Simultaneous Quantification of Paclitaxel Prodrug and its Released Paclitaxel in Human Plasma by UPLC-MS/MS

Shuang-Qing      Zhang; Yu-Ming      Fan

Abstract

A specific ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was established and validated for the simultaneous quantification of paclitaxel prodrug (PP) and paclitaxel (PT) in human plasma. PP, PT and an internal standard 13C6-labelled PT (13C6-PT) were extracted from plasma by tert-butyl methyl ether and separated on an ACQUITY UPLC BEH C18 column (50 mm × 2.1 mm, 1.7 μm) using a mobile phase of methanolacetonitrile 50:50 (v/v) at a flow rate of 0.4 mL/min. At positive electrospray ionization mode, multiple reaction monitoring of the precursor-product ion transitions of m/z 882.2→313.9 for 13C6-PT, 876.2→307.9 for PT and 1216.5→647.8 for PP was used for the quantification. The linear calibration curve was obtained in a concentration range of 1-1000 ng/mL with a lower limit of quantification of 1 ng/mL. For both analytes, the values of intra- and inter-day precision were within 12.5% and accuracy fell in the ranges of 91.5-103.4%. The recovery ranged from 88.1% to 94.2% and the matrix effects from 89.3% to 95.4%. PP and PT were stable under short-term temperature and post-preparative conditions. The method was applied to stability of PP in human plasma and released PT from PP.

Keywords: Paclitaxel prodrug, paclitaxel, ultra-performance liquid chromatography-tandem mass spectrometry, stability in plasma

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