Simultaneous quantification of coproporphyrin-I and 3-carboxy-4-methyl-5-propyl-2-furanpropanoic acid in human plasma using ultra-high performance liquid chromatography coupled to tandem mass spectrometry
Simultaneous quantification of coproporphyrin-I and 3-carboxy-4-methyl-5-propyl-2-furanpropanoic acid in human plasma using ultra-high performance liquid chromatography coupled to tandem mass spectrometry
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DOI：
10.1016/j.jpba.2020.113202
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发表时间：
2020-05-30
影响因子：
3.4
通讯作者：
Ohno, Keiko
中科院分区：
文献类型：
--
作者：
Suzuki, Yosuke;Sasamoto, Yuri;Ohno, Keiko
在慢性肾病（CKD）中，有机阴离子转运多肽（OATP）1B活性通过涉及3-羧基-4-甲基-5-丙基-2-呋喃丙酸（CMPF）（一种尿毒症毒素）的机制降低。粪卟啉-I（CP-I）是一种用于OATP 1B活性表型分析的敏感和特异性内源性探针，也是个体化OATP 1B底物剂量的潜在有用工具。在本研究中，我们开发并验证了一种采用高效液相色谱串联质谱法（UHPLC-MS/MS）同时定量人血浆中CP-I和CMPF的测定方法。通过固相萃取制备样品，然后进行UHPLC-MS/MS定量。该试验符合美国食品药品监督管理局（FDA）试验验证指导原则的要求，CP-I的定量下限为0. 1 ng/mL，CMPF的定量下限为50 ng/mL。CP-I和CMPF的人血浆回收率范围分别为97.3%-109.8%和94.1%-113.3%。CP-I和CMPF的内标校正基质效应分别为107.2%和119.3%，90.4%和107.4%。应用经验证的测定法测量10名健康志愿者、14名3-5期CKD患者和14名5D CKD患者的血浆CP-I和CMPF浓度。所有样品中测得的浓度均在校准范围内。我们的新方法在临床上可用于同时测量人体样本中的血浆CP-I和CMPF浓度，并有助于揭示CKD患者中OATB 1B活性与CMPF蓄积的体内关系。(C)2020爱思唯尔B. V.保留所有权利。
In chronic kidney disease (CKD), organic anion transporting polypeptide (OATP)1B activity is reduced by mechanisms involving 3-carboxy-4-methyl-5-propyl-2-furanpropanoic acid (CMPF), a uremic toxin. Coproporphyrin-I (CP-I) is a sensitive and specific endogenous probe for phenotyping OATP1B activity and a potentially useful tool to individualize the dosage of OATP1B substrates. In this study, we developed and validated an assay for simultaneous quantification of CP-I and CMPF in human plasma using ultrahigh performance liquid chromatography with tandem mass spectrometry (UHPLC-MS/MS). The samples were prepared by solid phase extraction, and then subjected to UHPLC-MS/MS quantification. The assay fulfilled the requirements of the US Food and Drug Administration (FDA) guideline for assay validation, with a lower limit of quantification of 0.1 for CP-I and 50 ng/mL for CMPF. Recovery rates from human plasma ranged from 97.3%-109.8% for CP-I, and 94.1%-113.3% for CMPF. Matrix effects corrected by internal standards varied between 107.2 % and 119.3 % for CP-I, and between 90.4 % and 107.4 % for CMPF. The validated assay was applied to measurement of plasma CP-I and CMPF concentrations in 10 healthy volunteers, 14 stage 3-5 CKD patients, and 14 stage 5D CKD patients. The concentrations measured in all samples were within the calibration ranges. Our novel method may be clinically useful for simultaneous measurement of plasma CP-I and CMPF concentrations in human samples, and contribute to reveal the in vivo relationship of OATB1B activity with accumulation of CMPF in CKD patients. (C) 2020 Elsevier B.V. All rights reserved.