用于测量类固醇难治性移植物抗宿主病中鲁索利替尼的液相色谱-串联质谱法的开发与临床验证:迈向优化治疗的第一步。

IF 2.3 3区 医学 Q2 HEMATOLOGY
Sara Redondo, María Costa, Maria-Estela Moreno-Martinez, Miguel Arguello-Tomas, Mireia Riba, Olga Aso, Eva Iranzo, Albert Esquirol, Jorge Sierra, Javier Briones, Rodrigo Martino, Edgar Zapico, Irene García-Cadenas
{"title":"用于测量类固醇难治性移植物抗宿主病中鲁索利替尼的液相色谱-串联质谱法的开发与临床验证:迈向优化治疗的第一步。","authors":"Sara Redondo, María Costa, Maria-Estela Moreno-Martinez, Miguel Arguello-Tomas, Mireia Riba, Olga Aso, Eva Iranzo, Albert Esquirol, Jorge Sierra, Javier Briones, Rodrigo Martino, Edgar Zapico, Irene García-Cadenas","doi":"10.1111/ejh.14349","DOIUrl":null,"url":null,"abstract":"<p><strong>Objective: </strong>This non-interventional, prospective, single-center study aimed to develop a technique to measure ruxolitinib (RUX) concentrations and provide preliminary data on the distribution of plasma drug levels in patients with steroid refractory (SR) GvHD.</p><p><strong>Methods: </strong>Between April 2023 and May 2024, we analyzed 48 blood samples from 29 patients with SR-GvHD.</p><p><strong>Results: </strong>Median individual plasma concentrations varied across different RUX doses and largely overlapped: 39.2 ng/mL at 10 mg b.i.d (range: 0-73), 13.1 ng/mL at 10-5 mg (range, 6.1-35.6), and 31.6 ng/mL at 5 mg b.i.d (range: 0.7-99.9). Samples taken under non-optimal temperature conditions showed a lower median concentration of 0.77 ng/mL (range: 0-7.4 ng/mL). The four patients who did not respond at days +28 and +180 after RUX initiation (3 with lower gastrointestinal aGvHD, and 1 with ocular, hepatic, and pulmonary cGvHD) showed a median concentration of only (7.4 ng/mL (range, 0-29) ng/mL) with full dosing.</p><p><strong>Conclusions: </strong>The introduction and validation of a liquid chromatography-tandem mass spectrometry method for quantifying plasma RUX concentrations was feasible in our center. Administering predetermined and fixed doses of RUX in patients with SR-GvHD showed highly variable and overlapping plasma drug concentrations. This underscores the potential importance of RUX- pharmacokinetics (PK) monitoring.</p>","PeriodicalId":11955,"journal":{"name":"European Journal of Haematology","volume":" ","pages":""},"PeriodicalIF":2.3000,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Development and Clinical Validation of Liquid Chromatography-Tandem Mass Spectrometry for Measuring Ruxolitinib in Steroid-Refractory Graft-Versus-Host Disease: A First Step Towards Optimized Treatment.\",\"authors\":\"Sara Redondo, María Costa, Maria-Estela Moreno-Martinez, Miguel Arguello-Tomas, Mireia Riba, Olga Aso, Eva Iranzo, Albert Esquirol, Jorge Sierra, Javier Briones, Rodrigo Martino, Edgar Zapico, Irene García-Cadenas\",\"doi\":\"10.1111/ejh.14349\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Objective: </strong>This non-interventional, prospective, single-center study aimed to develop a technique to measure ruxolitinib (RUX) concentrations and provide preliminary data on the distribution of plasma drug levels in patients with steroid refractory (SR) GvHD.</p><p><strong>Methods: </strong>Between April 2023 and May 2024, we analyzed 48 blood samples from 29 patients with SR-GvHD.</p><p><strong>Results: </strong>Median individual plasma concentrations varied across different RUX doses and largely overlapped: 39.2 ng/mL at 10 mg b.i.d (range: 0-73), 13.1 ng/mL at 10-5 mg (range, 6.1-35.6), and 31.6 ng/mL at 5 mg b.i.d (range: 0.7-99.9). Samples taken under non-optimal temperature conditions showed a lower median concentration of 0.77 ng/mL (range: 0-7.4 ng/mL). The four patients who did not respond at days +28 and +180 after RUX initiation (3 with lower gastrointestinal aGvHD, and 1 with ocular, hepatic, and pulmonary cGvHD) showed a median concentration of only (7.4 ng/mL (range, 0-29) ng/mL) with full dosing.</p><p><strong>Conclusions: </strong>The introduction and validation of a liquid chromatography-tandem mass spectrometry method for quantifying plasma RUX concentrations was feasible in our center. Administering predetermined and fixed doses of RUX in patients with SR-GvHD showed highly variable and overlapping plasma drug concentrations. This underscores the potential importance of RUX- pharmacokinetics (PK) monitoring.</p>\",\"PeriodicalId\":11955,\"journal\":{\"name\":\"European Journal of Haematology\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":2.3000,\"publicationDate\":\"2024-11-15\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"European Journal of Haematology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1111/ejh.14349\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"HEMATOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"European Journal of Haematology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1111/ejh.14349","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"HEMATOLOGY","Score":null,"Total":0}
引用次数: 0

