HPLC-MS/MS法同时测定精神分裂症患者血浆中奥氮平和阿立哌唑的浓度与应用

Simultaneous determination of olanzapine and aripiprazole in plasma of schizophrenic patients by HPLC-MS/MS and its clinical application

目的建立高效液相色谱串联质谱法(HPLC-MS/MS)同时测定精神分裂症患者的奥氮平和阿立哌唑的血药浓度,用于监测精神分裂症患者的血药浓度并分析其结果。方法以咖啡因为内标,用甲醇沉淀蛋白法处理血浆样品,流动相为甲醇(A)-2%甲酸水(B),梯度洗脱,流速为0.4 mL·min^-1。用电喷雾电离源,正离子模式,多离子反应监测扫描。考察该方法的专属性、标准曲线、定量下限、精密度、回收率、基质效应和稳定性。选取20例精神分裂症患者,口服奥氮平(10 mg·d^-1)和阿立哌唑(20 mg·d^-1),于服药2周后,清晨服药前抽血2 mL。用HPLC-MS/MS法测定患者血浆中奥氮平和阿立哌唑的浓度,并对检测结果进行分析。结果奥氮平在1.00~100.00 ng·mL^-1线性关系良好(r=0.9865),最低定量下限为1.00 ng·mL^-1;阿立哌唑在10.00~800.00 ng·mL^-1线性关系良好(r=0.9998),最低定量下限为10.00 ng·mL^-1。日内、日间RSD均小于15%,提取回收率为95.67%~104.27%(RSD<15%,n=6),基质效应为98.89%~101.63%。监测20例患者显示,其中15%患者奥氮平血药浓度偏高,20%患者阿立哌唑血药浓度偏高。结论本方法简便、快速、灵敏度高、专属性好,可以提高检测效率,降低医疗成本;临床上有必要对联用奥氮平和阿立哌唑的患者早期开展血药浓度监测,以便及时调整用药方案,确保其用药安全有效。

Objective To establish a high performance liquid chromatography-tandem mass spectrometry(HPLC-MS/MS)method for simultaneous determination of olanzapine and aripiprazole plasma concentrations in schizophrenic patients,analyze the results.Methods Plasma samples were treated by the protein precipitation method with methanol as the internal standard using caffeine.The mobile phase was methanol(A)-2%formic acid water(B),gradient elution,and the flow rate was 0.4 mL·min^-1.Use electrospray ionization source,positive ion mode,multi-ion reaction monitoring scan.To investigate the specificity,standard curve,lower limit of quantification,precision,recovery rate,matrix effect and stability of the method.Twenty schizophrenic patients were selected,and oral olanzapine(10 mg·d^-1)and aripiprazole(20 mg·d^-1),2 weeks after taken the medicine,blood 2 mL was drawn before taking the medicine in the morning.HPLC-MS/MS method was used to determine the concentration of olanzapine and aripiprazole in patients’plasma,and the detection results were analyzed.Results Olanzapine had a good linear relationship in 1.00-100.00 ng·mL^-1(r=0.9865),and the minimum lower limit of quantification was 1.00 ng·mL^-1;aripiprazole had a good linear relationship in 10.00-800.00 ng·mL^-1(r=0.9998),the lowest limit of quantification was 10.00 ng·mL^-1.The intra-day and inter-day RSD were less than 15%,the extraction recovery rate was 95.67%-104.27%(RSD<15%,n=6),and the matrix effect was 98.89%-101.63%.Monitoring of 20 patients showed that 15%of the patients had high olanzapine blood concentration and 20%had high aripiprazole blood concentration.Conclusion The method in this article is simple,rapid,high sensitivity,and good specificity,which can improve the detection efficiency and reduce medical costs;clinically it is necessary to carry out early monitoring of blood drug concentration in patients with olanzapine and aripiprazole in order to adjust the drug regimen in time To ensure that its medication is safe and effective.