论文部分内容阅读
目的:建立测定犬血浆中阿托伐他汀钙浓度的高效液相-质谱串联(LC-MS/MS)方法,并用于阿托伐他汀钙缓释肠溶胶囊的生物等效性考察。方法:采用随机、开放、双交叉实验设计,8只Beagle犬单剂量口服阿托伐他汀钙受试制剂和参比制剂80 mg,采用LC-MS/MS法测定犬血浆中阿托伐他汀钙的浓度,用DAS软件计算主要药动学参数,并评价2种制剂的生物等效性。结果:该方法的线性范围为0.25~75 ng·ml-1(r=0.999 9),最低定量可达0.25 ng·ml-1,平均提取回收率和日内、日间精密度均符合方法学研究要求。受试制剂的AUC为参比制剂的82.9%,Cmax明显低于参比制剂,tmax延迟,且受试制剂的MTR、t1/2大于参比制剂,该制剂具有缓释特性,因此阿托伐他汀钙参比制剂与受试制剂生物等效。结论:该方法操作简单、灵敏、准确,适用于阿托伐他汀钙血药浓度的测定及生物等效性考察。
Objective: To establish a high performance liquid chromatography-tandem mass spectrometry (LC-MS / MS) method for the determination of atorvastatin calcium concentration in canine plasma and to evaluate the bioequivalence of atorvastatin calcium-controlled enteric-coated capsules. Methods: Randomized, open and double-crossover experimental design, eight Beagle dogs were orally administered with atorvastatin calcium 80 mg and reference substance 80 mg respectively, and the plasma concentrations of atorvastatin calcium The main pharmacokinetic parameters were calculated using the DAS software and the bioequivalence of the two formulations was evaluated. Results: The linear range of this method was 0.25-75 ng · ml-1 (r = 0.999 9) with the lowest quantification of 0.25 ng · ml-1. The average extraction recovery and intra- and inter-day precision were in accordance with the methodology Claim. The AUC of the test formulation was 82.9% of the reference formulation, the Cmax was significantly lower than the reference formulation, the tmax was delayed, and the MTR, t1 / 2 of the test formulation was greater than that of the reference formulation with sustained release characteristics, Statin calcium reference formulation is bioequivalent to the test formulation. Conclusion: The method is simple, sensitive and accurate, suitable for the determination of atorvastatin calcium concentration and bioequivalence study.