摘要

研究目的这项非干预性、前瞻性、单中心研究旨在开发一种测量鲁索利替尼(RUX)浓度的技术,并提供类固醇难治性(SR)GvHD患者血浆药物水平分布的初步数据:2023年4月至2024年5月,我们分析了29名SR-GvHD患者的48份血液样本:不同 RUX 剂量的单个血浆浓度中位数各不相同,且基本重叠:10 毫克每天服用时为 39.2 纳克/毫升(范围:0-73),10-5 毫克时为 13.1 纳克/毫升(范围:6.1-35.6),5 毫克每天服用时为 31.6 纳克/毫升(范围:0.7-99.9)。在非最佳温度条件下采集的样本显示的中位浓度较低,为 0.77 纳克/毫升(范围:0-7.4 纳克/毫升)。在开始使用 RUX 后的第 +28 天和第 +180天,4 名无反应的患者(3 名患有下胃肠道 aGvHD,1 名患有眼、肝和肺 cGvHD)在完全给药的情况下,中位浓度仅为(7.4 ng/mL(范围:0-29)ng/mL):结论:在本中心采用液相色谱-串联质谱法对血浆 RUX 浓度进行定量分析并进行验证是可行的。给SR-GvHD患者注射预定剂量和固定剂量的RUX,结果显示血浆药物浓度变化很大,且存在重叠。这凸显了RUX药代动力学(PK)监测的潜在重要性。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Development and Clinical Validation of Liquid Chromatography-Tandem Mass Spectrometry for Measuring Ruxolitinib in Steroid-Refractory Graft-Versus-Host Disease: A First Step Towards Optimized Treatment.

Objective: This non-interventional, prospective, single-center study aimed to develop a technique to measure ruxolitinib (RUX) concentrations and provide preliminary data on the distribution of plasma drug levels in patients with steroid refractory (SR) GvHD.

Methods: Between April 2023 and May 2024, we analyzed 48 blood samples from 29 patients with SR-GvHD.

Results: Median individual plasma concentrations varied across different RUX doses and largely overlapped: 39.2 ng/mL at 10 mg b.i.d (range: 0-73), 13.1 ng/mL at 10-5 mg (range, 6.1-35.6), and 31.6 ng/mL at 5 mg b.i.d (range: 0.7-99.9). Samples taken under non-optimal temperature conditions showed a lower median concentration of 0.77 ng/mL (range: 0-7.4 ng/mL). The four patients who did not respond at days +28 and +180 after RUX initiation (3 with lower gastrointestinal aGvHD, and 1 with ocular, hepatic, and pulmonary cGvHD) showed a median concentration of only (7.4 ng/mL (range, 0-29) ng/mL) with full dosing.

Conclusions: The introduction and validation of a liquid chromatography-tandem mass spectrometry method for quantifying plasma RUX concentrations was feasible in our center. Administering predetermined and fixed doses of RUX in patients with SR-GvHD showed highly variable and overlapping plasma drug concentrations. This underscores the potential importance of RUX- pharmacokinetics (PK) monitoring.

求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
CiteScore
5.50
自引率
0.00%
发文量
168
审稿时长
4-8 weeks
期刊介绍: European Journal of Haematology is an international journal for communication of basic and clinical research in haematology. The journal welcomes manuscripts on molecular, cellular and clinical research on diseases of the blood, vascular and lymphatic tissue, and on basic molecular and cellular research related to normal development and function of the blood, vascular and lymphatic tissue. The journal also welcomes reviews on clinical haematology and basic research, case reports, and clinical pictures.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信