摘要
建立了液相色谱-串联质谱法测定Beagle犬血浆中的盐酸沙格雷酯(1),并考察1缓释胶囊的生物利用度。采用XTerra C18色谱柱,以甲醇∶10 mmol/L乙酸铵溶液(70∶30,p H 4.0)为流动相,以阿立哌唑为内标,采用ESI源、正离子模式、多反应监测扫描,监测离子对为m/z 430.1→m/z 135.1(1)和m/z 448.0→m/z 285.0(内标)。血浆中1在0.5~5 000 ng/ml范围内线性关系良好,日内RSD≤4.31%,日间RSD≤6.24%。8只Beagle犬随机交叉单剂量口服100 mg 1片(参比制剂)或150 mg缓释胶囊(受试制剂)的主要药动学参数为:cmax(3 736.45±335.68)和(1 263.78±228.83)ng/ml,AUC0→t(4 132.28±925.82)和(5 044.62±1 057.11)ng·h·ml-1,tmax(0.9±0.2)和(2.9±0.4)h,MRT(1.45±0.22)和(3.80±0.34)h。受试制剂的相对生物利用度为81.6%。
A LC-MS/MS method was established for the determination of sarpogrelate hydrochloride(1) in Beagle dog plasma, and the bioavailability of 1 sustained-release capsules was investigated. An XTerra C18 column was used with the mobile phase of methanol∶10 mmol/L ammonium acetate solution(70∶30, p H 4.0). Aripiprazole was used as the internal standard. Detection was performed on ESI positive ion by multiple reaction monitoring(MRM) mode with the transitions of m/z 430.1→m/z 135.1(1) and m/z 448.0→m/z 285.0(aripiprazole). It was linear in the range of 0.5- 5 000 ng/ml. The intra- and inter-day RSDs were no more than 4.31% or 6.24%. A randomized crossover design was performed in 8 Beagle dogs. A single oral dose of 1 tablets(reference formulation, 100 mg) or 1 sustained-release capsules(test formulation, 150 mg) was administrated. The main pharmacokinetic parameters of the reference tablets and the test capsules were as follows: cmax(3 736.45±335.68) and(1 263.78±228.83)ng/ml, AUC0→t(4 132.28±925.82)and(5 044.62±1 057.11)ng·h·ml-1, tmax(0.9±0.2) and(2.9±0.4)h, MRT(1.45±0.22) and(3.80±0.34)h. The relative bioavailability of the test formulation was 81.6%.
出处
《中国医药工业杂志》
CAS
CSCD
北大核心
2014年第12期1166-1169,共4页
Chinese Journal of Pharmaceuticals