Determination of fenofibric acid in human plasma by ultra performance liquid chromatography–electrospray ionization mass spectrometry: application to a bioequivalence study

Dasandi, Bhavesh; Shah, Sanjay; Shivprakash,

doi:10.1002/bmc.1203

Cited by 20 publications

(19 citation statements)

References 13 publications

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“…The favorable pharmacokinetic properties of fenofibrate as well as its known safety and tolerability (3,28) suggest that it might have future clinical application. Its use may be restricted to combination with other established drugs such as artemisinin derivatives.…”

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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“…[12][13][14][15][16][17] A more recent study showed that the utilization of HPLC with tandem MS for the quantitation of fenofibric acid in plasma improved the LOQ, being 0.16 nmol/mL of plasma. 19) However, to our knowledge, the LOQ for fibric acids in liver samples have not been reported. Low LOQ in liver samples is important when Fibric acid (0.5, 2.5 or 20 nmol) was added to liver homogenates (10 mg of liver).…”

Section: Methods Validationmentioning

confidence: 84%

“…The high sensitivity to quantitate fibric acids without interference from liver components enable this method to be successfully applied to quantitate fibric acids in very small portions of the liver of rats treated with fibrates. A recently reported method, which employs HPLC with tandem MS detection, 19) seems to be more sensitive than our proposed method, but the method requires a tandem MS detector. The high sensitivity and simplicity of the presently described method to determine fibric acids should accelerate quantitative studies on the mechanisms underlying the bioactive action of fibric acids in tissues.…”

Section: Application Of the Methods To Actual Analysis Of Liver Samplesmentioning

confidence: 89%

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A Simple and Sensitive Method for the Determination of Fibric Acids in the Liver by Liquid Chromatography

Karahashi

Fukuhara

Hoshina

et al. 2014

Biological & Pharmaceutical Bulletin

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Fibrates are used in biochemical and pharmacological studies as bioactive tools. Nevertheless, most studies have lacked information concerning the concentrations of fibric acids working inside tissues because a simple and sensitive method is not available for their quantitation. This study aimed to develop a simple and sensitive bioanalytical method for the quantitation of clofibric, bezafibric and fenofibric acids in samples of very small portions of tissues. Fibric acids were extracted into n-hexane-ethyl acetate from tissue homogenates (10 mg of liver, kidney or muscle) or serum (100 µL) and were derivatized with 4-bromomethyl-6,7-dimethoxycoumarin, followed by HPLC with fluorescence detection. These compounds were separated isocratically on a reversed phase with acetonitrile-water. Standard analytical curves were linear over the concentration range of 0.2-20 nmol/10 mg of liver. Precision and accuracy were within acceptable limits. Recovery from liver homogenates ranged from 93.03 to 112.29%. This method enabled the quantitation of fibric acids in 10 mg of liver from rats treated with clofibric acid, bezafibric acid or fenofibrate. From these analytical data, it became clear that there was no large difference in ratio of acyl-CoA oxidase 1 (Acox1) mRNA level to fibric acid content in the liver among the three fibric acids, suggesting that these three fibric acids have similar potency to increase expression of the Acox1 gene, which is a target of peroxisome proliferatoractivated receptor α. Thus, the proposed method is a simple, sensitive and reliable tool for the quantitation of fibric acids working in vivo inside livers.Key words clofibric acid; bezafibric acid; fenofibric acid; HPLC quantitation; rat liverFibrates are known to increase low-density lipoprotein size, high-density lipoprotein synthesis, reverse cholesterol transport and insulin sensitivity, and suppress plasma triacylglycerol, and vascular and systemic inflammation. [1][2][3][4][5] Owing to these beneficial effects, fibrates are utilized as drugs for therapies of diseases, such as primary dyslipidemia, metabolic syndrome, type 2 diabetes, nonalcoholic fatty liver disease and atherosclerosis. Most of these actions of fibrates are considered to be mediated through peroxisome proliferatoractivated receptor α (PPARα), which then forms a heterodimer with retinoid X receptor (RXR); once activated, the PPARα/ RXR heterodimer binds to peroxisome proliferator response element, causing increased or decreased transcription of many genes in various tissues.6,7) Tissues with the highest expression of PPARα are liver, kidney, heart and brown adipose. Fatty acids and eicosanoids are the endogenous ligands of PPARα [7][8][9] ; before starting to function, fibrates, which are ester forms, have to be converted by hepatic esterases to fibric acids, carboxylic acid forms that are active forms as PPARα ligands. 7,10) Because of their potent activities, fibrates or fibric acids are widely used in biochemical and pharmacological studies as tools. Nevertheless, most...

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“…Fenofibrate is official in USP (11) and BP (12) but different methods have been cited in the literature for determination of fenofibrate involving HPLC-UV (13,14) and HPLC-MS (15), voltammetry (16) and differential pulse polarographic techniques (17). A stability indicating UPLC method for simultaneous determination of atorvastatin, fenofibrate and their impurities in tablets was developed and validated (14).…”

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confidence: 99%

High-performance liquid chromatography and derivative spectrophotometry for simultaneous determination of pravastatin and fenofibrate in the dosage form

et al. 2014

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High-performance liquid chromatography and derivative spectrophotometry for simultaneous determination of pravastatin and fenofibrate in the dosage formHigh performance liquid chromatography (HPLC) and second-order derivative spectrophotometry have been used for simultaneous determination of pravastatin (PS) and fenofibrate (FF) in pharmaceutical formulations. HPLC separation was performed on a phenyl HYPERSIL C18 column (125 mm × 4.6 mm i.d., 5 μm particle diameter) in the isocratic mode using a mobile phase acetonitrile/0.1 % diethyl amine (50:50, V/V, pH 4.5) pumped at a flow rate of 1.0 mL min -1. Measurement was made at 240 nm. Both drugs were well resolved on the stationary phase, with retention times of 2.15 and 5.79 min for PS and FF, respectively. Calibration curves were linear (R = 0.999 for PS and 0.996 for FF) in the concentration range of 5-50 and 20-200 μg mL -1 for PS and FF, respectively. Pravastatin and fenofibrate were quantitated in combined preparations also using the second-order derivative response at 237.6 and 295.1 nm for PS and FF, respectively. Calibration curves were linear, with the correlation coefficient R = 0.999 for pravastatin and fenofibrate, in the concentration range of 5-20 and 3-20 μg mL -1 for PS and FF, respectively. Both methods were fully validated and compared, the results confirmed that they were highly suitable for their intended purpose.

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Determination of fenofibric acid in human plasma by ultra performance liquid chromatography–electrospray ionization mass spectrometry: application to a bioequivalence study

Cited by 20 publications

References 13 publications

In Vitro Antimalarial Activity and Drug Interactions of Fenofibric Acid

In Vitro Antimalarial Activity and Drug Interactions of Fenofibric Acid

A Simple and Sensitive Method for the Determination of Fibric Acids in the Liver by Liquid Chromatography

High-performance liquid chromatography and derivative spectrophotometry for simultaneous determination of pravastatin and fenofibrate in the dosage form

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