Determination of paclitaxel in rat plasma by LC-MS-MS.

A simple, rapid, and sensitive liquid chromatography-mass spectrometry (MS)-MS method for quantitating paclitaxel in rat plasma is developed. Liquid-liquid extraction with tert-butyl methyl ether is used for sample preparation, and docetaxel is used as the internal standard. Paclitaxel and docetaxel are separated on a C18 column and quantitated using a triple-quadrupole MS operating in positive ion electrospray selective reaction monitoring mode with a total run time of 6.0 min. The peak area of the m/z 876.3 --> 307.9 transition of paclitaxel is measured versus that of the m/z 830.3 --> 549.1 transition of docetaxel to generate the standard curve. The standard curve is linear over the concentration range of 0.2008-1004 ng/mL for rat plasma. The method has high extraction recovery (> 90%) and accuracy (> 90%), with the intra- and interday precision < 15%. Frozen stability, freeze-and-thaw stability, extracted stability, and room temperature solution stability are also examined. This assay is used to support a pharmacokinetic study of paclitaxel self-assembled nanoliposome in rats.