论文部分内容阅读
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 liquid chromatography-tandem mass spectrometry was developed for the determination of sarpogrelate hydrochloride in plasma of Beagle dogs (1). The bioavailability of 1 sustained-release capsules was also investigated. Using XTerra C18 column with methanol: 10 mmol / L ammonium acetate solution (70:30, p H 4.0) as mobile phase and aripiprazole as internal standard, ESI source, positive ion mode and multiple reaction monitoring , The monitored ion pairs were m / z 430.1 → m / z 135.1 (1) and m / z 448.0 → m / z 285.0 (internal standard). The linearity of plasma 1 in the range of 0.5-5000 ng / ml was good, with RSD ≤4.31% and daytime RSD ≤6.24%. The main pharmacokinetic parameters of 8 single Beagle dogs randomized crossover single oral dose of 100 mg tablets (reference) or 150 mg sustained release capsules (test): cmax (3 736.45 ± 335.68) and (1 263.78 ± 228.83 (1.45 ± 0.22) ng / ml, AUC0 → t (4 132.28 ± 925.82) and (5 044.62 ± 1057.11) ng · h · ml- And (3.80 ± 0.34) h. The relative bioavailability of the test preparation was 81.6%.