلئیکLC–MS/MS - LC-MS / MSazathioprine - آزاتیوپرین Crohn’s disease - بیماری کرونInflammatory bowel disease - بیماریهای التهابی رودهTIMP - زمانTandem mass spectrometry - طیف سنجی جرمی پشت سر هم یا متوالیDrug monitoring - نظارت بر مواد مخدرALL - همهhypoxanthine-guanine phosphoribosyl transferase - هیپوکسانتین-گوانین فسفریبوسیل ترانسفرازquality control - کنترل کیفیتUlcerative colitis - کولیت اولسراتیوred blood cell - گلبول قرمز، اریتروسیت
موضوعات مرتبط
مهندسی و علوم پایه
شیمی
شیمی آنالیزی یا شیمی تجزیه
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Adverse reactions and non-response are common in patients treated with thiopurine drugs. Current monitoring of drug metabolite levels for guiding treatment are limited to analysis of thioguanine nucleotides (TGNs) in erythrocytes after chemical derivatisation. Erythrocytes are not the target tissue and TGN levels show poor correlations with clinical response. We have developed a sensitive assay to quantify deoxythioguanosine (dTG) without derivatisation in the DNA of nucleated blood cells. Using liquid chromatography and detection by tandem mass spectrometry, an intra- and inter-assay variability below 7.8% and 17.0% respectively were achieved. The assay had a detection limit of 0.0003125Â ng (1.1 femtomoles) dTG and was quantified in DNA samples relative to endogenous deoxyadenosine (dA) in a small group of 20 patients with inflammatory bowel disease, all of whom had been established on azathioprine (AZA) therapy for more than 25 weeks. These patients had dTG levels of 20-1360Â mol dTG/106Â mol dA; three patients who had not started therapy had no detectable dTG. This method, comparable to previous methods in sensitivity, enables the direct detection of a cytotoxic thiopurine metabolite without derivatisation in an easily obtainable, stable sample and will facilitate a better understanding of the mechanisms of action of these inexpensive yet effective drugs.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Chromatography B - Volume 1028, 15 August 2016, Pages 175-180
Journal: Journal of Chromatography B - Volume 1028, 15 August 2016, Pages 175-180
نویسندگان
Sally A. Coulthard, Phil Berry, Sarah McGarrity, Azhar Ansari, Christopher P.F. Redfern,