Quantitation of paclitaxel, and its 6-alpha-OH and 3-para-OH metabolites in human plasma by LC-MS/MS.

ABSTRACT: We have developed a high performance liquid chromatography mass spectrometry method for quantitating paclitaxel and its 6-alpha-OH and 3-para-OH metabolites in 0.1?mL human plasma. After MTBE liquid-liquid extraction, chromatographic separation was achieved with a Phenomenex synergy polar reverse phase (4??m, 2?mm?×?50?mm) column and a gradient of 0.1% formic acid in acetonitrile and water over an 8?min run time. Mass spectrometric detection was performed on an ABI SCIEX 4000Q with electrospray, positive-mode ionization. The assay was linear from 10-10,000?ng/mL for paclitaxel and 1-1000?ng/mL for both metabolites and proved to be accurate (94.3-110.4%) and precise (<11.3%CV). Recovery from plasma was 59.3-91.3% and matrix effect was negligible (-3.5 to 6.2%). Plasma freeze thaw stability (90.2-107.0%), stability for 37 months at -80?°C (89.4-112.6%), and stability for 4?h at room temperature (87.7-100.0%) were all acceptable. This assay will be an essential tool to further define the metabolism and pharmacology of paclitaxel and metabolites in the clinical setting. The assay may be utilized for therapeutic drug monitoring of paclitaxel and may also reveal the CYP2C8 and CYP3A4 activity phenotype of patients.

SUBMITTER: Christner SM 

PROVIDER: S-EPMC6548629 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature