A Sensitive and Efficient Method for Determination of Capecitabine and Its Five Metabolites in Human Plasma Based on One-Step Liquid-Liquid Extraction.

ABSTRACT: Colorectal cancer is the most common critical disease both in the developed and developing countries. Capecitabine, which has served in clinical practice at least for 10 years, is a first-line antidigestive tract cancer drug for its better efficacy, patient compliance, and lower side effects. An ultra-high-performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) method has been developed and completely validated for simultaneous determination of capecitabine and its five metabolites in human plasma from colorectal cancer patients after administration of capecitabine tablet. One-step liquid-liquid extraction was successfully applied using ethyl acetate and isopropanol (19?:?1, V?:?V) for sample pretreatment. Chromatographic separation was achieved within 5?min based on an Atlantis T3-C18 column (3.0?µm, 2.1?×?100?mm) with gradient elution using mobile phases consisting of 0.0075% formic acid in water (pH 4) and in acetonitrile, and the flow rate was 0.3?mL/min. Linear range was approximately 20.0-5000.0?ng/mL for all analytes. Linear correlation coefficients were >0.99 for all regression curves. The intraday and interday accuracy and precision of the method were within ±15.0% and less than 15.0%, respectively. The mean recovery and matrix effect as well as stability of all the analytes ranged from 59.27% to 90.15% and from 74.84% to 114.48% as well as within ±15.0%. This simple, rapid, and sensitive method was successfully applied in 42 sparse clinical samples to verify its practicability.

SUBMITTER: Wang Z 

PROVIDER: S-EPMC6335671 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature