Quantitative method for the determination of iso-fludelone (KOS-1803) in human plasma by LC-MS/MS Journal Article
| Authors: | Christner, S. M.; Parise, R. A.; Levine, E. D.; Rizvi, N. A.; Gounder, M. M.; Beumer, J. H. |
| Article Title: | Quantitative method for the determination of iso-fludelone (KOS-1803) in human plasma by LC-MS/MS |
| Abstract: | Epothilones are relatively new tubulin-poison anticancer drugs. Iso-fludelone (KOS-1803) is a synthetic third generation epothilone drug discovered at Memorial Sloan Kettering Cancer Center, and currently in phase I clinical trials. We report an LC-MS/MS assay for the sensitive, accurate and precise quantitation of iso-fludelone in 0.2. mL of human plasma. Validation was performed according to FDA guidance. The assay comprised of KOS-1724 as the internal standard and an MTBE liquid-liquid extraction with a water wash step. Separation was achieved with an YMC-Pack ODS-AQ column and an isocratic mobile phase of 0.1% formic acid in acetonitrile and water (70:30, v/v) at 0.3. mL/min for 4. min. Chromatographic separation was followed by electrospray, positive-mode ionization tandem mass spectrometric detection in the multiple reaction monitoring (MRM) mode. The assay was linear from 0.1 to 300. ng/mL and was accurate (-9.41 to -7.07%) and precise (1.03-13.7%) which fulfilled FDA criteria for validation. Recovery from plasma was 73.9-79.7% and ion suppression was negligible (-22.8 to -31.3%). Plasma freeze-thaw stability (99.97-105.7%), stability for 11 months at -80. °C (94.93-107.9%), and stability for 6. h at room temperature (94.75-105.5%) were all acceptable. This assay is currently being applied to quantitate iso-fludelone in clinical samples. © 2014 Elsevier B.V. |
| Keywords: | controlled study; unclassified drug; signal noise ratio; assay; standard; quantitative analysis; tandem mass spectrometry; water; liquid chromatography; drug determination; freeze thawing; validation; plasma; drug stability; room temperature; electric potential; lc-ms/ms; ixabepilone; epothilone derivative; epothilone; anticoagulant agent; phase 1 clinical trial (topic); electrospray mass spectrometry; ionization; acetonitrile; limit of quantitation; measurement accuracy; human; priority journal; article; gas flow; kos-1803 (iso-fludelone); formic acid; iso fludelone; kos 1803; liquid liquid extraction |
| Journal Title: | Journal of Pharmaceutical and Biomedical Analysis |
| Volume: | 100 |
| ISSN: | 0731-7085 |
| Publisher: | Elsevier Science BV |
| Date Published: | 2014-11-01 |
| Start Page: | 199 |
| End Page: | 204 |
| Language: | English |
| DOI: | 10.1016/j.jpba.2014.08.007 |
| PROVIDER: | scopus |
| PMCID: | PMC4179924 |
| PUBMED: | 25168219 |
| DOI/URL: | |
| Notes: | Export Date: 1 October 2014 -- Source: Scopus |
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