LC-MS／MS测定大鼠全血纳米粒中伊立替康及其代谢物SN-38的浓度  

Determination of Irinotecanand Its Metabolite SN-38 in Nanoparticles by LC-MS /MS in Rats Whole Blood

作　　者：党宏万[1] 杨付英[2] 张文萍[1] 陈和莉[3] 王欣瑜[1] 冯小亮[4] 

机构地区：[1]宁夏医科大学总医院药剂科,宁夏750004 [2]宁夏医科大学总医院肿瘤医院药剂科,宁夏750004 [3]第三军医大学西南医院药学部,重庆400038 [4]宁夏医科大学附属回医中医医院,宁夏751100

出　　处：《中国药学杂志》2014年第5期396-400,共5页Chinese Pharmaceutical Journal

摘　　要：目的建立高效液相-质谱联用（LC-MS/MS）测定大鼠全血中伊立替康（CPT-II）及其代谢物7乙基10固定基喜树碱（SN 38 ）浓度的方法ρ方法采用液液法才是取大鼠全血中药物，以地西;半为内标;使用到lim- pack XR-ODS（2. 0 mm × 100 mm， 2.2 μm）色谱柱，以5 mmol · L-1甲酸接缓冲液（ A）-乙腊（B）为流动相，梯度流速恒定为： 0. 3 mL · min^- 1柱温为35 ℃，进样量10μt，总分析时间为4.2 min.质谱采用电喷雾离子源，以多反应离子监测模式进行定量分析结果 伊立替康及其代谢物工乙基10-在基喜树碱线性范围分别为1-2000和0.5 - 100 ng · mL - 1 ;全血中伊立替康及工乙基10发基喜树碱的LLOQ分别为l和0.5ng· mL^-1.伊立替康和7-乙基10-发基喜树碱质控样品的批内RSD小于9.439毛和11. 39% ，批间RSD小于9.73%和11. 79%，提取回收率分别在73.7% -117.4%和61. 7% -75.5%肉。结论 本方法灵敏度高，准确，干扰少，可应用于大鼠全血中伊立替康及其代谢物7-乙基10-究基喜树碱浓度的测定和药动学研究。OBJECTIVE To develop an LC-MS/MS method for detennination of irinotecanin nanoparticles and its metabolite SN- 38 in rats whole blood. METHODS The drugs were using liquid-liquid extraction method in rats of whole blood ,with diazepam as an internal standard. The Shim-pack XR-ODS （2.0 mm X 100mm, 2.2 μm ） column was used. The gradient mobile phase consisted of 5 mmol .· L-1ammonium formates solution （ A） and Acetonitrile （B） at the flow rate of 0.3 mL · min^- 1 , the injection volume was IOfLL and the column temperature was 35 ℃. The total time of the analysis was 4. 2 min. Electrospray ionization sourceand selective ion monitoringwere employed. RESULTS The linear ranges of irinotecan and SN-38 were 1 - 2 000 and O. 5 - 100 ng · mL - 1, respectively; lower limit of quantification（ LLOQ） was 1 and 0.5 ng· mL - 1 , respectively; the intra-batch RSO were less than 9. 43 ok） and II. 39% , respectively, the inter-batch RSD were less than 9.73% and 11. 79%, respectively. The extraction recoveries were 73.7% -117.4% and 61. 7% -75.5% , respectively. CONCLUSION The method had less interference and is sensitive, accurate for the determination of irinotecan and its metabolite SN-38 in the whole blood of rats.

关 键 词：伊立替康 SN-38 高效液相-质谱联用 液液萃取 

分 类 号：R969.1[医药卫生—药理学]