Synthesis of [2H]- and [13C]-labeled pyronaridine tetraphosphate-an antimalarial drug

• Published in: Journal of labelled compounds & radiopharmaceuticals 2009-02, Vol.52 (2), p.56-62
• Main Authors: Park, Sang Hyun, Jeong, Yeon Jun, Pradeep, Kannampalli
• Format: Article
• Language: English
• Subjects: antimalarial drug; Biological and medical sciences; carbon-13; Contrast media. Radiopharmaceuticals; deuterium; Medical sciences; microwave irradiation technique; Pharmacology. Drug treatments; Plasmodium falciparum; pyronaridine tetraphosphate
• ISSN: 0362-4803; 1099-1344
• DOI: 10.1002/jlcr.1568

The increasing prevalence of strains of Plasmodium falciparum resistant to chloroquine and other antimalarial drugs, necessitates the need for developing novel antimalarial drugs with a potent pharmacological activity. Pyronaridine tetraphosphate (PNDP) is one such drug that is currently undergoing preclinical and clinical trials for use in a chemotherapy treatment of malaria. The present investigation was carried out with the objective of synthesizing carbon‐13 [13C]‐ and deuterium [2H]‐labeled PNDP for use in studying the ADME and pharmacokinetics of the drug. Here, we present a methodology to synthesize [13C]‐ and [2H]‐PNDP using a microwave irradiation technique as this method was found to be more advantageous than the classical method. The labeled compounds thus synthesized had a chemical purity of >99% as determined by HPLC and were also found to be relatively stable up to 3 months when stored under standard conditions. Further they also revealed satisfactory instrumental analysis data. Copyright © 2008 John Wiley & Sons, Ltd. In this investigation, we present a methodology to synthesize [13C]‐ and [2H]‐PNDP using a microwave irradiation technique for use in studying the ADME and pharmacokinetics of the drug. Copyright © 2008 John Wiley & Sons, Ltd.