Development and application of an LC-MS/MS method for 8 antiepileptic drugs and 2 metabolites using microsampling techniques (DBS and VAMS).

IF 2.6 3区 医学 Q3 CHEMISTRY, ANALYTICAL
María Cobo-Golpe, Lucía Paniagua-González, Elena Lendoiro, Miriam Blanco-Ces, Ángela López-Rabuñal, Javier Abella, Dolores Castro, Cristina Melcón, Patricia Fuentes, Iria Carballeira, Carlos García, Carmen Gómez, Manuel López-Rivadulla Lamas, Angelines Cruz, Ana de-Castro-Ríos
{"title":"Development and application of an LC-MS/MS method for 8 antiepileptic drugs and 2 metabolites using microsampling techniques (DBS and VAMS).","authors":"María Cobo-Golpe, Lucía Paniagua-González, Elena Lendoiro, Miriam Blanco-Ces, Ángela López-Rabuñal, Javier Abella, Dolores Castro, Cristina Melcón, Patricia Fuentes, Iria Carballeira, Carlos García, Carmen Gómez, Manuel López-Rivadulla Lamas, Angelines Cruz, Ana de-Castro-Ríos","doi":"10.1093/jat/bkaf073","DOIUrl":null,"url":null,"abstract":"<p><p>Therapeutic drug monitoring (TDM) of antiepileptic drugs (AEDs) is used for optimization and individualization of patients' treatment. Capillary microsampling techniques are a promising alternative to conventional venous sampling for TDM. Both dried blood spots (DBS) and volumetric adsorptive microsampling (VAMS) devices are less invasive and patient-friendly sampling techniques which have been gaining interest in the last years. This study describes the development and validation of an LC-MS/MS method for the determination of 8 AEDs (Carbamazepine, Lacosamide, Levetiracetam, Lamotrigine, Phenobarbital, Valproic acid) and 2 metabolites (10,11-Dihydro-10-hydroxy-carbamazepine (DHCB) and carbamazepine-10,11-epoxide) in DBS and VAMS samples. The method was fully validated for linearity, selectivity, accuracy, precision, carryover, matrix effect, recovery and stability (15 days at room temperature and 72 h in autosampler). Moreover, the volume effect, volcano effect, and the hematocrit (Hct) effect were also assessed for DBS samples. All parameters showed satisfactory results, with a limit of quantification ranging from 0,5 to 10 µg/mL, depending on the analyte. Some instability issues were detected in DBS samples for oxcarbazepine. However, the inclusion of oxcarbazepine's metabolite DHCB overcomes this problem as it was stable under both conditions tested. Moreover, this is the first DBS or VAMS method reporting the inclusion of DHCB, which seems essential for the TDM of oxcarbazepine. The method was applied to 80 paired samples from patients under treatment with these drugs in order to study the suitability of the method for the detection of these compounds, and compare concentrations in paired VAMS, DBS, whole blood and plasma samples. Ratios between paired samples show a promising correlation between microsampling techniques and plasma concentrations.</p>","PeriodicalId":14905,"journal":{"name":"Journal of analytical toxicology","volume":" ","pages":""},"PeriodicalIF":2.6000,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of analytical toxicology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1093/jat/bkaf073","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"CHEMISTRY, ANALYTICAL","Score":null,"Total":0}
引用次数: 0

Abstract

Therapeutic drug monitoring (TDM) of antiepileptic drugs (AEDs) is used for optimization and individualization of patients' treatment. Capillary microsampling techniques are a promising alternative to conventional venous sampling for TDM. Both dried blood spots (DBS) and volumetric adsorptive microsampling (VAMS) devices are less invasive and patient-friendly sampling techniques which have been gaining interest in the last years. This study describes the development and validation of an LC-MS/MS method for the determination of 8 AEDs (Carbamazepine, Lacosamide, Levetiracetam, Lamotrigine, Phenobarbital, Valproic acid) and 2 metabolites (10,11-Dihydro-10-hydroxy-carbamazepine (DHCB) and carbamazepine-10,11-epoxide) in DBS and VAMS samples. The method was fully validated for linearity, selectivity, accuracy, precision, carryover, matrix effect, recovery and stability (15 days at room temperature and 72 h in autosampler). Moreover, the volume effect, volcano effect, and the hematocrit (Hct) effect were also assessed for DBS samples. All parameters showed satisfactory results, with a limit of quantification ranging from 0,5 to 10 µg/mL, depending on the analyte. Some instability issues were detected in DBS samples for oxcarbazepine. However, the inclusion of oxcarbazepine's metabolite DHCB overcomes this problem as it was stable under both conditions tested. Moreover, this is the first DBS or VAMS method reporting the inclusion of DHCB, which seems essential for the TDM of oxcarbazepine. The method was applied to 80 paired samples from patients under treatment with these drugs in order to study the suitability of the method for the detection of these compounds, and compare concentrations in paired VAMS, DBS, whole blood and plasma samples. Ratios between paired samples show a promising correlation between microsampling techniques and plasma concentrations.

采用微进样技术(DBS和VAMS)建立8种抗癫痫药物和2种代谢物的LC-MS/MS方法及应用。
抗癫痫药物(aed)的治疗药物监测(TDM)用于优化和个性化患者的治疗。毛细管显微取样技术是一种有前途的替代传统静脉取样TDM。干血点(DBS)和体积吸附微采样(VAMS)设备都是侵入性较小且对患者友好的采样技术,近年来受到越来越多的关注。本研究建立并验证了LC-MS/MS法测定DBS和VAMS样品中8种AEDs(卡马西平、拉科沙胺、左乙拉西坦、拉莫三嗪、苯巴比妥、丙戊酸)和2种代谢物(10,11-二氢-10-羟基卡马西平(DHCB)和卡马西平-10,11-环氧化物)。对该方法进行了线性、选择性、准确度、精密度、结转、基质效应、回收率和稳定性(室温下15天,自动进样器中72 h)的充分验证。此外,还评估了DBS样品的体积效应、火山效应和红细胞压积(Hct)效应。所有参数均显示令人满意的结果,定量限范围为0.5至10µg/mL,具体取决于分析物。在奥卡西平的DBS样品中检测到一些不稳定性问题。然而,奥卡西平的代谢物DHCB的加入克服了这个问题,因为它在两种测试条件下都是稳定的。此外,这是DBS或VAMS方法首次报道了DHCB的纳入,DHCB似乎对奥卡西平的TDM至关重要。将该方法应用于80例正在接受这些药物治疗的患者的配对样本,以研究该方法检测这些化合物的适用性,并比较配对VAMS、DBS、全血和血浆样本中的浓度。配对样品之间的比率显示了微采样技术与血浆浓度之间有希望的相关性。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 求助全文
来源期刊
CiteScore
5.10
自引率
20.00%
发文量
92
审稿时长
6-12 weeks
期刊介绍: The Journal of Analytical Toxicology (JAT) is an international toxicology journal devoted to the timely dissemination of scientific communications concerning potentially toxic substances and drug identification, isolation, and quantitation. Since its inception in 1977, the Journal of Analytical Toxicology has striven to present state-of-the-art techniques used in toxicology labs. The peer-review process provided by the distinguished members of the Editorial Advisory Board ensures the high-quality and integrity of articles published in the Journal of Analytical Toxicology. Timely presentation of the latest toxicology developments is ensured through Technical Notes, Case Reports, and Letters to the Editor.
×
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:604180095
Book学术官方微信