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改良 HPLC 法测定 COVID-19 患者红细胞中利巴韦林浓度及其应用。

Improved HPLC method for the determination of ribavirin concentration in red blood cells and its application in patients with COVID-19.

机构信息

Department of Pharmacy, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China.

Department of Respiratory Medicine, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China.

出版信息

Biomed Chromatogr. 2022 Jul;36(7):e5370. doi: 10.1002/bmc.5370. Epub 2022 Mar 31.

DOI:10.1002/bmc.5370
PMID:35297066
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9073979/
Abstract

Ribavirin is a synthetic, broad-spectrum antiviral drug. Ribavirin is recommended as an antiviral drug in the Interim Guidance for Diagnosis and Treatment (the seventh edition) of COVID-19. The ribavirin levels in red blood cells may be closely related to both its efficacy and adverse drug reactions. In this study, a simple and fast HPLC-UV method was established to determine the concentrations of total ribavirin in the red blood cells of 13 patients with COVID-19. Phosphorylated ribavirin was dephosphorylated by phosphatase incubation to obtain the total amount of ribavirin in red blood cells. The chromatographic column was an Atlantis C . The recoveries were 85.45-89.05% at three levels. A good linear response was from 1 to 200 μg/ml, with a correlation coefficient of r  = 0.9991. The concentration of total ribavirin in the red blood cells of the patients ranged from 30.83 to 133.34 μg/ml. The same samples without phosphatase incubation ranged from 4.07 to 20.84 μg/ml. About 85% of ribavirin was phosphorylated in red blood cells. In addition, we observed changes in these patients' hematological parameters and found that the erythrocyte, hemoglobin and hematocrit declined to the lowest levels on the fifth day after discontinuation of ribavirin (p < 0.05).

摘要

利巴韦林是一种合成的广谱抗病毒药物。利巴韦林被推荐为《新型冠状病毒肺炎诊疗方案(试行第七版)》中的抗病毒药物。红细胞中的利巴韦林水平可能与疗效和药物不良反应密切相关。在这项研究中,建立了一种简单快速的 HPLC-UV 方法,用于测定 13 例 COVID-19 患者红细胞中利巴韦林的总浓度。用磷酸酶孵育将磷酸化的利巴韦林去磷酸化,以获得红细胞中的利巴韦林总量。色谱柱为 Atlantis C 。在三个浓度水平下,回收率为 85.45-89.05%。在 1 至 200μg/ml 范围内具有良好的线性响应,相关系数 r 为 0.9991。患者红细胞中利巴韦林总浓度范围为 30.83 至 133.34μg/ml。未经磷酸酶孵育的相同样本浓度范围为 4.07 至 20.84μg/ml。约 85%的利巴韦林在红细胞中被磷酸化。此外,我们观察了这些患者的血液学参数变化,发现利巴韦林停药后第 5 天红细胞、血红蛋白和血细胞比容降至最低水平(p<0.05)。

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本文引用的文献

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World J Hepatol. 2016 Jan 18;8(2):123-30. doi: 10.4254/wjh.v8.i2.123.
2
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J Pharm Biomed Anal. 2014 Mar;90:119-26. doi: 10.1016/j.jpba.2013.11.027. Epub 2013 Dec 1.
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J Pharm Biomed Anal. 2012 Jul;66:376-80. doi: 10.1016/j.jpba.2012.03.030. Epub 2012 Mar 28.
4
Ribavirin plasma concentration measurements in patients with hepatitis C: early ribavirin concentrations predict steady-state concentrations.丙型肝炎患者的利巴韦林血浆浓度测量:早期利巴韦林浓度可预测稳态浓度。
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Use of ribavirin to treat influenza.使用利巴韦林治疗流感。
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The use of trough ribavirin concentration to predict sustained virological response and haematological toxicity in HIV/HCV-co-infected patients treated with ribavirin and pegylated interferon.利用利巴韦林谷浓度预测接受利巴韦林和聚乙二醇干扰素治疗的HIV/HCV合并感染患者的持续病毒学应答和血液学毒性。
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