Development and Validation of a Liquid Chromatography High-Resolution Mass Spectrometry Method for Blood Desmopressin...

Desmopressin (DDAVP), which indirectly increases Coagulation Factor VIII concentrations in the blood, is a common treatment for bleeding disorders such as von Willebrand disease or hemophilia A. However, DDAVP exhibits significant variability in response due to interindividual differences in pharmacokinetics. Consequently, exploring its pharmacokinetics is of primary importance to better understand the relationship between DDAVP administration and therapeutic outcomes. To that end, the measurement of DDAVP concentration is essential. This article describes the development and validation of a liquid chromatography method coupled with high-resolution mass spectrometry detection for quantifying DDAVP in human plasma. After sample pretreatment involving protein precipitation followed by solid-phase extraction, quantification was based on the four most intense isotopes, utilizing targeted single ion monitoring, with a method range of 20-2000 pg.mL^-1. For the four QC levels, accuracy and precision for both inter- and intra-assay measurements were below 11.6% and 13.8%, respectively, meeting FDA recommendations. After validation, this method was applied to a cohort of 10 patients with a deficiency in Coagulation Factor VIII, who received 0.3 μg.kg^-1 of desmopressin acetate. The mean volume of distribution at steady state was 18.8 L (CV% 26.7), the mean clearance was 7.8 L.h^-1 (CV% 25.1), and the mean half-life was 1.8 h (CV% 14.7). Offering valuable insights into the pharmacokinetics of DDAVP, this method will be useful for further studies and holds promise for optimizing treatment regimens in this patient population.