title: Personalized monitoring of therapeutic salicylic acid in dried blood spots using a three-layer setup and desorption electrospray ionization mass spectrometry.
abstract: Desorption electrospray ionization (DESI) mass spectrometry is an emerging technology for direct therapeutic drug monitoring in dried blood spots (DBS). Current DBS methods require manual application of small molecules as internal standards for absolute drug quantification. With industrial standardization in mind, we superseded the manual addition of standard and built a three-layer setup for robust quantification of salicylic acid directly from DBS. We combined a dioctyl sodium sulfosuccinate weave facilitating sample spreading with a cellulose layer for addition of isotope-labeled salicylic acid as internal standard and a filter paper for analysis of the standard-containing sample by DESI-MS. Using this setup, we developed a quantification method for salicylic acid from whole blood with a validated linear curve range from 10 to 2000 mg/L, a relative standard deviation (RSD%) ≤14%, and determination coefficients of 0.997. The limit of detection (LOD) was 8 mg/L and the lower limit of quantification (LLOQ) was 10 mg/L. Recovery rates in method verification by LC-MS/MS were 97 to 101% for blinded samples. Most importantly, a study in healthy volunteers after administration of a single dose of Aspirin provides evidence to suggest that the three-layer setup may enable individual pharmacokinetic and endpoint testing following blood collection by finger pricking by patients at home. Taken together, our data suggests that DBS-based quantification of drugs by DESI-MS on pre-manufactured three-layer cartridges may be a promising approach for future near-patient therapeutic drug monitoring.
authors.affiliation: Instrumental Analysis and Bioanalysis, Department of Biotechnology, Mannheim University of Applied Sciences, Paul-Wittsack-Str. 10, 68163, Mannheim, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Siebenhaar
authors.forename: Kai
authors.initials: K
authors.lastname: Küllmer
authors.forename: Nuno Miguel de Barros
authors.initials: NM
authors.lastname: Fernandes
authors.forename: Volker
authors.initials: V
authors.lastname: Hüllen
authors.forename: Carsten
authors.initials: C
authors.lastname: Hopf
mesh_terms: D003890:Desiccation; D016903:Drug Monitoring / Q000379:methods*; D006801:Humans; D015203:Reproducibility of Results; D020156:Salicylic Acid / Q000097:blood*; D012648:Self Care / Q000379:methods*; D012680:Sensitivity and Specificity; D013048:Specimen Handling / Q000379:methods*; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*
chemical_list: D020156:Salicylic Acid