Dried blood spot UHPLC-MS/MS analysis of oseltamivir and oseltamivircarboxylate—a validated assay for the clinic
Open Access
- 3 May 2011
- journal article
- research article
- Published by Springer Science and Business Media LLC in Analytical and Bioanalytical Chemistry
- Vol. 400 (10), 3473-3479
- https://doi.org/10.1007/s00216-011-5050-z
Abstract
The neuraminidase inhibitor oseltamivir (Tamiflu®) is currently the first-line therapy for patients with influenza virus infection. Common analysis of the prodrug and its active metabolite oseltamivircarboxylate is determined via extraction from plasma. Compared with these assays, dried blood spot (DBS) analysis provides several advantages, including a minimum sample volume required for the measurement of drugs in whole blood. Samples can easily be obtained via a simple, non-invasive finger or heel prick. Mainly, these characteristics make DBS an ideal tool for pediatrics and to measure multiple time points such as those needed in therapeutic drug monitoring or pharmacokinetic studies. Additionally, DBS sample preparation, stability, and storage are usually most convenient. In the present work, we developed and fully validated a DBS assay for the simultaneous determination of oseltamivir and oseltamivircarboxylate concentrations in human whole blood. We demonstrate the simplicity of DBS sample preparation, and a fast, accurate and reproducible analysis using ultra high-performance liquid chromatography coupled to a triple quadrupole mass spectrometer. A thorough validation on the basis of the most recent FDA guidelines for bioanalytical method validation showed that the method is selective, precise, and accurate (≤15% RSD), and sensitive over the relevant clinical range of 5–1,500 ng/mL for oseltamivir and 20–1,500 ng/mL for the oseltamivircarboxylate metabolite. As a proof of concept, oseltamivir and oseltamivircarboxylate levels were determined in DBS obtained from healthy volunteers who received a single oral dose of Tamiflu®.Keywords
This publication has 18 references indexed in Scilit:
- Dried Blood Spots, Pharmacokinetic Studies and Better Medicines for ChildrenBioanalysis, 2011
- Determination of Oseltamivir (Tamiflu ® ) and Oseltamivir Carboxylate in Dried Blood Spots Using Offline or Online ExtractionBioanalysis, 2011
- Medication Administration Errors and the Pediatric Population: A Systematic Search of the LiteratureJournal of Pediatric Nursing, 2010
- Antivirals for InfluenzaPediatric Drugs, 2010
- Determination of gamma-hydroxybutyric acid in dried blood spots using a simple GC-MS method with direct “on spot” derivatizationAnalytical and Bioanalytical Chemistry, 2010
- Influenza Hemagglutinin and Neuraminidase Membrane GlycoproteinsJournal of Biological Chemistry, 2010
- DBS Sampling Can be Used to Stabilize Prodrugs in Drug Discovery Rodent Studies without the Addition of Esterase InhibitorsBioanalysis, 2010
- Rapid Degradation of Oseltamivir Phosphate in Clinical Samples by Plasma EsterasesAntimicrobial Agents and Chemotherapy, 2006
- Development of a high-performance liquid chromatographic–mass spectrometric assay for the specific and sensitive quantification of Ro 64-0802, an anti-influenza drug, and its pro-drug, oseltamivir, in human and animal plasma and urineJournal of Chromatography B: Biomedical Sciences and Applications, 2000
- The Pharmacokinetics and Tolerability of the Oral Neuraminidase Inhibitor Oseltamivir (Ro 64–0796/GS4104) in Healthy Adult and Elderly VolunteersThe Journal of Clinical Pharmacology, 2000