Alternative matrices for therapeutic drug monitoring of immunosuppressive agents using LC-MS/MS.

Alternative matrices for therapeutic drug monitoring of immunosuppressive agents using LC-MS/MS.
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使用LC-MS/MS对免疫抑制剂进行治疗药物监测的替代矩阵。

DOI:
10.4155/bio.15.35
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发表时间:
2015
期刊:
影响因子:
1.8
通讯作者:
Akhlaghi F
Akhlaghi F
中科院分区:
医学4区
文献类型:
--
作者:
Ghareeb M;Akhlaghi F

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用于实体器官移植的免疫抑制药物通常具有窄的治疗窗和高的受试者内和受试者间变异性。为了确保令人满意的暴露,治疗药物监测(TDM)在任何成功的移植后维持治疗中起着关键作用。目前,最佳免疫抑制剂浓度的建议是基于血液/血浆测量。然而,它们引入了许多缺点,包括对同种异体移植物存活和毒性的预测不佳,与作用部位的药物浓度的弱相关性以及样本收集的侵入性。因此,研究了替代基质。本文综述了串联质谱(LC-MS/MS)方法用于免疫抑制药物的定量利用非常规基质,即口服液,手指采血和细胞内和组织内采样。讨论了此类替代介质的优点、缺点和临床应用。此外,以表格形式提供了关于这些方法的样品提取技术和基本色谱信息。
Immunosuppressive drugs used in solid organ transplants typically have narrow therapeutic windows and high intra- and intersubject variability. To ensure satisfactory exposure, therapeutic drug monitoring (TDM) plays a pivotal role in any successful posttransplant maintenance therapy. Currently, recommendations for optimum immunosuppressant concentrations are based on blood/plasma measurements. However, they introduce many disadvantages, including poor prediction of allograft survival and toxicity, a weak correlation with drug concentrations at the site of action and the invasive nature of the sample collection. Thus, alternative matrices have been investigated. This paper reviews tandem-mass spectrometry (LC–MS/MS) methods used for the quantification of immunosuppressant drugs utilizing nonconventional matrices, namely oral fluids, fingerprick blood and intracellular and intratissue sampling. The advantages, disadvantages and clinical application of such alternative mediums are discussed. Additionally, sample extraction techniques and basic chromatography information regarding these methods are presented in tabulated form.
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