Rapid, Sensitive and Validated Ultra‐Performance Liquid Chromatography/Mass Spectrometric Method for the Determination of Fenofibric Acid and its Application to Human Pharmacokinetic Study

Dubey, Sunil Kumar; Tomar, Manoj Singh; Patni, Anil; Khuroo, Arshad; Reyar, Simrit; Monif, Tausif

doi:10.1155/2010/726124

Cited by 5 publications

(5 citation statements)

References 6 publications

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“…Therefore, heat inactivation of pooled human plasma is required to reduce this growth-inhibitory activity prior to supplementation in culture medium. Plasma fenofibric acid is stable for up to 8 h at room temperature (17). Its stability in plasma at 50°C is, however, unknown.…”

Section: Discussionmentioning

confidence: 99%

In Vitro Antimalarial Activity and Drug Interactions of Fenofibric Acid

Wong¹,

Davis²

2012

Antimicrob Agents Chemother

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Plasmodium falciparum has developed resistance to most available treatments, underscoring the need for novel antimalarial drugs. Fibrates are lipid-modifying agents used to reduce morbidity and mortality associated with cardiovascular disease. They may have antimalarial activity through modulation of P-glycoprotein and ATP-binding cassette subfamily A member (ABC-1)-mediated nutrient transport and/or via a putative peroxisome proliferator-activated receptor alpha-like protein. We therefore examined in vitro antimalarial activities of fibrates and their interactions with chloroquine and dihydroartemisinin in chloroquine-sensitive (3D7) and chloroquine-resistant (W2mef) strains of P. falciparum using the conventional isotopic assay microtechnique. A bioassay was used to assess inhibition activities of human plasma after therapeutic fenofibrate doses. Fenofibric acid, the main metabolite of fenofibrate, was the most potent of the fibrates tested, with mean 50% inhibitory concentrations of 152 nM and 1,120 nM for chloroquine-sensitive and -resistant strains, respectively. No synergistic interaction between fibrates and chloroquine or dihydroartemisinin was observed. Plasma fenofibric acid concentrations, quantified by high-performance liquid chromatography in seven healthy volunteers after treatment (mean, 15.3 mg/liter, or 48 M), inhibited P. falciparum. BLAST analysis revealed the likely presence of an ABC-1 transporter homolog in P. falciparum. Our findings demonstrate that fenofibric acid has activity similar to the activities of conventional antimalarial drugs at concentrations well below those achieved after therapeutic doses. It may inhibit P. falciparum growth by inhibiting intracellular lipid transport.T he progressive increase in drug-resistant malaria, including the recent emergence of delayed clearance of Plasmodium falciparum after treatment with artemisinin derivatives (8,16,36), highlights the need for novel effective antimalarial drugs. One possible source is compounds which have been approved for other indications but which are found to have parasiticidal or diseasemodifying effects in malaria infection. Given prior detailed knowledge of their pharmacokinetic properties, safety, and tolerability, it is likely that such compounds can be fast-tracked through the usual drug development process. Examples that may prove to be pertinent to the treatment of human malaria are the glitazone drug rosiglitazone (4) and the 3-hydroxy-3-methyl-glutaryl coenzyme A reductase inhibitor atorvastatin (30,31,34).Fibrates such as gemfibrozil and fenofibrate are agonists of peroxisome proliferator-activated receptor alpha (PPAR␣) that are in relatively widespread clinical use as potent lipid-modifying drugs (13). The first study of fibrates in malaria found that clofibrate directly inhibited the development of parasitemia in P. berghei-infected mice (27). Subsequent studies have provided indirect evidence that fibrates might have therapeutic potential in malaria. One study showed that fenofibrate was the only member of ...

