液-质联用法测定人血浆中哌罗匹隆浓度及药动学

Study on pharmacokinetics and determination of perospirone in human plasma by HPLC-MS/MS

目的:建立液-质联用(LC-MS/MS)法测定人血浆中哌罗匹隆浓度,并用于盐酸哌罗匹隆片人体药动学研究。方法:HPLC-MS/MS系统由Waters公司2695型HPLC仪和Quattro Premier XE MircoMass型三重四级杆串联质谱仪组成,以Waters XTerraMS C18柱(2.1 mm×150 mm,5μm)为分析柱,流动相为10 mmol·L-1醋酸铵-乙腈(20∶80)。血浆样品用液液萃取法处理,以多反应离子监测,非那雄胺为内标。利用该方法进行了盐酸哌罗匹隆单、多次给予8 mg及单次给予16 mg的药动学研究。结果:哌罗匹隆在0.1～30μg·L-1范围内线性良好,最低定量限为0.1μg·L-1,方法回收率86.67%～108.86%,萃取回收率70.29%～94.11%,日内和日间精密度分别为4.06%～11.15%和8.18%～8.64%。经时血药浓度数据用DAS软件进行药动学拟合,表明盐酸哌罗匹隆的体内过程符合二室模型,且在考察剂量范围内,呈线性动力学过程。单次口服给药8 mg的tmax为(1.00±0.00)h,Cmax为(14.4±2.1)μg·L-1,AUC0-t为(34.3±8.2)μg·L-1.h;单次口服给药16 mg的tmax为(1.10±0.21)h,Cmax为(23.7±4.3)μg·L-1,AUC0-t为(60.8±11.0)μg·L-1·h;多次口服给药8 mg的tmax为(0.95±0.16)h,Cmax为(13.9±2.4)μg·L-1,AUC0-t为(35.8±10.6)μg·L-1·h,多次给药后蓄积因子为1.35。结论:该方法灵敏、准确、快速、特异性强,适用于盐酸哌罗匹隆的药动学研究。

OBJECTIVE To developa HPLC-MS/MS method for determination and study of the pharmacokinetics of perospirone in human plasma.METHODS HPLC-MS/MS system consisted of Waters 2695 HPLC instrument and Quattro Premier XE MircoMass triple quadrupole tandem mass spectrometer.The analyte was separated on a Waters XTerra MS C18 column（2.1 mm 150 mm,5 μm） with a mobile phase of acetonitrile and water containing 10 mmol·L^-1 ammonium acetate（80∶20）.The plasma samples were extracted by liquid-liquid extraction,and the multiple reaction monitoring was used for quantification,finasteride was used as internal standard.After that,pharmacokinetic study of perospirone hydrochloride was done after single and multiple administration of 8 mg and single administration of 16 mg perospirone hydrochloride tablets.RESULTS The linear range was 0.1-30 μg·L^-1,and the limit of detection was 0.1 μg·L^-1.The methodology recovery was 86.67%-108.86%,extraction recovery was 70.29%-94.11%,intra-and inter-assay precision was 4.06%-11.15% and 8.18-8.64%.The concentration-time data of perospirone were treated with DAS pharmacokinetic software and fitted as a two-compartment model,and there was linear kinetic process within tested dose range.Single dose administration of 8 mg： tmax was（1.00±0.00） h,Cmax was（14.4±2.1） μg·L^-1,AUC0-t was（34.3±8.2） μg·L^-1·h;single dose administration of 16 mg： tmax was（1.10±0.21） h,Cmax was（23.7±4.3） μg·L^-1,AUC0-t was（60.8±12.0） μg·L^-1·h;multiple dose administration of 8 mg： tmax was（0.95±0.16） h,Cmax was（13.9±2.4） μg·L^-1,AUC0-t was（35.8±10.6）μg·L^-1·h,accumulation factor was 1.35 after multiple dosing.CONCLUSION The method is proved to be sensitive,accurate,rapid,specific and suitable for the clinical pharmacokinetic study of perospirone hydrochloride tablets.