Determination of a novel paclitaxel derivative (NPD-103) in human plasma by ultra-performance liquid chromatography-tandem mass spectrometry.

A sensitive and specific ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS-MS) method for quantification of a newly developed anticancer agent NPD-103 has been established. An aliquot of human plasma sample (200 microL) was spiked with (13)C-labeled paclitaxel (internal standard) and extracted with 1.3 mL of tert-butyl methyl ether. NPD-103 was quantitated on a C(18) column with methanol-0.1% formic acid (75:25, v/v) as mobile phase using UPLC-MS-MS operating in positive electrospray ionization mode with a total run time of 3.0 min. For NPD-103 at the concentrations of 1.0, 5.0 and 10.0 microg/mL in human plasma, the absolute extraction recoveries were 95.58, 102.43 and 97.77%, respectively. The linear quantification range of the method was 0.1-20.0 microg/mL in human plasma with linear correlation coefficients greater than 0.999. The intra- and inter-day accuracy for NPD-103 at 1.0, 5.0 and 10.0 microg/mL levels in human plasma fell into the ranges of 95.29-100.00% and 91.04-94.21%, and the intra- and inter-day precisions were in the ranges of 8.96-11.79% and 7.25-10.63%, respectively. This assay is applied to determination of half-life of NPD-103 in human plasma.