HPLC-MS/ESI测定人血浆中阿立哌唑的浓度

 目的建立测定人血浆中阿立哌唑的HPLC-MS,并用于研究阿立哌唑在精神分裂症患者体内的药动学。方法血浆样品中加入内标艾司唑仑,用叔丁基甲醚萃取。色谱柱为Hypersil GOLD(2.1 mm×150 mm,5μm),流动相为乙腈-30 mmol·L^-1醋酸铵缓冲液-甲酸(42∶58∶0.1),流速0.35 mL·min^-1。采用电喷雾电离源正源(ESI+),选择离子检测方式,用于定量分析的检测离子为m/z448,450(阿立哌唑)和m/z295(内标)。结果阿立哌唑在19.90～1 119.60μg·L^-1内线性关系良好(r=0.999 9),最低定量质量浓度为1.00μg·L^-1(S/N=10),方法回收率在97.2%～103.5%之间,日内与日间RSD均小于8.0%(n=5)。结论该方法灵敏度高,结果准确,适用于治疗剂量阿立哌唑体内药动学的研究。

Determination of Aripiprazole in Human Plasma by HPLC-MS/ESI

OBJECTIVE To develop a HPLC-MS method for the determination of aripiprazole in human plasma and study its pharmacokinetic parameters in schizophrenia patients.METHODS Aripiprazole and the internal standard estazolam were extracted from the patient plasma using liquid-liquid extraction by Methyl tert-butyl ether,then separated on a Hypersil GOLD column(2.1 mm×150 mm,5 μm) with a mobile phrase of acetonitrile-30 mmol·L^-1 ammonium acetate-formic acid solution(42∶58∶0.1) at a flow rate of 0.35 mL·min^-1.HPLC-MS-ESI+ was performed in the selected ion monitoring(SIM) mode using target ions at m/z 448,450(aripiprazole)and m/z 295(IS).RESULTS The linear concentration range of the calibration curves for aripiprazole was 19.90～1 119.60 μg·L^-1(r=0.999 9).The limit of quantitation of aripiprazole was 1.00 μg·L^-1(S/N=10).The average recovery was in the range of between 97.2% and 103.5%.Within-day and between-day RSDs were less than 8.0%(n=5).CONCLUSION The method is sensitive,accurate and suitable for the pharmacokinetic study of aripiprazole.