Highly sensitive liquid chromatography-electrospray mass spectrometry (LC-MS) method for the determination of etoposide levels in human serum and plasma

摘要

Etoposide is one of the most commonly used antineoplastic agents. A highly sensitive liquid chromatographv—electrospravy mass spectrometry (LC—MS) method was developed fot the determination of etoposide in human serum and plasma. Etoposide was extracted with chloroform and extracts were reconstituted in acetonitrile followed by the evaporation ofchloroform with nitrogen gas. Etoposide was separated using Lichospher 100 RP- 18 (5 g.Lm) column (250 mmX4 mm) withthe mobile phase of acetonitrile—water containing 0.1% acetic acid (45/55, v/v) at flow-rate of 0.5 mI/mm. Selected-ion monitoging (SIM) mode was performed on m/z 589 (positive ion mode) using a fragmentor of 75 V Good linearity(r>0.9965) was observed between concentrations of 0.0125—5 ji.AI in 200 pA serum and 0.01—10 p.M in 100 #mu#l plasma. Intra- and inter-assay variabilities were less than 7% and the lowest detection limit of etoposide ~as 0.005 p.M in both serum and plasma at a signal-to-noise ratio of ~4. The etoposide concentrations in four cancer patients treated with etoposide are also presented to demonstrate the clinical utility of this new method, which should aid the pharmacokinetically guided use of etoposide in clinical settings.