液相色谱-质谱联用法测定双相情感障碍患者血浆中富马酸喹硫平的药物浓度

Liquid Chromatography-mass Spectrometry for Determining Plasma Quetiapine Fumarate in Patients with Bipolar Disorders

目的:开发一种简单快速测定富马酸喹硫平在双相情感障碍患者血浆中药物浓度的液相色谱-质谱联用法。方法:色谱柱Waters ACQUITY UPLC BEH C18柱(3.0 mm×50 mm,2.5μm),流动相为0.1%甲酸乙腈溶液(A)-0.1%甲酸水溶液(B),梯度洗脱;流速0.6 mL·min^(-1);柱温40℃;进样器温度10℃;进样量2μL。精密吸取血浆样品50μL,加入含有内标溶液的样品萃取液200μL,涡旋混合90 s,12000 r·min^(-1)离心10 min,吸取上清液,经0.22μm针头式过滤器过滤后进样测定,采用内标法进行定量分析。结果:喹硫平的血药浓度在50~1000 ng·mL^(-1)的范围内线性关系良好(Y=0.00583X-0.0321,r=0.9996)。LLOQ、LQC、MQC和HQC的日内和日间精密度的RSD值均<15.0%,准确度在理论浓度的±10%内,提取回收率,RSD值均<15.0%,室温、短期、长期和冻融冻存稳定性均较好(RSD<15%)。114例患者的平均血药浓度为(53.68±120.45)ng·mL^(-1)。结论:该方法灵敏度高、特异性强,能够满足临床实时准确快速检测富马酸喹硫平血药浓度的需求。

Objective:Development and validation of a simple and rapid liquid chromatography-mass spectrometry(LC-MS/MS)method for the determination of quetiapine fumarate in plasma of patients with depression.Methods:The LC-MS/MS method was applied on a Waters ACQUITY UPLC BEH C18 Column(3.0 mm×50 mm,2.5μm)with 0.1%formate in acetonitrile(A)-0.1%formic acid in water(B)for gradient elution at 0.5 mL·min^(-1),column temperature at 40°C injector temperature at 10°C and injection volume at 2μL.The accurately aspirated 50μL of plasma sample was added with 200μL of sample extract solution containing internal standard,vortex mixed for 90 s and centrifugated at 12000 r·min^(-1)for 10 min,then the supernatant was aspirated,filtered through a 0.22μm syringe filter and injected for quantitative analysis with an internal standard method.Results:The plasma concentrations of quetiapine were linearly determined in the range of 50-1000 ng·mL^(-1)(Y=0.00583X-0.0321,r=0.9996).The RSD values of intraday and inter-day precision of LLOQ,LQC,MQC and HQC were<5.0%,the accuracy was within±15%of the theoretical concentration,the extraction recovery rate was 98.65%-101.18%with RSD<5.0%,and the stability at room temperature,short-term,long-term and freeze-thaw cryopreservation were good(RSD<10%).The mean plasma concentration of 114 patients was(53.68±120.45)ng·mL^(-1).Conclusion:The LC-MS/MS method is simple to preprocess,has high analytical sensitivity and strong specificity,and can meet the needs of real-time,accurate and rapid detection of plasma quetiapine fumarate in clinical practice.