Development and validation of an ultra-performance liquid chromatography-tandem mass spectrometry method for the quantification of the antimalarial drug pyronaridine in human whole blood.

Autor: Schouten WM; Department of Pharmacy & Pharmacology, Antoni van Leeuwenhoek/The Netherlands Cancer Institute, Amsterdam, the Netherlands., Roseboom IC; Department of Pharmacy & Pharmacology, Antoni van Leeuwenhoek/The Netherlands Cancer Institute, Amsterdam, the Netherlands., Lucas L; Department of Pharmacy & Pharmacology, Antoni van Leeuwenhoek/The Netherlands Cancer Institute, Amsterdam, the Netherlands., Kabalu Tshiongo J; Department of Tropical Medicine University of Kinshasa (UNIKIN), Kinshasa, Congo; Amsterdam University Medical Centres, Department of Medical Microbiology and Infection Prevention, Laboratory for Experimental Parasitology, Academic Medical Centres at the University of Amsterdam, Amsterdam, the Netherlands; Amsterdam Institute for Infection and Immunity, Infectious Diseases Programme, Amsterdam, the Netherlands., Muhindo Mavoko H; Department of Tropical Medicine University of Kinshasa (UNIKIN), Kinshasa, Congo., Kayentao K; Malaria Research and Training Center (MRTC), University of Sciences, Techniques and Technologies of Bamako (USTTB), Bamako, Mali., Rosing H; Department of Pharmacy & Pharmacology, Antoni van Leeuwenhoek/The Netherlands Cancer Institute, Amsterdam, the Netherlands., Huitema ADR; Department of Pharmacy & Pharmacology, Antoni van Leeuwenhoek/The Netherlands Cancer Institute, Amsterdam, the Netherlands; Department of Pharmacology, Princess Maxima Center, Utrecht, the Netherlands; Department of Clinical Pharmacy, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands., Beijnen JH; Department of Pharmacy & Pharmacology, Antoni van Leeuwenhoek/The Netherlands Cancer Institute, Amsterdam, the Netherlands; Utrecht Institute of Pharmaceutical Sciences, Utrecht University, Utrecht, the Netherlands., Dorlo TPC; Department of Pharmacy & Pharmacology, Antoni van Leeuwenhoek/The Netherlands Cancer Institute, Amsterdam, the Netherlands; Department of Pharmacy Uppsala University, Uppsala, Sweden. Electronic address: thomas.dorlo@farmaci.uu.se.
Jazyk: angličtina
Zdroj: Journal of pharmaceutical and biomedical analysis [J Pharm Biomed Anal] 2024 Aug 01; Vol. 245, pp. 116154. Date of Electronic Publication: 2024 Apr 16.
DOI: 10.1016/j.jpba.2024.116154
Abstrakt: Malaria remains a major health concern, aggravated by emerging resistance of the parasite to existing treatments. The World Health Organization recently endorsed the use of artesunate-pyronaridine to treat uncomplicated malaria. However, there is a lack of clinical pharmacokinetic (PK) data of pyronaridine, particularly in special populations such as children and pregnant women. Existing methods for the quantification of pyronaridine in biological matrices to support PK studies exhibit several drawbacks. These include limited sensitivity, a large sample volume required, and extensive analysis time. To overcome these limitations, an ultra-performance reversed-phase liquid chromatography tandem-mass spectrometry method to determine pyronaridine was developed and validated according to international guidelines. The method enabled fast and accurate quantification of pyronaridine in whole blood across a clinically relevant concentration range of 0.500-500 ng/mL (r 2 ≥ 0.9963), with a required sample volume of 50 µL. Pyronaridine was extracted from whole blood using liquid-liquid extraction, effectively eliminating the matrix effect and preventing ion enhancement or suppression. The method achieved a satisfactory reproducible sample preparation recovery of 77%, accuracy (as bias) and precision were within ±8.2% and ≤5.3%, respectively. Stability experiments demonstrated that pyronaridine was stable for up to 315 days when stored at -70°C. Adjustments to the chromatographic system substantially reduced carry-over and improved sensitivity compared to prior methods. The method was successfully applied to quantify pyronaridine in whole blood samples from a selection of pregnant malaria patients participating in the PYRAPREG clinical trial (PACTR202011812241529) in the Democratic Republic of the Congo, demonstrating its suitability to support future PK studies. Furthermore, the enhanced sensitivity allows for the determination of pyronaridine up to 42 days post-treatment initiation, enabling assessment of the terminal elimination half-life.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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