One-step solid extraction for simultaneous determination of eleven commonly used anticancer drugs and one active metabolite in human plasma by HPLC-MS/MS

Abstract

Therapeutic drug monitoring for anticancer drugs could timely reflect in vivo drug exposure, and it was a powerful tool for adjusting and maintaining drug concentration into a reasonable range, so that an enhanced efficacy and declined adverse reactions could be achieved. A liquid chromatography-tandem mass spectrometry method had been developed and fully validated for simultaneous determination of paclitaxel, docetaxel, vinblastine, vinorelbine, pemetrexed, carboplatin, etoposide, cyclophosphamide, ifosfamide, gemcitabine, irinotecan, and SN-38 (an active metabolite of irinotecan) in human plasma from cancer patients after intravenous drip of chemotherapy drugs. One-step solid-phase extraction was successfully applied using an Ostro sample preparation 96-well plate for plasma samples pretreated with acetonitrile containing 0.1% formic acid. Chromatographic separation was achieved on an Atlantis T3-C18 column (2.1 × 100 mm, 3.0 μm) with gradient elution using a mobile phase consisting of acetonitrile and 10 mM ammonium acetate plus 0.1% formic acid in water, and the flow rate was 0.25 mL/min. The Agilent G6410A triple quadrupole liquid chromatography-mass spectrometry system was operated under the multiple reaction monitoring mode with an electrospray ionization in the positive mode. Linear range was 25.0-2500.0 ng for paclitaxel, 10.0-1000.0 ng for docetaxel and SN-38, 100.0-10000.0 ng for vinorelbine and pemetrexed, 10.0-10000.0 ng for vinblastine and irinotecan, 1.0-1000.0 ng for cyclophosphamide and ifosfamide, 50.0-5000.0 ng for carboplatin, etoposide, and gemcitabine. Linearity coefficients of correlation were >0.99 for all analytes. The intraday and interday accuracy and precision of the method were within ±15.0% and less than 15%. The mean recovery and matrix effect as well as stability of all the analytes ranged from 56.2% to 98.9% and 85.2% to 101.3% as well as within ±15.0%. This robust and efficient method was successfully applied to implement therapeutic drug monitoring for cancer patients in clinical application.