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基于干血浆斑的 LC-MS/MS 法监测治疗患者血液中的美罗培南。

Dried Plasma Spot Based LC-MS/MS Method for Monitoring of Meropenem in the Blood of Treated Patients.

机构信息

Department of Medicine Laboratory, The First Hospital of Jilin University, Jilin University, Changchun 130061, China.

Department of Breast Disease, The Second Hospital of Jilin University, Jilin University, Changchun 130061, China.

出版信息

Molecules. 2022 Mar 19;27(6):1991. doi: 10.3390/molecules27061991.

DOI:10.3390/molecules27061991
PMID:35335353
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8949976/
Abstract

Meropenem (MER) is widely used to treat complicated and serious infections. Therapeutic drug monitoring (TDM) provides a valid clinical tool to avoid suboptimal concentrations and dose−related adverse reactions. However, TDM seems to face challenges since the limited stability of MER in plasma makes transport difficult between clinics and laboratories. Dried plasma spot (DPS) sampling is an attractive but underutilized method for TDM that has the desired features of easy collection, storage, and transport, and overcomes known hematocrit (HCT) issues in dried blood spot (DBS) analysis. This study was designed to investigate a DPS−based liquid chromatography−tandem mass spectrometry (LC−MS/MS) method for quantification of MER. The method was developed and validated for DPS and wet plasma samples. Calibration curves were linear (R2 > 0.995) over the concentration range of 0.5−50 µg/mL. Overall accuracy and precision did not exceed 15% and no significant matrix effect was observed. MER has been more stable in DPS than in wet plasma samples. A comparison of DPS and wet plasma concentrations was assessed in 32 patients treated with MER. The results showed that there was no significant difference between the two methods. So the DPS method developed in this study is appropriate and practical for the monitor of MER in the daily clinical laboratory practice.

摘要

美罗培南(MER)被广泛用于治疗复杂和严重的感染。治疗药物监测(TDM)提供了一种有效的临床工具,可以避免浓度不足和剂量相关的不良反应。然而,TDM 似乎面临挑战,因为 MER 在血浆中的有限稳定性使得在诊所和实验室之间的运输变得困难。干血浆斑(DPS)采样是一种有吸引力但未充分利用的 TDM 方法,具有易于采集、储存和运输的理想特点,并克服了干血斑(DBS)分析中已知的红细胞压积(HCT)问题。本研究旨在研究基于 DPS 的液相色谱-串联质谱(LC-MS/MS)方法用于定量测定 MER。该方法是为 DPS 和湿血浆样品开发和验证的。校准曲线在 0.5-50 µg/mL 的浓度范围内呈线性(R2 > 0.995)。总体准确度和精密度不超过 15%,未观察到明显的基质效应。与湿血浆样品相比,MER 在 DPS 中更稳定。在接受 MER 治疗的 32 名患者中评估了 DPS 和湿血浆浓度之间的比较。结果表明,两种方法之间无显著性差异。因此,本研究中开发的 DPS 方法适用于日常临床实验室实践中 MER 的监测。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6142/8949976/5382385561f1/molecules-27-01991-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6142/8949976/3f6cdc731317/molecules-27-01991-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6142/8949976/b88484f053f0/molecules-27-01991-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6142/8949976/7573fbf1a01b/molecules-27-01991-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6142/8949976/5382385561f1/molecules-27-01991-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6142/8949976/3f6cdc731317/molecules-27-01991-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6142/8949976/b88484f053f0/molecules-27-01991-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6142/8949976/7573fbf1a01b/molecules-27-01991-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6142/8949976/5382385561f1/molecules-27-01991-g004.jpg

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