Validation and Clinical Evaluation of a Novel Method To Measure Miltefosine in Leishmaniasis Patients Using Dried Blood Spot Sample Collection

Antimicrobial Agents and Chemotherapy
A E KipT P C Dorlo

Abstract

To facilitate future pharmacokinetic studies of combination treatments against leishmaniasis in remote regions in which the disease is endemic, a simple cheap sampling method is required for miltefosine quantification. The aims of this study were to validate a liquid chromatography-tandem mass spectrometry method to quantify miltefosine in dried blood spot (DBS) samples and to validate its use with Ethiopian patients with visceral leishmaniasis (VL). Since hematocrit (Ht) levels are typically severely decreased in VL patients, returning to normal during treatment, the method was evaluated over a range of clinically relevant Ht values. Miltefosine was extracted from DBS samples using a simple method of pretreatment with methanol, resulting in >97% recovery. The method was validated over a calibration range of 10 to 2,000 ng/ml, and accuracy and precision were within ±11.2% and ≤7.0% (≤19.1% at the lower limit of quantification), respectively. The method was accurate and precise for blood spot volumes between 10 and 30 μl and for Ht levels of 20 to 35%, although a linear effect of Ht levels on miltefosine quantification was observed in the bioanalytical validation. DBS samples were stable for at least 162 days at 37°C. Clinical v...Continue Reading

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Citations

Jul 9, 2016·Journal of Pharmaceutical and Biomedical Analysis·Yeliz EnderleJürgen Burhenne
Aug 1, 2016·Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences·Guru R ValicherlaJiaur R Gayen
Aug 2, 2017·Clinical Pharmacokinetics·Anke E KipThomas P C Dorlo
Oct 26, 2021·International Journal of Antimicrobial Agents·Semra PalićThomas P C Dorlo

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NCT02011958

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