Department of Drug Chemistry, Pharmaceutical and Biomedical Analysis, Faculty of Pharmacy, Medical University of Warsaw, 02-097 Warsaw, Poland; Therapeutic Drug Monitoring, Clinical Pharmacokinetics and Toxicology Laboratory Unit, Department of Clinical Biochemistry, The Children's Memorial Health Institute, 04-730 Warsaw, Poland.
Student's Scientific Association in the Department of Drug Chemistry, Pharmaceutical and Biomedical Analysis, Faculty of Pharmacy, Medical University of Warsaw, 02-097 Warsaw, Poland.
Clin Chim Acta. 2024 Aug 15;562:119877. doi: 10.1016/j.cca.2024.119877. Epub 2024 Jul 16.
Ciclosporin (CSA) is an immunosuppressive agent that requires therapeutic drug monitoring (TDM). High partitioning in erythrocytes indicates that whole blood (WB) is a suitable matrix for CSA determination. Alternative sampling strategies, such as volumetric absorptive microsampling (VAMS), are novel possibilities for blood collection during TDM for various analytes, including immunosuppressants. This technique is attractive for vulnerable pediatric patients, including home-based self-sampling, remote therapy, and adherence control.
This study aimed to develop and validate a new method for CSA determination based on liquid chromatography-tandem mass spectrometry (LC-MS/MS) of WB and VAMS samples. Additionally, these methods were applied for CSA determination in clinical samples from pediatric transplant recipients. A strong point of this study is the assessment of an external proficiency testing scheme.
Both methods were successfully validated within the 1-2000 ng/mL calibration range, with LOD 0.5 and 1 ng/mL for WB and VAMS methods, respectively. All the validation parameters fulfilled the international acceptance criteria for bioanalytical methods. Cross-validation confirmed the interchangeability of the LC-MS/MS method developed in this study.
This study developed and validated novel methods for CSA determination in whole blood and VAMS using LC-MS/MS. Clinical validation and proficiency testing confirmed their utility in routine clinical practice.
环孢素（CSA）是一种免疫抑制剂，需要进行治疗药物监测（TDM）。红细胞中的高分配表明全血（WB）是 CSA 测定的合适基质。替代采样策略，如体积吸收微采样（VAMS），是 TDM 中用于各种分析物（包括免疫抑制剂）采血的新可能性。这项技术对于脆弱的儿科患者具有吸引力，包括家庭自我采样、远程治疗和依从性控制。
本研究旨在开发和验证一种基于液相色谱-串联质谱（LC-MS/MS）的 WB 和 VAMS 样本中 CSA 测定的新方法。此外，这些方法还应用于儿科移植受者的临床样本中的 CSA 测定。本研究的一个优点是评估外部能力验证计划。
两种方法均在 1-2000ng/mL 的校准范围内成功验证，WB 和 VAMS 方法的检测限分别为 0.5 和 1ng/mL。所有验证参数均满足生物分析方法的国际接受标准。交叉验证证实了本研究中开发的 LC-MS/MS 方法的可互换性。
本研究开发并验证了 LC-MS/MS 用于全血和 VAMS 中 CSA 测定的新方法。临床验证和能力验证证实了它们在常规临床实践中的实用性。
