Quantification of the antimalarial drug pyronaridine in whole blood using LC–MS/MS — Increased sensitivity resulting from reduced non-specific binding

Blessborn, Daniel; Kaewkhao, Karnrawee; Song, Lijiang; White, Nicholas J.; Day, Nicholas P. J.; Tärning, Joel

doi:10.1016/j.jpba.2017.08.023

Cited by 8 publications

(3 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Pyronaridine has been shown to have an extended half-life in humans, with a half-life elimination in whole blood of approximately 17 d [84] and 33.5 d for the total radioactive half-life [85] which compares favorably with our observations in mice in this study (Fig 3). A mass balance study in healthy volunteers indicated nine primary and four secondary metabolites of pyronaridine [85] and recombinant CYP studies suggested that these metabolites were generated by cytochrome P450s CYP1A2, CYP2D6, and CYP3A4 [31].…”

Section: Discussionsupporting

confidence: 87%

Repurposing the antimalarial pyronaridine tetraphosphate to protect against Ebola virus infection

et al. 2019

View full text Add to dashboard Cite

Recent outbreaks of the Ebola virus (EBOV) have focused attention on the dire need for antivirals to treat these patients. We identified pyronaridine tetraphosphate as a potential candidate as it is an approved drug in the European Union which is currently used in combination with artesunate as a treatment for malaria (EC50 between 420 nM—1.14 μM against EBOV in HeLa cells). Range-finding studies in mice directed us to a single 75 mg/kg i.p. dose 1 hr after infection which resulted in 100% survival and statistically significantly reduced viremia at study day 3 from a lethal challenge with mouse-adapted EBOV (maEBOV). Further, an EBOV window study suggested we could dose pyronaridine 2 or 24 hrs post-exposure to result in similar efficacy. Analysis of cytokine and chemokine panels suggests that pyronaridine may act as an immunomodulator during an EBOV infection. Our studies with pyronaridine clearly demonstrate potential utility for its repurposing as an antiviral against EBOV and merits further study in larger animal models with the added benefit of already being used as a treatment against malaria.

show abstract

Section: Discussionsupporting

confidence: 87%

Repurposing the antimalarial pyronaridine tetraphosphate to protect against Ebola virus infection

et al. 2019

View full text Add to dashboard Cite

show abstract

“…Besides, SPE has the best clean-up efficiency but is time consuming, which often serves as the last option when both PPT and LLE fell flat (Blessborn et al, 2017;Koller, Zubiaur, Saiz-Rodriguez, Abad-Santos, & Wojnicz, 2019;Montesano et al, 2017). Occasionally, researchers may choose to combine two of these methods.…”

Section: Conventional Pretreatment Methodsmentioning

confidence: 99%

Technologies to improve the sensitivity of existing chromatographic methods used for bioanalytical studies

Chen

Gao

Zhong

2020

Biomedical Chromatography

View full text Add to dashboard Cite

Chromatographic method has long been recognized as the most widely used separation method in bioanalytical research. However, the relatively low sensitivity of existing chromatographic methods remains a significant challenge, as the requirements for experimental procedures become more demanding. This review discusses the main causes for the low sensitivity of chromatographic methods and aims to introduce different technologies for enhancing their sensitivity in the following aspects: (i) different pretreatment methods for improving clean‐up efficiency and recovery; (ii) derivatization step for altering the chromatographic behavior of analytes and enhancing MS ionization efficiency; (iii) optimal LC–MS conditions and appropriate separation mechanism; and (iv) applications of other chromatographic methods, including miniaturized LC, 2D‐LC, 2D‐GC, and supercritical fluid chromatography. Altogether, this review is devoted to summarizing the recent technologies reported in the literature and providing new strategies for the detection of bioanalytes.

show abstract

“…[34] PYR is a fast-acting drug and it has a long biological half-life (13-17 days). [35] It is a useful molecule to delay the recrudescence of parasites and appearance of multidrug-resistance. Thus far, no case of drug-resistance induced by PYR has been observed.…”

Section: Pyronaridine As An Antimalarial Drugmentioning

confidence: 99%

Pyronaridine: An update of its pharmacological activities and mechanisms of action

Bailly

2020

Biopolymers

View full text Add to dashboard Cite

Pyronaridine (PYR) is an erythrocytic schizonticide with a potent antimalarial activity against multidrug-resistant Plasmodium. The drug is used in combination with artesunate for the treatment of uncomplicated P. falciparum malaria, in adults and children. The present review briefly retraces the discovery of PYR and recent antimalarial studies which has led to the approval of PYR/artesunate combination (Pyramax) by the European Medicines Agency to treat uncomplicated malaria worldwide. PYR Pyronaridine (PYR, Figure 1), initially known as "antimalaria drug 7351", is a benzo-naphthyridine derivative originally synthesized in 1979 [1] and developed in China from the early 1980s. [2][3][4] Rapidly, experimental studies demonstrated that this compound was more active than chloroquine against different isolates of Plasmodium falciparum, the malaria pathogen.

show abstract

Quantification of the antimalarial drug pyronaridine in whole blood using LC–MS/MS — Increased sensitivity resulting from reduced non-specific binding

Abstract: Graphical abstract

Cited by 8 publications

References 24 publications

Repurposing the antimalarial pyronaridine tetraphosphate to protect against Ebola virus infection

Repurposing the antimalarial pyronaridine tetraphosphate to protect against Ebola virus infection

Technologies to improve the sensitivity of existing chromatographic methods used for bioanalytical studies

Pyronaridine: An update of its pharmacological activities and mechanisms of action

Contact Info

Product

Resources

About