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一种改良的简单 LC-MS/MS 方法,用于测量血清中的阿立哌唑及其主要代谢物。

An improved simple LC-MS/MS method for the measurement of serum aripiprazole and its major metabolite.

机构信息

NESMOS (Neuroscience, Mental Health, and Sensory Organs) Department, School of Medicine and Psychology, Sapienza University, Sant'Andrea Hospital, Rome,

出版信息

J Pharm Biomed Anal. 2012 Mar 25;62:135-9. doi: 10.1016/j.jpba.2012.01.003. Epub 2012 Jan 14.

Abstract

BACKGROUND AND OBJECTIVES

Current liquid chromatographic tandem mass spectrometry (LC-MS/MS) methods to measure serum levels of aripiprazole (Ar) and dehydroaripiprazole (DHAr) are sensitive, but difficult to use in a hospital context. We aimed to develop a rapid LC-MS/MS method allowing reliable level measurement in the presence of co-administered drugs, withdrawing samples from 22 patients with acute agitation receiving 9.75 mg aripiprazole IM injection.

METHOD

We developed a sensitive and selective HPLC-MS/MS method to measure serum Ar and DHAr levels in a hospital laboratory, requiring minimal sample preparation and inferior sample volume compared to previous LC-MS/MS methods. Analytes were separated on a reversed-phase HPLC (run-time, 10 min). A triple quadrupole tandem mass spectrometer was used for quantitative analysis in positive mode by a multiple reaction monitoring. Samples were drawn 2, 4, 6, and 24h post-injection.

RESULTS

Calibration curves (2-1000 ng/mL for Ar and 3.5-500 ng/mL for DHAr) were linear, with mean correlation coefficient >0.9998. Within- and between-day precision and accuracy were within 10%. Mean recovery was 95.2 ± 4.5% for Ar and 97.6 ± 7.2% for DHAr. Ar and DHAr peaks were not affected by other co-administered psychotropic drugs.

CONCLUSION

Our method measured Ar and DHAr concentrations reliably, simply and rapidly without employing many reagents, as currently existing methods.

摘要

背景与目的

目前用于测量血清中阿立哌唑(Ar)和脱氢阿立哌唑(DHAr)水平的液相色谱串联质谱(LC-MS/MS)方法虽然灵敏,但在医院环境中难以使用。我们旨在开发一种快速 LC-MS/MS 方法,以便在合并用药的情况下可靠地测量其浓度,从 22 名接受 9.75mg 阿立哌唑肌内注射治疗急性激越的患者中采集样本。

方法

我们在医院实验室中开发了一种灵敏且具有选择性的 HPLC-MS/MS 方法来测量血清中 Ar 和 DHAr 的浓度,与之前的 LC-MS/MS 方法相比,该方法需要的样品制备和样品量更少。分析物在反相 HPLC 上进行分离(运行时间 10 分钟)。三重四极杆串联质谱仪在正模式下通过多重反应监测进行定量分析。在注射后 2、4、6 和 24 小时采集样本。

结果

校准曲线(Ar 为 2-1000ng/mL,DHAr 为 3.5-500ng/mL)呈线性,平均相关系数>0.9998。日内和日间精密度和准确度均在 10%以内。Ar 的平均回收率为 95.2±4.5%,DHAr 的平均回收率为 97.6±7.2%。Ar 和 DHAr 的峰不受其他合并使用的精神药物的影响。

结论

与目前现有的方法相比,我们的方法简单、快速且无需使用大量试剂,能够可靠地测量 Ar 和 DHAr 的浓度。

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