胶束液相色谱法测定山莨菪碱的血药浓度和药代动力学参数

STUDIES ON THE DETERMINATION OF PLASMA LEVEL AND PHARMACOKINETIC PARAMETERS OF ANISODAMINE BY MICELLAR LIQUID CHROMATOGRAPHY

用胶束液相色谱技术以十二烷基硫酸钠(SDS)为表面活性剂,正丙醇为改性剂,硫酸阿托品为内标,用甲醇初步沉淀蛋白后,不经萃取,直接注射血浆样品,成功地测定了山茛菪碱的体内血药浓度;进行了健康受试者肌注给药的药代动力学研究。方法准确、灵敏、简便,可供进一步研究山茛菪碱及其生物利用度等测定血药浓度,并可用于临床监测。

Anisodamine is a tropane alkaloid isolated from the plant Anisodus,tanguticus, (Max-im) Pasch. It is an anticholine drug widely used in clinics. Micellar liquid chromatography is a newtype of HPLC developed in the 1980's. Direct plasma injection technique is the application of micellarHPLC in bioanalyses. In this paper, a micellar HPLC method, which employs n-propanol as modifier, SDS as surfac-tant, atropine sulphate as internal standard, has been developed. By direct injection, this method wassuccessfully applied to the measurement of plasma level of anisodamine. Application of this method tothe study of anisodamine pharmacokinetics was investigated in human volunteers following a single in-tramuscular injection. The separation was performed in a Shim--pack CLC--CN column (150 mm×6mm ID, 5μm)with a mobile phase of n-propanol--water(15:85) with 45 mmol/L SDS and total ion strength 70mmol/L by adding phosphate, and detected at 205 nm. The standard curve was linear over the concen-tration range of 15～750 ng plasma level (r=0.9972). The measurable lowest concentration was 10ng/ml plasma (S/N=3:1). The study of anisodamine pharmacokinetic in man was also described.