Determination of unbound piperaquine in human plasma by ultra-high performance liquid chromatography tandem mass spectrometry

Huang, Liusheng; Sok, Vong; Aslam-Mir, Usman; Marzan, Florence; Whalen, Meghan; Rosenthal, Philip J.; Aweeka, Francesca

doi:10.1016/j.jcoa.2022.100042

Cited by 6 publications

(2 citation statements)

References 17 publications

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“…The drug‒drug interactions (DDIs), pharmacodynamics, and pharmacokinetic properties of a drug are closely related to its reversible binding to plasma or serum proteins. Variations in plasma protein content may affect the pharmacokinetics exposure of unbound drugs, leading to alterations in clinical outcomes ( Huang et al, 2022 ). The plasma protein binding rate for glytrexate in human plasma was higher than that in rat plasma, and the plasma protein binding rate in both rats and humans was less than 30%, as shown in Table 5 , indicating that the compound binds less to plasma proteins.…”

Section: Discussionmentioning

confidence: 99%

Pharmacokinetics, bioavailability, and plasma protein binding study of glytrexate, a novel multitarget antifolate

Xiang

Wu²,

Wang³

et al. 2022

Front. Pharmacol.

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Glytrexate, developed by our team, as a novel multitarget folate antagonist, has inhibitory effects on a variety of cancer cell types, especially KB tumor cells (IC50 0.078 nM), and thus has antitumor drug development prospects. However, its pharmacokinetics and plasma protein binding properties remain unknown. In this study a selective and sensitive liquid chromatography-tandem mass spectrometry (LC‒MS/MS) method was developed and verified to facilitate biological analysis. The bioanalysis method was applied to evaluate the stability, plasma protein binding, and pharmacokinetics of glytrexate. Glytrexate is more stable in human plasma than in rat plasma and in human liver microsomes. The binding of glytrexate to human plasma proteins was higher than that to rat plasma proteins, both of which were less than 30%, suggesting that glytrexate may be at a higher concentration at the pharmacologic target receptor(s) in tissues. Pharmacokinetic characteristics were determined by noncompartmental analysis after administration of single oral (12.5, 25 and 50 mg/kg) and intravenous (2 mg/kg) doses in rats. According to the rat oral pharmacokinetic characteristics, glytrexate had linear dynamics in a dose range of 12.5–50 mg/kg and a poor oral bioavailability of 0.57–1.15%. The investigation revealed that the intravenous half-life, AUC, and Cmax of glytrexate were higher than those of pemetrexed. Pemetrexed is generally produced as an injection preparation. This provides ideas for the development of glytrexate formulations. Therefore, glytrexate injection has clinical application prospects compared to oral administration. This study provides a basis for further investigations into the pharmacological effects and clinical uses of glytrexate.

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Section: Discussionmentioning

confidence: 99%

Pharmacokinetics, bioavailability, and plasma protein binding study of glytrexate, a novel multitarget antifolate

Xiang

Wu²,

Wang³

et al. 2022

Front. Pharmacol.

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“…Various techniques were documented for the determination of the investigated pharmaceutical compounds and their formulations, encompassing UV spectrophotometric methods, HPTLC and HPLC methods [28][29][30][31][32][33][34][35][36][37][38]. There are limited research articles reported for the quantification of various antimalarial drugs by using the quality-by-design methodology [39].…”

Section: Introductionmentioning

confidence: 99%

A Novel Approach to AQbD-Assisted Green and Robust UPLC Method for the Determination of Selected Aminoquinoline Antimalarial Drugs: Assessment of Green Method

CHEERLA,

RAO

2023

ajc

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Greening analytical procedures have gained popularity in the area of pharmaceutical industries in order to safeguard the environment. In this study, an innovative methodology by integrating analytical quality-by-design (AQbD) along with Green Chemistry concepts with a systematic approach has been used to develop an environmentally-friendly and more robust ultra performance liquid chromatography (UPLC) method for the determination of three selected aminoquinoline antimalarial drugs namely amodiaquine hydrochloride (AMD), chloroquine phosphate (CHQ) and piperaquine phosphate (PPQ). An environmentally benign solvent ethanol has been chosen as an alternative to the commonly used acetonitrile and methanol, which are widely used. Based on the comprehensive risk analysis, the critical method parameters (CMP’s) that affect the critical method attributes (CMA’s) have been identified and the final method parameters were further optimized with the help of a full factorial design and the design of experiments (DOE), established the “design space”(DS) and identified the “method-operable-design-region (MODR) for the developed method. Achieved the separation with the use of an Acquity- UPLC BEH Shield RP-18 (100 mm × 2.1 mm), 1.7 μm column by using an isocratic elution of mobile phase containing 0.1% trifluoroacetic acid in water, ethanol in a mixture of 90:10% v/v and maintained a flow rate of 0.2 mL min-1 and the column oven temperature was 40 ºC and the UV detection wavelength of 225 nm was employed. A statistical tool Analysis of Variance (ANNOVA) has been used to assess the model’s statistical significance and found that the model’s p-values is < 0.00005 and its lack of fi is > 0.05 respectively, which demonstrates that the selected model is the most appropriate predictive tool for the analyzed responses R1 & R2 (i.e. peak resolutions R1 & R2). The proposed method’s linearity, accuracy & precision studies has been successfully validated in compliance with USP <1225> and ICH Q2 (R1) guidelines. Further assessed the proposed method’s greenness using various green evaluation tools such as: “complex green analytical procedure index”-cGAPI, “analytical greenness”-AGREE, “analytical method green score”-AMGS and found acceptable results. This novel AQbD-assisted eco-friendly analytical method for the quantification of AMD, CHQ & PPQ in bulk drugs (APIs) or finished dosage forms is simple, rapid, precise and accurate, robust and environmentally benign.

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The effect of malaria-induced alteration of metabolism on piperaquine disposition in Plasmodium yoelii infected mice and predicted in malaria patients

Xie,

Zhang,

Lin

et al. 2024

International Journal of Antimicrobial Agents

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Determination of unbound piperaquine in human plasma by ultra-high performance liquid chromatography tandem mass spectrometry

Cited by 6 publications

References 17 publications

Pharmacokinetics, bioavailability, and plasma protein binding study of glytrexate, a novel multitarget antifolate

Pharmacokinetics, bioavailability, and plasma protein binding study of glytrexate, a novel multitarget antifolate

A Novel Approach to AQbD-Assisted Green and Robust UPLC Method for the Determination of Selected Aminoquinoline Antimalarial Drugs: Assessment of Green Method

The effect of malaria-induced alteration of metabolism on piperaquine disposition in Plasmodium yoelii infected mice and predicted in malaria patients

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