脑肿瘤间质化疗BCNU缓释微球的载药量高效液相色谱测定  

HPLC detection of BCNU loading of controlled-release microspheres in interstitial chemotherapy of cerebral tumors

作　　者：马晓东[1] 章文斌[1] 李芹[2] 周定标[1] 许百男[1] 

机构地区：[1]解放军总医院神经外科,北京100853 [2]中国海洋大学海洋药物与食品研究所,山东青岛266003

出　　处：《中华神经外科疾病研究杂志》2006年第6期522-525,共4页Chinese Journal of Neurosurgical Disease Research

摘　　要：目的建立体外磷酸盐缓冲溶液（PBS）聚乳酸／羟基乙酸（PLGA）缓释卡氮芥（BCNU）微球药物浓度的高效液相色谱分析方法，并用此法研究缓释微球的体外释放动力学特征。方法采用依利特Hypersil ODS2 C18色谱柱（5μm，4．6mm×150mm），以甲醇：水（50：50）为流动相，流速1．0ml／min，紫外光检测波长237nm。结果BCNU在0．005—0．35μmol／ml范围内呈线性（r=0．9992），最低检测下限为0．005μmol／ml。采用低、中、高浓度（0．03、0．1、0．3μmol／m1）的方法回收率分别为103．33％、101．43％和102．04％，日间及日内相对标准偏差（RSD）分别〈4％和〈1％。体外药物释放动力学研究表明，PLGA缓释BCNU时间可达3w以上。结论本法准确可靠，操作简便，适用于缓释BCNU微球的体外药物释放动力学研究。Objective To establish a method for the detection of carmustine （1,3-bis（ 2-chloroethyl ）-1- nitrosourea, BCNU） dose in phosphate-buffered solution （PBS） from BCNU-loaded （polylactic-co-glycolic acid, PIGA） microspheres and to study the releasing kinetics of BCNU-PIGA microspheres in vitro. Methods BCNU concentration was detected by an ultraviolet （UV） detector at 237 nm with a Hypersil ODS2 C18 column （5 μm, 4.6mm × 150 mm）. The mixture of methanol and water （50 ： 50） was used as the mobile phase. The flow rate was 1.0 ml/min. Results The calibration curve was linear within the range of 0. 005 ～ 0.35 μmol/ml and the measurable lowest limit was 0.005 μmol/ml. The average recovery rate of BCNU at the concentrations of 0.03, 0. 1 and 0. 3 μmol/ml was 103.33%, 101.43% and 102. 04% respectively. The relative standard deviation （RSD） of the within-day and between-days variation was less than 4% and 1% respectively. The results showed that the microspheres could release BCNU for over 3 weeks. Conclusion This high performance liquid chromatography method is simple, sensitive and accurate. It is suitable for released kinetics study of controlledrelease microspheres of BCNU loading in vitro.

关 键 词：聚乳酸/羟基乙酸 卡氮芥 高效液相色谱法 药物释放动力学 

分 类 号：R979.1[医药卫生—药品]