摘要
目的建立测定人血浆中辛伐他汀浓度的超高效液相色谱-串联质谱（UPLC-MS/MS）法,并将其应用于辛伐他汀片的药物动力学和生物等效性研究。方法生物等效性试验采用随机分组,两周期交叉设计,18名健康男性志愿者单剂量口服40 mg辛伐他汀受试制剂或参比制剂。血浆样品经液液萃取,其血药浓度采用所建立的UP-LC-MS/MS测定。结果本法测定血浆中辛伐他汀的线性范围为0.134～17.920 ng.mL-1,其日内及日间精密度RSD均在7.3%之内。志愿者单次服用40 mg辛伐他汀受试制剂和参比制剂后的药动学参数AUC0～12分别为（37.321±16.411）和（36.213±15.374）ng.h.mL-1,Cmax分别为（9.585±5.225）和（9.582±4.513）ng.mL-1,tmax分别为（1.86±0.56）和（1.81±0.64）h。相对生物利用度为103.02%±13.79%。结论所建立的UPLC-MS/MS法快速、灵敏、准确,所研究的2种辛伐他汀片生物等效。
Objective To develop an ultra performance LC-tandem mass spectrometry （UPLC-MS/MS） method to study the pharmacokinetics and bioequivalence of simvastatin tablets in human. Methods A single oral dose of 40 mg simvastatin tablets （test preparation and reference preparation） were administrated to 18 healthy male volunteers according to a randomized cross design. The concentration of simvastatin in the plasma was determined by UPLC-MS/ MS after a simple liquidqiquid extraction. Results The linear calibration curve of simvastatin was obtained at 0. 134～ 17. 920 ng·mL^-1. The intraday and interday precision was less than 7.3%. The pharmacokinetic parameters of the test preparation and reference preparation were as follows.- AUC0-12 was （37. 321 ±16. 411） and （36. 213±15. 374） ng. h- mL-1 Cmax was （9. 585±5. 225） and （9. 582±4. 513） ng·mL-1, andtmax was （1.86±0.56） and （1.81± 0. 64） h, respectively. The relative bioavailability of the test preparation was （103.02± 13.79）%. Conclusion This method is rapid, highly sensitive and accurate, and suitable for the pharmacokinetic study of simvastatin. The two preparations are bioequivalent.
出处
《中南药学》
CAS
2009年第7期489-493,共5页
Central South Pharmacy