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Section: Discussionmentioning

confidence: 99%

In Vitro Antimalarial Activity and Drug Interactions of Fenofibric Acid

Wong¹,

Davis²

2012

Antimicrob Agents Chemother

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“…Fenofibric acid (2-[4'-(p-chlorobenzoyl) phenoxy]-2methylpropionic acid), the active metabolite of fenofibrate, produces reductions in total cholesterol, Low-Density Lipoprotein (LDL), apolipoprotein B, total triglycerides and triglyceride rich Very-Low-Density Lipoprotein (VLDL) in treated patients. In addition, treatment with FF results in increase in High Density Lipoprotein (HDL) [4] and apoproteins apoAI [5]. Fenofibrate (FF) as generic products has been very available recently to fulfill the demand of the global healthcare market.…”

Section: Development Of a Stability Indicating Uplc-ms/ms Methods For mentioning

confidence: 99%

“…(RIA), Gas Chromatography/Mass Spectrometry (GC/MS) and Liquid Chromatography (LC) with UV [5]. The key achievement of the current studies is the development of a sensitive method based on UPLC-MS/MS to quantitate the amount of active components such as FF in commercial pharmaceutical dosage formulation and spiked human plasma.…”

Section: Volume 1 | Issuementioning

confidence: 99%

Development of a Stability Indicating UPLC-MS/MS Method for Rapid and Reliable Determination of Fenofibrate in Marketed Product (Lypanthyl 200M) and Human Plasma

Sm¹,

Mohsin²,

Za³

2013

Journal of Pharmaceutics and Drug Development

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A reliable, fast, sensitive and selective Ultra Performance Liquid Chromatography-Tandem Mass Spectrometry (UPLC-MS/MS) method has been developed and validated for the determination of fenofibrate in marketed product (Lipanthyl) and human plasma. The chromatographic separation was performed on a reversed-phase Acquity®BEH C 18 column (1.7 μm particle size, 50 mm x 2.1 mm ID) with an isocratic elution profile and mobile phase consisting of methanol and water (80:20, %, v/v). To achieve optimum chromatographic condition the influence of mobile phase composition and flow rate was investigated. The total chromatographic analysis time was as short as 2 min. Detection and quantification of the analyzed drug sample were carried out with a triple quadrupole mass spectrometer using Electrospray Ionization (ESI) operating in positive ionization mode. The data acquisition was performed in Multiple Reactions Monitoring (MRM) mode. The method was validated over a concentration range of 0.5-200ng/ mL (r 2 =0.993, n=6). The selectivity, matrix effect, recovery, accuracy, precision, and stabilities were validated for determination of fenofibrate in human plasma. Analytical recoveries of extracted fenofibrate from plasma were more than 92%. The validation results showed that the proposed method was sensitive, economical and less toxic and it could successfully be applied for evaluation of pharmacokinetics of fenofibrate in animals.

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“…But the analysis time was not less than 9 min by LC-UV [24], and 1.5 min by LC-MS/MS [30], at the most sensitive wide dynamic range of 0.05-10 µg mL −1 [25]. Here, we have developed and validated a sensitive, fast, economic and easy analytical method for FFA determination in human plasma by LC-MS/MS and LC-UV, to investigate all study samples within a sensitive and wide dynamic calibration range of 0.05-20 µg mL −1 , as well as short run time of 0.5 min and 3.3 min by LC-MS/MS and LC-UV, respectively.…”

Section: Introductionmentioning

confidence: 99%

Determination of Fenofibric Acid in Human Plasma by LC–MS/MS and LC–UV

Arafat

Awwad

et al. 2016

Chromatographia

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systems during validation, and accuracies ranged between 91 and 112 %. Twenty-eight healthy adult subjects participated in this clinical study, and the pharmacokinetic parameters including coefficient of variation were calculated and discussed. A dramatic decrease in C max and AUC0-72 (3.63-and 1.85-fold, respectively) were observed for Lipanthyl™ MC under fasting conditions with more variable inter subject measurements comparing to the fed state.

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Rapid, Sensitive and Validated Ultra‐Performance Liquid Chromatography/Mass Spectrometric Method for the Determination of Fenofibric Acid and its Application to Human Pharmacokinetic Study

Cited by 5 publications

References 6 publications

In Vitro Antimalarial Activity and Drug Interactions of Fenofibric Acid

In Vitro Antimalarial Activity and Drug Interactions of Fenofibric Acid

Development of a Stability Indicating UPLC-MS/MS Method for Rapid and Reliable Determination of Fenofibrate in Marketed Product (Lypanthyl 200M) and Human Plasma

Determination of Fenofibric Acid in Human Plasma by LC–MS/MS and LC–UV

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