Li Dan, Zhao Gang, Ai Weipeng, Li Gao, Si Luqin, Huang Jiangeng, Chen Yunzhou, Wu Sanlan
Department of Pharmacy, Shenzhen University Genneral Hospital, Shenzhen, Guangdong, People' Republic of China.
Department of Pharmaceutics, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People' Republic of China.
Biomed Chromatogr. 2018 Jun;32(6):e4192. doi: 10.1002/bmc.4192. Epub 2018 Feb 22.
In this study, a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated to simultaneously determine the anticancer drugs etoposide and paclitaxel in mouse plasma and tissues including liver, kidney, lung, heart, spleen and brain. The analytes were extracted from the matrices of interest by liquid-liquid extraction using methyl tert-butyl ether-dichloromethane (1:1, v/v). Chromatographic separation was achieved on an Ultimate XB-C column (100 × 2.1 mm, 3 μm) at 40°C and the total run time was 4 min under a gradient elution. Ionization was conducted using electrospray ionization in the positive mode. Stable isotope etoposide-d3 and docetaxel were used as the internal standards. The lower limit of quantitation (LLOQ) of etoposide was 1 ng/g tissue for all tissues and 0.5 ng/mL for plasma. The LLOQ of paclitaxel was 0.4 ng/g tissue and 0.2 ng/mL for all tissues and plasma, respectively. The coefficients of correlation for all of the analytes in the tissues and plasma were >0.99. Both intra- and inter-day accuracy and precision were satisfactory. This method was successfully applied to measure plasma and tissue drug concentrations in mice treated with etoposide and paclitaxel-loaded self-microemulsifying drug-delivery systems.
在本研究中，开发并验证了一种液相色谱 - 串联质谱（LC-MS/MS）方法，用于同时测定小鼠血浆以及肝脏、肾脏、肺、心脏、脾脏和大脑等组织中的抗癌药物依托泊苷和紫杉醇。通过使用甲基叔丁基醚 - 二氯甲烷（1:1，v/v）进行液 - 液萃取，从感兴趣的基质中提取分析物。在Ultimate XB-C柱（100×2.1 mm，3 μm）上于40°C进行色谱分离，在梯度洗脱条件下总运行时间为4分钟。采用正模式电喷雾电离进行离子化。使用稳定同位素依托泊苷 - d3和多西他赛作为内标。依托泊苷在所有组织中的定量下限（LLOQ）为1 ng/g组织，在血浆中为0.5 ng/mL。紫杉醇在所有组织和血浆中的LLOQ分别为0.4 ng/g组织和0.2 ng/mL。组织和血浆中所有分析物的相关系数均>0.99。日内和日间的准确度和精密度均令人满意。该方法成功应用于测定用负载依托泊苷和紫杉醇的自微乳化药物递送系统处理的小鼠的血浆和组织药物浓度。
