title: Volumetric absorptive microsampling (VAMS) as an alternative to conventional dried blood spots in the quantification of miltefosine in dried blood samples.
abstract: Miltefosine is an oral agent against the neglected tropical disease leishmaniasis, which is mostly endemic in resource-poor areas. Dried blood spot (DBS) sampling is an attractive alternative to plasma sampling for pharmacokinetic studies in these remote areas, but introduces additional variability in analyte quantification due to possible blood spot inhomogeneity and variability in blood spot volume and haematocrit values. Volumetric absorptive microsampling (VAMS) potentially overcomes a few of these issues as the VAMS device absorbs a fixed volume that is processed as a whole. We developed and validated an LC-MS/MS method for the quantification of miltefosine with this novel sampling technique with good performance in terms of linearity, selectivity, accuracy (bias within ±10.8%), precision (CV%≤11.9%), recovery, carry-over and matrix effect. VAMS samples were stable for at least one month at room temperature and 37°C. The impact of haematocrit on assay accuracy was reduced compared to conventional DBS sampling, but indicated a declining recovery with increased haematocrit due to haematocrit dependency in recovery from the sampling device. A clinical validation will be required to investigate whether VAMS is an appropriate and cost-effective alternative sampling method to conventional DBS sampling.
authors.affiliation: Department of Pharmacy & Pharmacology, Antoni van Leeuwenhoek Hospital/Slotervaart Hospital, P.O. Box 90440, 1006 BK, Amsterdam, The Netherlands; Division of Pharmacoepidemiology & Clinical Pharmacology, Utrecht Institute for Pharmaceutical Sciences (UIPS), Faculty of Science, Utrecht University, Universiteitsweg 99, 3584 CG Utrecht, The Netherlands. Electronic address: a.kip@nki.nl.
authors.forename: A E
authors.initials: AE
authors.lastname: Kip
authors.affiliation: Department of Pharmacy & Pharmacology, Antoni van Leeuwenhoek Hospital/Slotervaart Hospital, P.O. Box 90440, 1006 BK, Amsterdam, The Netherlands.
authors.forename: K C
authors.initials: KC
authors.lastname: Kiers
authors.affiliation: Department of Pharmacy & Pharmacology, Antoni van Leeuwenhoek Hospital/Slotervaart Hospital, P.O. Box 90440, 1006 BK, Amsterdam, The Netherlands.
authors.forename: H
authors.initials: H
authors.lastname: Rosing
authors.affiliation: Division of Pharmacoepidemiology & Clinical Pharmacology, Utrecht Institute for Pharmaceutical Sciences (UIPS), Faculty of Science, Utrecht University, Universiteitsweg 99, 3584 CG Utrecht, The Netherlands; Department of Clinical Pharmacology, Antoni van Leeuwenhoek Hospital/the Netherlands Cancer institute, P.O. Box 90203, 1006 BE, Amsterdam, The Netherlands.
authors.forename: J H M
authors.initials: JHM
authors.lastname: Schellens
authors.affiliation: Department of Pharmacy & Pharmacology, Antoni van Leeuwenhoek Hospital/Slotervaart Hospital, P.O. Box 90440, 1006 BK, Amsterdam, The Netherlands; Division of Pharmacoepidemiology & Clinical Pharmacology, Utrecht Institute for Pharmaceutical Sciences (UIPS), Faculty of Science, Utrecht University, Universiteitsweg 99, 3584 CG Utrecht, The Netherlands; Department of Clinical Pharmacology, Antoni van Leeuwenhoek Hospital/the Netherlands Cancer institute, P.O. Box 90203, 1006 BE, Amsterdam, The Netherlands.
authors.forename: J H
authors.initials: JH
authors.lastname: Beijnen
authors.affiliation: Division of Pharmacoepidemiology & Clinical Pharmacology, Utrecht Institute for Pharmaceutical Sciences (UIPS), Faculty of Science, Utrecht University, Universiteitsweg 99, 3584 CG Utrecht, The Netherlands; Pharmacometrics Research Group, Department of Pharmaceutical Biosciences, Uppsala University, Box 570, 751 23 Uppsala, Sweden.
authors.forename: T P C
authors.initials: TPC
authors.lastname: Dorlo
mesh_terms: D000981:Antiprotozoal Agents / Q000032:analysis / Q000097:blood*; D002853:Chromatography, Liquid / Q000379:methods; D059788:Dried Blood Spot Testing / Q000379:methods*; D006801:Humans; D010767:Phosphorylcholine / Q000031:analogs & derivatives* / Q000032:analysis / Q000097:blood; D013048:Specimen Handling / Q000379:methods; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D000981:Antiprotozoal Agents; D010767:Phosphorylcholine; C039128:miltefosine
keywords: Bioanalysis; Dried blood; Hematocrit; LC–MS/MS; Miltefosine; Volumetric absorptive microsampling (VAMS)