The comparison of two volumetric microsampling devices (qDBS and VAMS) for determining ganciclovir levels in capillary blood using the LC-MS/MS technique in pediatric renal transplant recipients.

(Val)Ganciclovir (VGCV) is utilised for the prevention and treatment of cytomegalovirus (CMV) infections in pediatric patients who have undergone renal transplants. Due to toxic side effects, therapeutic drug monitoring (TDM) is recommended, especially in vulnerable populations. Microsampling offers collecting small volumes of body fluids (<50 µL), making it ideal for TDM service. This study aimed to develop and clinically validate two microsampling techniques - Mitra™ and Capitainer®- employing volumetric absorptive microsampling (VAMS) and quantitative dried blood spot (qDBS) methods, respectively. Additionally, reference methods for analysing GCV in whole blood and plasma were validated. The LC-MS/MS multi-matrix method for quantifying GCV was validated using a calibration range of 0.01-25 mg/L in accordance with ICH M10 and Food and Drug Administration guidelines. The calculated accuracies and precisions for all tested matrices were within 15 %. No significant matrix and carryover effects were observed. Clinical validation demonstrated the efficacy of the examined microsampling devices in practice, highlighting the feasibility of home-based self-sampling. The developed methodologies were utilised to assess GCV levels in clinical samples from pediatric renal transplant recipients receiving VGCV treatment within a preemptive or prophylactic CMV protocol. The results were clinically evaluated through regression and bias estimation analyses, confirming a high level of correlation between GCV levels in the tested matrices. In conclusion, the newly developed, straightforward, and robust multi-matrix LC-MS/MS method has been effectively validated and integrated into clinical practice. For the first time in the literature, we demonstrated the analytical and clinical feasibility of tested microsampling devices for routine GCV concentration monitoring.