Ghareeb Mwlod, Akhlaghi Fatemeh
Clinical Pharmacokinetics Research Laboratory, Department of Biomedical & Pharmaceutical Sciences, 495A College of Pharmacy, University of Rhode Island, 7 Greenhouse Road, Kingston, RI 02881, USA.
Bioanalysis. 2015;7(8):1037-58. doi: 10.4155/bio.15.35.
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.
实体器官移植中使用的免疫抑制药物通常治疗窗狭窄，个体内和个体间差异大。为确保达到满意的药物暴露水平，治疗药物监测（TDM）在任何成功的移植后维持治疗中都起着关键作用。目前，关于最佳免疫抑制剂浓度的建议基于血液/血浆测量。然而，它们存在许多缺点，包括对同种异体移植物存活和毒性的预测不佳、与作用部位药物浓度的相关性较弱以及样本采集的侵入性。因此，人们对替代基质进行了研究。本文综述了用于定量免疫抑制药物的串联质谱（LC-MS/MS）方法，这些方法利用非常规基质，即口腔液、指尖血以及细胞内和组织内采样。讨论了此类替代介质的优缺点和临床应用。此外，还以表格形式列出了这些方法的样本提取技术和基本色谱信息。
