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UFLC-MS/MS法测定人胎盘灌流液中氟西汀、去甲氟西汀、舍曲林的浓度及其胎盘透过率
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| 篇名： | UFLC-MS/MS法测定人胎盘灌流液中氟西汀、去甲氟西汀、舍曲林的浓度及其胎盘透过率 |
| TITLE： | Determination of fluoxetine ，norfluoxetine and sertraline concentration in human placental perfusate and their placental permeability by UFLC-MS/MS |
| 摘要： | 目的 建立测定人胎盘灌流液中氟西汀、去甲氟西汀、舍曲林浓度的方法并测定胎盘透过率。方法以格列本脲为内标，采用蛋白沉淀法对样品进行前处理，采用超快速液相色谱-串联质谱（UFLC-MS/MS）法检测。以SynergiTMHydro-RP80ALC为色谱柱，以水（含0.1％甲酸）-乙腈（含0.1％甲酸）为流动相进行梯度洗脱，流速为0.70mL/min，柱温为40℃，进样量为5μL。采用电喷雾离子源，以多反应监测模式进行正离子扫描，用于定量分析的离子对分别为m/z309.9→148.1（氟西汀）、m/z296.0→134.4（去甲氟西汀）、m/z306.1→159.0（舍曲林）、m/z493.9→369.1（内标）。建立单个胎盘小叶双向循环灌注模型，在母体侧胎盘灌流液中加入氟西汀（160ng/mL）、去甲氟西汀（160ng/mL）、舍曲林（100ng/mL）和安替比林（阳性对照，100ng/mL），采用上述UFLC-MS/MS法于循环0、10、20、30、45、60、90、120、150、180min时分别测定氟西汀、去甲氟西汀、舍曲林的浓度并计算胎盘透过率。结果氟西汀、去甲氟西汀、舍曲林检测质量浓度的线性范围均为5.00～500ng/mL（r均大于0.990），定量下限均为5.00ng/mL；日内、日间RSD均不高于14.0％，相对误差为－9.6％～14.7％；稳定性试验的相对误差为－4.0％～11.0％；残留效应、提取方法、基质效应均不影响待测成分的定量分析。成功建立人胎盘体外循环灌注模型31个，其中15个为氟西汀、去甲氟西汀灌流，10个为舍曲林灌流，6个为安替比林灌流。灌流3h后，氟西汀、去甲氟西汀、舍曲林的平均胎盘透过率分别为（8.74±1.67）％、（10.70±4.81）％、（5.90％±1.25）％。结论所建UFLC-MS/MS法操作简便、灵敏度和准确度均较高，可用于测定人胎盘灌流液中氟西汀、去甲氟西汀及舍曲林的浓度。氟西汀、去甲氟西汀、舍曲林均可透过胎盘，但舍曲林的胎盘透过率更低。 |
| ABSTRACT： | OBJECTIVE To establish t he method for determining the concentrations of fluoxetine ，norfluoxetine and sertraline in human placental perfusate method and their placental permeability. METHODS Using glyburide as internal standard ，the samples were pretreated by protein precipitation method and detected by ultra-fast liquid chromatograph-mass spectrometer/mass spectrometer （UFLC-MS/MS）. The determination was performed on Synergi TM Hydro-RP 80A LC column with mobile phase consisted of water （containing 0.1％ formic acid ）-acetonitrile（containing 0.1％ formic acid ）at the flow rate of 0.70 mL/min，with a gradient elution. The column temperature was set at 40 ℃，and sample size was 5 μL. Detection was performed with electrospray ionization source in multipl e reaction monitoring mode . The ion pairs for quantitative analysis we re m/z 309.9→148.1（fluoxetine），m/z 296.0→134.4 （-167）， （norfluoxetine），m/z 306.1→159.0 （sertraline），m/z 493.9→ No.2018FE001（-207），（internal standard ）. The perfusion model of singal placenta under bidrectional cardiopulmonary bypass was established. Fluoxetine （160 ng/mL），norfluoxetine（160 ng/mL）， sertraline（100 ng/mL）and antipyrine （positive control ，ng/mL）were added into the maternal perfusate. The concen- 65324888 trations of fluoxe tine， norfluoxetine and sertrali ne were measured by above UFLC-MS/MS at 0，10，20，30，45，60，90，120，150 and 180 min of circulation ，and the placental permeability was calculated. RESULTS The linear range of fluoxetine ，norfluoxetine and sertraline were 5.00-500 ng/mL（all r＞ 0.990），and the lower limits of quantification were all 5.00 ng/mL. The RSDs of intra-day and inter-day were all less than 14.0％， and relative error ranged －9.6％ to 14.7％. The relative error of stability test was －4.0％ to 11.0％；the residual effect ，extraction method and matrix effect did not affect the quantitative analysis of the substance to be tested. Totally 31 perfusion model of human placenta under cardiopulmonary bypass were successfully established ，including 15 fluoxetine and norfluoxetine perfusion ，10 sertraline perfusion and 6 antipyrine perfusion. After 3 hours of perfusion ，the average placental permeability of fluoxetine ， norfluoxetine and sertraline were （8.74 ± 1.67）％ ，（10.70 ± 4.81）％ ，（5.90 ± 1.25）％ ，respectively. CONCLUSIONS The established UPLC-MS/MS is simple ，sensitive and accurate. It can be used for determination of fluoxetine ，norfluoxetine and sertraline in human placental perfusate. Fluoxetine ，norfluoxetine and sertraline can pass through the placenta ，but sertraline has a lower placental permeability. |
| 期刊： | 2022年第33卷第02期 |
| 作者： | 王晶晶，黄桦，晏林，高杉，李骞，王丹，张峻 |
| AUTHORS： | WANG Jingjing ，HUANG Hua，YAN Lin，GAO Shan，LI Qian，WANG Dan，ZHANG Jun |
| 关键字： | 氟西汀；去甲氟西汀；舍曲林；超快速液相-串联质谱法；胎盘灌流；胎盘透过率 |
| KEYWORDS： | fluoxetine； norfluoxetine； sertraline； ultra-fast liquid chromatograph-mass spectrometer/mass spectrometer ； |
| 阅读数： | 316 次 |
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