Beagle犬血浆中阿立哌唑的LC-MS/MS测定法及其在口溶膜药动学研究中的应用

Determination of Aripiprazole in Beagle Dog Plasma by LC-MS/MS and Its Application to Pharmacokinetic Study of Orodispersible Films

建立了液相色谱-串联质谱法测定Beagle犬血浆中阿立哌唑的浓度。以苯海拉明为内标,采用电喷雾电离源正离子模式、多反应监测(MRM)进行定量分析。阿立哌唑在0.1~100 ng/mL范围内线性关系良好。方法学验证结果表明,该方法回收率为97.8%~100.3%,批内RSD≤3.80%,批间RSD≤6.97%,无明显基质效应,稳定性良好。将经验证的方法应用于自制阿立哌唑口溶膜与市售阿立哌唑口腔崩解片在Beagle犬体内的药动学研究。试验结果表明,2种剂型具有相似的药动学性质,自制阿立哌唑口溶膜的相对生物利用度为(110.1±10.5)%。

A liquid chromatography coupled to tandem mass spectrometry(LC-MS/MS)method was established for determination of aripiprazole in Beagle dog plasma with diphenhydramine as the internal standard.The detection was conducted with an electrospray ionization(ESI)interface via multiple reaction monitoring(MRM)under positive ionization mode.It was linear for aripiprazole in the concentration range of 0.1-100 ng/mL.The method validation tests were carried out.The recoveries were 97.8%-100.3%,and intra-and inter-day RSDs were respectively less than 3.80%and 6.97%.No significant matrix effects were observed and the analytes were proved to be stable.This validated method was applied to the pharmacokinetics study of the self-made aripiprazole orodispersible films and the commercially available aripiprazole orally disintegrating tablets in Beagle Dogs.The results exhibited the similar pharmacokinetic characteristics between these two dosage forms and the relative bioavailability of the self-made films was(110.1±10.5)%.