Change search
ReferencesLink to record
Permanent link

Direct link
Validation and clinical evaluation of a novel method to measure miltefosine in leishmaniasis patients using dried blood spot sample collection
Show others and affiliations
2016 (English)In: Antimicrobial Agents and Chemotherapy, ISSN 0066-4804, E-ISSN 1098-6596, Vol. 60, no 4, 2081-2089 p.Article in journal (Refereed) Published
Abstract [en]

To facilitate future pharmacokinetic studies of combination treatments against leishmaniasis in remote endemic regions, a simple and cheap sampling methodology was required for miltefosine quantification. The aim of this study was to validate a liquid chromatography-tandem mass spectrometry method to quantify miltefosine in dried blood spots (DBS) and to validate its use in Ethiopian visceral leishmaniasis (VL) patients. Since hematocrit (Ht) values are typically severely decreased in VL patients, regressing to normal during treatment, the method was evaluated over a range of clinically relevant Ht values.Miltefosine was extracted from DBS using a simple pre-treatment method with methanol, resulting in >97% recovery. The method was validated over a calibration range of 10-2,000 ng/mL and accuracy and precision were within ±11.2% and ≤7.0% (≤19.1% at LLOQ), respectively. The method was accurate and precise for blood spot volumes between 10-30 μL and for an Ht of 20-35%, though a linear effect of Ht on miltefosine quantification was observed in the bioanalytical validation. DBS samples were stable for at least 162 days at 37°C.Clinical validation of the method using paired DBS and plasma samples from 16 VL patients showed a median observed DBS:plasma miltefosine concentration ratio of 0.99, with good correlation (Pearson's r=0.946). Correcting for patient-specific Ht did not further improve the concordance between the sampling methods.This successfully validated method to quantify miltefosine in DBS was demonstrated to be a valid and practical alternative to venous blood sampling which can be applied in future miltefosine pharmacokinetic studies in leishmaniasis patients, without Ht-correction.

Place, publisher, year, edition, pages
2016. Vol. 60, no 4, 2081-2089 p.
National Category
Pharmacology and Toxicology
URN: urn:nbn:se:uu:diva-279067DOI: 10.1128/AAC.02976-15ISI: 000376496100016PubMedID: 26787691OAI: diva2:907501
EU, FP7, Seventh Framework Programme
Available from: 2016-02-29 Created: 2016-02-29 Last updated: 2016-08-29Bibliographically approved

Open Access in DiVA

fulltext(885 kB)7 downloads
File information
File name FULLTEXT01.pdfFile size 885 kBChecksum SHA-512
Type fulltextMimetype application/pdf

Other links

Publisher's full textPubMed

Search in DiVA

By author/editor
Dorlo, Thomas P. C.
By organisation
Department of Pharmaceutical Biosciences
In the same journal
Antimicrobial Agents and Chemotherapy
Pharmacology and Toxicology

Search outside of DiVA

GoogleGoogle Scholar
Total: 7 downloads
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

Altmetric score

Total: 55 hits
ReferencesLink to record
Permanent link

Direct link