Validation and Application of a Dried Blood Spot Ceftriaxone Assay
MetadataShow full item record
Dried blood spot (DBS) antibiotic assays can facilitate pharmacokinetic/pharmacodynamic (PK/PD) studies in situations where venous blood sampling is logistically and/or ethically problematic. In this study, we aimed to develop, validate, and apply a DBS ceftriaxone assay. A liquid chromatography-tandem mass spectroscopy (LC-MS/MS) DBS ceftriaxone assay was assessed for matrix effects, process efficiency, recovery, variability, and limits of quantification (LOQ) and detection (LOD). The effects of hematocrit, protein binding, red cell partitioning, and chad positioning were evaluated, and thermal stability was assessed. Plasma, DBS, and cell pellet ceftriaxone concentrations in 10 healthy adults were compared, and plasma concentration-time profiles of DBS and plasma ceftriaxone were incorporated into population PK models. The LOQ and LOD for ceftriaxone in DBS were 0.14 mg/liter and 0.05 mg/liter, respectively. Adjusting for hematocrit, red cell partitioning, and relative recovery, DBS-predicted plasma concentrations were comparable to measured plasma concentrations (r > 0.95, P < 0.0001), and Bland-Altman plots showed no significant bias. The final population PK estimates of clearance, volume of distribution, and time above threshold MICs for measured and DBS-predicted plasma concentrations were similar. At 35°C, 21°C, 4°C, −20°C, and −80°C, ceftriaxone retained >95% initial concentrations in DBS for 14 h, 35 h, 30 days, 21 weeks, and >11 months, respectively. The present DBS ceftriaxone assay is robust and can be used as a surrogate for plasma concentrations to provide valid PK and PK/PD data in a variety of clinical situations, including in studies of young children and of those in remote or resource-poor settings.
Showing items related by title, author, creator and subject.
Validation and application of a dried blood spot assay for biofilm-active antibiotics commonly used for treatment of prosthetic implant infectionsKnippenberg, B.; Page-Sharp, Madhu; Salman, S.; Clark, B.; Dyer, J.; Batty, Kevin; Davis, T.; Manning, L. (2016)Dried blood spot (DBS) antibiotic assays can facilitate pharmacokinetic (PK)/pharmacodynamic (PD) studies in situations where venous blood sampling is logistically difficult. We sought to develop, validate, and apply a ...
Penicillin dried blood spot assay for use in patients receiving intramuscular benzathine penicillin G and other penicillin preparations to prevent rheumatic feverPage-Sharp, Madhu; Coward, J.; Moore, Brioni; Salman, S.; Marshall, L.; Davis, T.; Batty, Kevin; Manning, L. (2017)© 2017 American Society for Microbiology. All Rights Reserved. Rheumatic heart disease (RHD) remains an important global health challenge. Administration of benzathine penicillin (BPG) every 3 to 4 weeks is recommended ...
Tanratana, P.; Ellery, Paul; Westmark, P.; Mast, A.; Sheehan, J. (2018)© 2017 American Heart Association, Inc. Objective - Combined oral contraceptives induce a reversible hypercoagulable state with an enhanced risk of venous thromboembolism, but the underlying mechanism(s) remain unclear. ...