Beagle犬血浆中盐酸沙格雷酯的LC-MS/MS法测定及缓释胶囊的生物利用度

Determination of Sarpogrelate Hydrochloride in Beagle Dog Plasma by LC-MS/MS and Bioavailability of Its Sustained-release Capsules

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%.