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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Mueller, Daniel M. Rentsch, Katharina M. |
| Description | Country affiliation: Switzerland Author Affiliation: Mueller DM ( Institute for Clinical Chemistry, University Hospital Zurich, Raemistrasse 100, 8091 Zuerich, Switzerland.) |
| Abstract | Sirolimus and its derivative everolimus are widely used today as immunosuppressive agents for example in the transplantation medicine. The problematic pharmacokinetic behavior of those substances makes therapeutic drug monitoring mandatory. Therefore, a fast, simple and sensitive high-throughput procedure using online extraction with turbulent flow chromatography for the concurrent measurement of sirolimus and everolimus has been developed. 200 microl of whole blood was mixed with internal standard (23-desmethoxyrapamycin) and the precipitation solution and centrifuged. An aliquot of the supernatant was transferred into autosampler vials. 50 microl of the supernatant was injected into the LC system, where the analytes were extracted using turbulent flow chromatography and thereafter analyzed using reversed phase chromatography. Detection was done by atmospherical pressure chemical ionization (APCI) mass spectrometry in the negative ionization mode. The method has been fully validated and compared to a previously used method. The method was shown to be linear over the entire calibration range (2.2-43.7 microg/l for everolimus and 2.9-51.2 microg/l for sirolimus). The lower limit of quantification was 0.5 microg/l for both compounds. For within-day and between-day analysis, the CV's were <7.6% for everolimus and <8.7% for sirolimus, respectively. The accuracy was between 92.1% and 105% for everolimus and 96.1% and 106% for sirolimus. Recovery ranged between 46.3% and 50.6% for everolimus and 51.2% and 57.2% for sirolimus. The method was demonstrated to be free of matrix effects and comparable to the previously used method. The presented LC-MS/MS method, using turbulent flow chromatography online extraction, allows a fast, simple and reliable determination of everolimus and sirolimus. |
| File Format | HTM / HTML |
| ISSN | 15700232 |
| Issue Number | 13-14 |
| Volume Number | 878 |
| e-ISSN | 1873376X |
| Journal | Journal of Chromatography B |
| Language | English |
| Publisher | Elsevier |
| Publisher Date | 2010-04-15 |
| Publisher Place | Netherlands |
| Access Restriction | One Nation One Subscription (ONOS) |
| Subject Keyword | Discipline Analytical Chemistry Chromatography, Liquid Methods Immunosuppressive Agents Pharmacokinetics Sirolimus Analogs & Derivatives Blood Tandem Mass Spectrometry Everolimus Humans Reference Standards Reproducibility Of Results Journal Article |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cell Biology Medicine Analytical Chemistry Clinical Biochemistry Biochemistry |
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