In recent years, off-label use of sirolimus (SIR) has been gaining attention in the clinical practice. However, since it is critical to achieve and maintain therapeutic blood levels of SIR during treatment, the regular monitoring of this drug in individual patients must be implemented, especially in off-label indications of this drug. In this article, a fast, simple, and reliable analytical method for determining SIR levels in whole blood samples is proposed. Sample preparation based on dispersive liquid-liquid microextraction (DLLME) followed by liquid chromatography-mass spectrometry (LC-MS/MS) was fully optimized toward the analysis of SIR and proposed as a fast, simple, and reliable analytical method for determining the pharmacokinetic profile of SIR in whole-blood samples. In addition, the practical applicability of the proposed DLLME-LC-MS/MS method was evaluated by analyzing the pharmacokinetic profile of SIR in whole blood samples obtained from two pediatric patients suffering from lymphatic anomalies, receiving this drug as off-label clinical indication. The proposed methodology can be successfully applied in routine clinical practice for the fast and precise assessment of SIR levels in biological samples, thus allowing SIR dosages to be adjusted in real time during pharmacotherapy. Moreover, the measured SIR levels in the patients indicate the need for monitoring between doses to ensure the optimal pharmacotherapy of patients.
Keywords: DLLME; LC-MS/MS; SIR; therapeutic drug monitoring; whole blood samples.
© 2023 the author(s), published by De Gruyter.