Wang Zhipeng, Li Xinxing, Yang Yang, Zhang Feng, Li Mingming, Chen Wei, Gao Shouhong, Chen Wansheng
Department of Pharmacy, Changzheng Hospital, Second Military Medical University, Shanghai 200003, China.
Department of General Surgery, Changzheng Hospital, Second Military Medical University, Shanghai 200003, China.
J Anal Methods Chem. 2019 Jan 3;2019:9371790. doi: 10.1155/2019/9371790. eCollection 2019.
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-C column (3.0 m, 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.
结直肠癌是发达国家和发展中国家最常见的重大疾病。卡培他滨已在临床实践中应用至少10年，因其疗效更好、患者依从性高且副作用较低，是治疗消化道癌症的一线药物。已开发并完全验证了一种超高效液相色谱串联质谱法（UHPLC-MS/MS），用于同时测定卡培他滨片给药后结直肠癌患者血浆中卡培他滨及其五种代谢物。采用乙酸乙酯和异丙醇（19∶1，V∶V）成功进行一步液液萃取用于样品预处理。基于Atlantis T3-C柱（3.0μm，2.1×100mm），使用由0.0075%甲酸水溶液（pH 4）和乙腈组成的流动相进行梯度洗脱，在5分钟内实现色谱分离，流速为0.3mL/min。所有分析物的线性范围约为20.0 - 5000.0ng/mL。所有回归曲线的线性相关系数均>0.99。该方法的日内和日间准确度和精密度分别在±15.0%以内和小于15.0%。所有分析物的平均回收率、基质效应以及稳定性范围分别为59.27%至90.15%、74.84%至114.48%以及在±15.0%以内。这种简单、快速且灵敏的方法成功应用于42份稀疏临床样本以验证其实用性。
