HPLC法测定比格犬血浆中的辛伐他汀及辛伐他汀羟基酸  

HPLC determination of simvastatin and simvastatin hydroxylated acid in Beagle dogs plasma

作　　者：田大丰[1] 李英[1] 莫凤奎[1] 王中彦[1] 李莉[2] 闫永波 

机构地区：[1]沈阳药科大学药学院,沈阳110016 [2]辽宁大学药学院,沈阳110036 [3]本溪市中心医院,本溪117000

出　　处：《药物分析杂志》2007年第7期989-992,共4页Chinese Journal of Pharmaceutical Analysis

摘　　要：目的:建立血浆中辛伐他汀及其主要代谢活性成分辛伐他汀羟基酸的含量测定方法。方法:以洛伐他汀为内标物质,流动相采用甲醇-水-冰醋酸(74:26:0.5),检测波长为238nm,流速为1.0mL·min^(-1)。血浆样品采用乙腈沉淀蛋白处理。并测定了10只比格犬单剂量口服辛伐他汀自乳化胶囊和市售片后的血药浓度。结果:血浆中内源性物质对辛伐他汀及辛伐他汀羟基酸的测定无干扰;最低检出限辛伐他汀为0.5ng·mL^(-1),辛伐他汀羟基酸为0.75ng·mL^(-1);辛伐他汀羟基酸在2～100ng·mL^(-1)浓度范围内线性关系良好,r=0.9989,辛伐他汀在1～50ng·mL^(-1)浓度范围内线性关系良好,r=0.9993;绝对回收率为79.68%～95.3%,方法回收率为89.1%～95.3%;日内精密度 RSD≤2.9%、日间精密度 RSD≤4.6%。结论:本方法处理简单,无干扰,灵敏度高,适合测定生物样本中的辛伐他汀及辛伐他汀羟基酸。Objective：To establish an HPLC method for determination of simvastatin and simvastatin hydroxylated acid in Beagle dogs plasma. Methods：Lovastatin was employed as an internal standard. The mobile phase consisted of methanol-water- acetic acid glacial（74： 26： 0. 5 ,v/v/v）,at the flow rate of 1.0 mL·min^-1. Protein in serum sample was precylate with acetonitrile and then detected in 238 nm wavelength. Blood samples were obtained after a single dose of 20 mg simvastatin self - microemulsifying capsules and simvastatin tablets. Results： Simvastatin and simvastatin hydroxylated acid were separated completely without interference. The calibration curves were demonstrated to be linear in the working range between 2 to 100 ng·mL^-1（ simvastatin hydroxylated acid）and between 1 to 50 ng·mL^-1 （simvastatin）. The detection limit of simvastatin in plasma was 0. 5 ng·mL^-1 and that for simvastatin hydroxylated acid was 0. 75 ng·mL^-1. The absolute recovery was 79. 68% -95.3% ,the analytical recovery was 89. 1% -95. 3% ,the within - day RSD and between - day RSD were less than 2. 9% and 4. 6% respectively. Conclusion： This method is simple and sensitive, and can be used in analyzing simvastatin in biological sample.

关 键 词：辛伐他汀 辛伐他汀羟基酸 血药浓度 药代动力学 自乳化胶囊 HPLC 

分 类 号：R917[医药卫生—药物分析学]