Determination of a novel epothilone D analog (AV-EPO-106) in human plasma using ultra-performance liquid chromatography–tandem mass spectrometry
Article first published online: 17 SEP 2008
Copyright © 2008 John Wiley & Sons, Ltd.
Volume 23, Issue 3, pages 302–307, March 2009
How to Cite
Zhang, S.-Q., Vinnakota, H., Jung, J.-C., Carvalho, P., Chittiboyina, A. G., Avery, M. A. and Avery, B. A. (2009), Determination of a novel epothilone D analog (AV-EPO-106) in human plasma using ultra-performance liquid chromatography–tandem mass spectrometry. Biomed. Chromatogr., 23: 302–307. doi: 10.1002/bmc.1114
- Issue published online: 9 FEB 2009
- Article first published online: 17 SEP 2008
- Manuscript Accepted: 24 JUN 2008
- Manuscript Revised: 23 JUN 2008
- Manuscript Received: 24 APR 2008
- epothilone D analog;
- ultra-performance liquid chromatography–tandem mass spectrometry;
- human plasma
A novel ultra-performance liquid chromatography–tandem mass spectrometry (UPLC-MS-MS) method has been established for the determination of a newly synthesized epothilone D analog (AV-EPO-106) in human plasma. The plasma samples were prepared by liquid–liquid extraction with cold tert-butyl methyl ether. The chromatographic separation was achieved within 5 min on a C18 column with water–methanol (10:90, v/v) as mobile phase at a flow-rate of 0.8 mL/min. Mass transition of m/z 568.2 to 386.1 was measured for AV-EPO-106 in positive atmospheric pressure chemical ionization mode. A detailed validation of the method was performed as per the USFDA guidelines. For AV-EPO-106 at the concentrations of 1.0, 5.0 and 10.0 µg/mL in human plasma, the absolute extraction recoveries were 86.17, 85.24 and 85.69%, respectively. The linear quantification range of the method was 0.10–20.0 µg/mL in human plasma with linear correlation coefficients greater than 0.999. The intra-day and inter-day accuracy for AV-EPO-106 at the levels of 1.0, 5.0 and 10.0 µg/mL in human plasma fell in the ranges of 98.25–100.47 and 94.19–97.25%, and the intra- and inter-day precision were in the ranges of 4.75–6.30% and 8.89–10.45%, respectively. The method was successfully applied to quantify AV-EPO-106 in human plasma to determine the half-life of this compound in human plasma. Copyright © 2008 John Wiley & Sons, Ltd.