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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Kip, A. E. Rosing, H. Hillebrand, M. J. X. Castro, M. M. Gomez, M. A. Schellens, J. H. M. Beijnen, J. H. Dorlo, T. P. C. |
| Description | Author Affiliation: Kip AE ( Department of Pharmacy & Pharmacology, Antoni van Leeuwenhoek Hospital/Slotervaart Hospital, Amsterdam, The Netherlands); Rosing H ( Department of Pharmacy & Pharmacology, Antoni van Leeuwenhoek Hospital/Slotervaart Hospital, Amsterdam, The Netherlands.); Hillebrand MJ ( Department of Pharmacy & Pharmacology, Antoni van Leeuwenhoek Hospital/Slotervaart Hospital, Amsterdam, The Netherlands.); Castro MM ( Centro Internacional de Entrenamiento e Investigaciones Medicas (CIDEIM), Cali, Colombia.); Gomez MA ( Centro Internacional de Entrenamiento e Investigaciones Medicas (CIDEIM), Cali, Colombia.); Schellens JH ( Division of Pharmacoepidemiology & Clinical Pharmacology, Utrecht Institute for Pharmaceutical Sciences (UIPS), Faculty of Science, Utrecht University, Utrecht, The Netherlands); Beijnen JH ( Department of Pharmacy & Pharmacology, Antoni van Leeuwenhoek Hospital/Slotervaart Hospital, Amsterdam, The Netherlands); Dorlo TP ( Division of Pharmacoepidemiology & Clinical Pharmacology, Utrecht Institute for Pharmaceutical Sciences (UIPS), Faculty of Science, Utrecht University, Utrecht, The Netherlands.) |
| Abstract | Phagocytes, the physiological compartment in which Leishmania parasites reside, are the main site of action of the drug miltefosine, but the intracellular pharmacokinetics of miltefosine remain unexplored. We developed a bioanalytical method to quantify miltefosine in human peripheral blood mononuclear cells (PBMCs), expanding from an existing high performance liquid chromatography-tandem mass spectrometry method for the quantification of miltefosine in plasma. The method introduced deuterated miltefosine as an internal standard. Miltefosine was extracted from PBMC pellets by addition of 62.5% methanol. Supernatant was collected, evaporated and reconstituted in plasma. Chromatographic separation was performed on a reversed phase C18 column and detection with a triple-quadrupole mass spectrometer. Miltefosine was quantified using plasma calibration standards ranging from 4 to 1000ng/mL. This method was validated with respect to its PBMC matrix effect, selectivity, recovery and stability. No matrix effect could be observed from the PBMC content (ranging from 0.17 to 26.3×10(6)PBMCs) reconstituted in plasma, as quality control samples were within 3.0% of the nominal concentration (precision less than 7.7%). At the lower limit of quantitation of 4 ng/mL plasma, corresponding to 0.12ng/10(6) PBMCs in a typical clinical sample, measured concentrations were within 8.6% of the nominal value. Recovery showed to be reproducible as adding additional pre-treatment steps did not increase the recovery with more than 9%. This method was successfully applied to measure intracellular miltefosine concentrations in PBMC samples from six cutaneous leishmaniasis patients up to one month post-treatment. |
| File Format | HTM / HTML |
| ISSN | 15700232 |
| e-ISSN | 1873376X |
| DOI | 10.1016/j.jchromb.2015.06.017 |
| Journal | Journal of Chromatography B |
| Volume Number | 998-999 |
| Language | English |
| Publisher | Elsevier |
| Publisher Date | 2015-08-15 |
| Publisher Place | Netherlands |
| Access Restriction | Open |
| Subject Keyword | Discipline Analytical Chemistry Antiprotozoal Agents Chromatography, High Pressure Liquid Leukocytes, Mononuclear Chemistry Phosphorylcholine Analogs & Derivatives Tandem Mass Spectrometry Evaluation Studies Research Support, Non-u.s. Gov't |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cell Biology Medicine Analytical Chemistry Clinical Biochemistry Biochemistry |
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