液相色谱-质谱联用法研究大鼠血浆及纹状体中罗匹尼罗药动学

Pharmacokinetics of ropinirole determined by LC-MS / MS in rat plasma and striatum

目的：通过大鼠血浆及纹状体组织匀浆中罗匹尼罗的液相色谱-质谱联用（LC-MS/MS）检测方法,研究其在血浆和纹状体的药动学特征。方法：通过LC-MS/MS检测分析血浆和纹状体组织匀浆样品。大鼠尾静脉注射罗匹尼罗（0.27 mg·kg-1）,分别于给药前和给药后不同时间点采集血浆、制备纹状体组织匀浆样品,测定浓度,计算血浆药动学参数,考察纹状体分布特征。结果：血浆和组织匀浆中罗匹尼罗在1~100ng·m L-1浓度范围内线性关系良好（r2〉0.99）。罗匹尼罗在大鼠血浆中消除半衰期t1/2为（0.49±0.30）h,药-时曲线下面积AUC0~∞为（29.48±11.49）ng·h·m L-1,纹状体中消除半衰期t1/2为（0.29±0.04）h,药-时曲线下面积AUC0~∞为（75.66±16.06）ng·h·g-1,其浓度随血药浓度下降而下降。结论：该方法重复性好、灵敏度高、特异性强。罗匹尼罗可迅速透过血脑屏障并在纹状体富集,是一种高效多巴胺D2受体激动剂。

Objective： To develop an LC-MS/MS method for quantification of ropinirole in the plasma and striatum of rats, and to investigate its pharmacokineties. Methods： Plasma and striatum homogenate samples were analyzed by LC-MS/MS. Ropinirole （0.27 mg·kg-1） was intravenously injected to SD rats. Blood samples and striatum homogenates were obtained before and after dosing at selected intervals. The concentrations were deter- mined, and pharmaeokinetics and distribution properties were analyzed. Results： The calibration curves were line ar over the range of 1 - 100 ng- mL-l in both plasma and striatum homogenates （r2 〉 0.99）. The pharmacokinetic parameters of ropinirole were as follows ： in plasma, t1、2 （0.49 ± 0.30 ） h and AUC. （29.48 ± 11.49 ） ng· h·mL - 1 ; in striatum, t2/2 （0.29 ± 0.04 ） h and AUC0-∞（75.66± 16.06 ） ng· h· g - 1. Distribution kinetics in the stri- atum was similar to the concentration changes in plasma. Conclusion： This validated method is simple and quick, with high repeatability, specificity and sensitivity. As a dopamine D2 receptor agist, ropinirole is readily able to cross the blood-brain barrier and enriched in the striatum.