Pharmacokinetics of paclitaxel nanoliposome in rats by LC-MS/MS

OBJECTIVE To study the pharmacokinetics of paclitaxel nanoliposome in rats administered i.v.METHODS A LC-MS/MS method based on positive electrospray ionization(ESI~(+)-MS-MS) for quantifying paclitaxel in rat blood has been developed.Liquid-liquid extraction with tert-butyl methyl ether was used for plasma sample preparation and docetaxel was used as the internal standard.Paclitaxel nanoliposome and taxol injection were administered through tail vein.RESULTS The standard curve was linear over the concentration range of(0.2)-1 000 μg·L~(-1)(r=(0.999 6)).The method had a high extraction recovery(90%) and method recovery(90%) with intraday and interday precision of 15%.The plasma concentration-time profile in rat after iv injection of paclitaxel nanoliposome or taxol injection followed a bi-exponential disposition.t_(1/2)α were((0.71)±(0.25)) h and((0.438)±(0.023)) h,t_(1/2)β were((13.2)±(1.2)) h and((7.8)±(1.4)) h,AUC were((4 519.7)±(791.3)) μg·L~(-1)·h and((2 679.2)±(530.7)) μg·L~(-1)·h,respectively.CONCLUSION The LC-MS/MS method bears characteristics of high sensitivity,accuracy and reliability.Paclitaxel nanoliposme has a long-circulating action and improves bioavailabilty of paclitaxle in rat to some extent by comparison with conventional taxol injection.