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UPLC-MS/MS 法同时测定人血浆中两种抗精神病药和两种抗抑郁药及其临床应用。

A UPLC-MS/MS Assay for Simultaneous Determination of Two Antipsychotics and Two Antidepressants in Human Plasma and Its Application in Clinic.

机构信息

Department of Pharmacy, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.

出版信息

Curr Pharm Biotechnol. 2020;21(1):60-69. doi: 10.2174/1389201020666190830150549.

DOI:10.2174/1389201020666190830150549
PMID:31470784
Abstract

BACKGROUND

Antidepressants and antipsychotics are widely prescribed drugs for the treatment of mental diseases. Therapeutic drug monitoring (TDM) is recommended for patients taking these drugs to ensure pharmaceutical efficacy, medication compliance and prevent toxicity.

OBJECTIVE

An ultra-high performance liquid chromatography/tandem-mass spectrometry (UPLC-MS/ MS) method was developed for simultaneous determination of two Antidepressants-Fluoxetine (FLU) and Escitalopram (ESC), and two antipsychotics-risperidone (RIS) and aripiprazole (ARI), in human plasma.

METHODS

The sample was processed by simple protein precipitation and the targeted analytes were separated on a C18 column by gradient elution with a mobile phase containing 0.1% formic acid (v/v) and acetonitrile. All the analytes were qualitative and quantitative measured by electrospray ionization source with Multiple Reaction Monitoring (MRM) in positive ion mode. A total of 56 plasma samples were obtained from out- or in-patients who were taking the cited four drugs for further analysis.

RESULTS

The calibration curves for FLU, ESC, RIS and ARI were linear in the range of 45-1800, 4-320, 2-200 and 50-1800 ng/mL, respectively. The entire analytical time for the analytes was 7.0 min for each run and the extraction efficiency was more than 90%. The sample was stable within various storage conditions. The trough concentrations in patients were measured with the validated method.

CONCLUSION

The developed method was successfully used for simultaneous determination of FLU, ESC, RIS and ARI in the plasma of the patients, which provides effective technical support for routine TDM of these four drugs and is of great clinic value for individual therapy.

摘要

背景

抗抑郁药和抗精神病药被广泛用于治疗精神疾病。建议接受这些药物治疗的患者进行治疗药物监测(TDM),以确保药物疗效、用药依从性并预防毒性。

目的

建立一种超高效液相色谱/串联质谱(UPLC-MS/MS)法,用于同时测定人血浆中的两种抗抑郁药氟西汀(FLU)和依西酞普兰(ESC),以及两种抗精神病药利培酮(RIS)和阿立哌唑(ARI)。

方法

采用简单的蛋白沉淀法处理样品,用含 0.1%(v/v)甲酸和乙腈的流动相进行梯度洗脱,在 C18 柱上分离靶向分析物。采用电喷雾电离源,正离子模式下多反应监测(MRM)进行定性和定量分析。共获得 56 份来自门诊或住院患者的血浆样本,这些患者正在服用上述四种药物进行进一步分析。

结果

FLU、ESC、RIS 和 ARI 的校准曲线在 45-1800、4-320、2-200 和 50-1800ng/mL 范围内呈线性。每个运行的分析时间为 7.0 分钟,提取效率大于 90%。样品在各种储存条件下均稳定。采用验证后的方法测定了患者的谷浓度。

结论

该方法成功用于测定患者血浆中的 FLU、ESC、RIS 和 ARI,为这四种药物的常规 TDM 提供了有效的技术支持,对个体化治疗具有重要的临床价值。

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