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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Jansen, Robert S. Rosing, Hilde Kromdijk, Wiete Ter Heine, Rob Schellens, Jan Hm Beijnen, Jos H. |
| Description | Country affiliation: Netherlands Author Affiliation: Jansen RS ( Department of Pharmacy & Pharmacology, Slotervaart Hospital/The Netherlands Cancer Institute, Louwesweg 6, 1066 EC Amsterdam, The Netherlands. Robert.jansen@slz.nl) |
| Abstract | Emtricitabine (FTC) and tenofovir (TFV) are widely used antiviral agents that require intracellular phosphorylation to become active. This article describes the development and validation of an assay for the simultaneous quantification of FTC mono-, di- and triphosphate (FTC-MP, -DP and -TP), TFV and TFV mono- and diphosphate (TFV-MP and -DP) in peripheral blood mononuclear cells. Reference compounds and internal standards were obtained by thermal degradation of FTC-TP, TFV-DP, stable isotope-labeled TFV-DP and stable isotope-labeled cytosine triphosphate. Cells were lysed in methanol:water (70:30, v/v) and the extracted nucleotides were analyzed using weak anion-exchange chromatography coupled with tandem mass spectrometry. Calibration ranges in PBMC lysate from 0.727 to 36.4, 1.33 to 66.4 and 1.29 to 64.6 nM for FTC-MP, FTC-DP and FTC-TP and from 1.51 to 75.6, 1.54 to 77.2 and 2.54 to 127 nM for TFV, TFV-MP and TFV-DP, respectively, were validated. Accuracies were within -10.3 and 16.7% deviation at the lower limit of quantification at which the coefficients of variation were less than 18.2%. At the other tested levels accuracies were within -14.3 and 9.81% deviation and the coefficients of variation lower than 14.7%. The stability of the compounds was assessed under various analytically relevant conditions. The method was successfully applied to clinical samples. |
| File Format | HTM / HTML |
| ISSN | 15700232 |
| Issue Number | 7-8 |
| Volume Number | 878 |
| e-ISSN | 1873376X |
| Journal | Journal of Chromatography B |
| Language | English |
| Publisher | Elsevier |
| Publisher Date | 2010-03-01 |
| Publisher Place | Netherlands |
| Access Restriction | One Nation One Subscription (ONOS) |
| Subject Keyword | Discipline Analytical Chemistry Adenine Analogs & Derivatives Chromatography, Ion Exchange Methods Deoxycytidine Leukocytes, Mononuclear Chemistry Nucleotides Blood Organophosphonates Tandem Mass Spectrometry Adenine Nucleotides Anions Drug Stability Emtricitabine Humans Linear Models Phosphorylation Pyrimidine Nucleotides Reproducibility Of Results Tenofovir Journal Article |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cell Biology Medicine Analytical Chemistry Clinical Biochemistry Biochemistry |
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