One-Step Solid Extraction for Simultaneous Determination of Eleven Commonly Used Anticancer Drugs and One Active Metabolite in Human Plasma by HPLC-MS/MS

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 T(3)-C(18) 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.