title: Determination of a novel epothilone D analog (AV-EPO-106) in human plasma using ultra-performance liquid chromatography-tandem mass spectrometry.
abstract: 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 C(18) 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 microg/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 microg/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 microg/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.
authors.affiliation: Department of Pharmaceutics, The University of Mississippi, MS 38677, USA.
authors.forename: Shuang-Qing
authors.initials: SQ
authors.lastname: Zhang
authors.forename: Harsha
authors.initials: H
authors.lastname: Vinnakota
authors.forename: Jae-Chul
authors.initials: JC
authors.lastname: Jung
authors.forename: Paulo
authors.initials: P
authors.lastname: Carvalho
authors.forename: Amar G
authors.initials: AG
authors.lastname: Chittiboyina
authors.forename: Mitchell A
authors.initials: MA
authors.lastname: Avery
authors.forename: Bonnie A
authors.initials: BA
authors.lastname: Avery
mesh_terms: D002851:Chromatography, High Pressure Liquid; D004355:Drug Stability; D034261:Epothilones / Q000097:blood*; D006207:Half-Life; D006801:Humans; D016014:Linear Models; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D053719:Tandem Mass Spectrometry; D050257:Tubulin Modulators / Q000097:blood*
chemical_list: C542723:AV-EPO-106; D034261:Epothilones; D050257:Tubulin Modulators; C114026:desoxyepothilone B