High-Performance Liquid Chromatographic Method for the Determination of Fenofibric Acid and Reduced Fenofibric Acid in Human Blood, Plasma and Urine

Abe, Sadahiro; Ono, Kaoru; Mogi, Masayuki; Hayashi, Tokishi

doi:10.1248/yakushi1947.118.10_447

Cited by 13 publications

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“…6). Abe et al demonstrated a reduced form of fenofibric acid, 2-{4-[(4-chlorophenyl)(hydroxy) methyl] phenoxy}-2-methylpropanoic acid, in plasma of rats treated with fenofibrate, 12) suggesting the possibility that the unknown fluorescent compound observed in the current study is the reduced form of fenofibric acid, which was formed in the liver. To verify the chemical structure of the unknown fluorescent compound on our chromatogram, we prepared chemically 2-{4-[(4-chlorophenyl)(hydroxy) methyl] phenoxy}-2-methylpropanoic acid from fenofibric acid, and confirmed that the retention time of the unknown fluorescent compound was completely the same as that of MDMC derivative of reduced form of fenofibric acid, on HPLC.…”

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

confidence: 48%

“…To obtain higher recovery values of analytes, however, the number of clean-up steps in a sample preparation procedure should be kept to a minimum. The extraction conditions of fibric acids into organic solvent that was employed in the present study were based on those developed previously by Abe et al, 12) who reported a method for the determination of fenofibric acid in plasma and urine by extraction with a mixed solvent of n-hexane-ethyl acetate (90 : 10, v/v) for the first extraction, and n-hexane- ethyl acetate (95 : 5, v/v) for the second extraction after backextraction with aqueous disodium hydrogen phosphate, followed by detection with HPLC-UV. In the study, they showed that the higher the proportion of ethyl acetate in a mixed solvent of n-hexane-ethyl acetate, the better the extractability of fenofibric acid from biological samples; in addition, the proportion of ethyl acetate in the extraction solvent should be kept lower than 10% to reduce the extraction of contaminants, which interfere with HPLC-UV analysis.…”

Section: Resultsmentioning

confidence: 99%

“…Previous studies employing HPLC with UV detection reported LOQ for fibric acids, with values ranging from 0.31 to 22.8 nmol/mL of plasma. [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.…”

Section: Methods Validationmentioning

confidence: 99%

“…[12][13][14][15][16][17] These methods were developed to determine the levels of fibric acids in plasma for clinical purposes, and are not always sensitive enough to quantitate fibric acids in the liver of rodents treated with these agents for biochemical or pharmacological studies. In this context, this study aimed to develop a simple and sensitive bioanalytical method for quantitation of clofibric, bezafibric and fenofibric acids in samples of very small portions of livers.…”

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

confidence: 48%

Section: Resultsmentioning

confidence: 99%

Section: Methods Validationmentioning

confidence: 99%

mentioning

confidence: 99%

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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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“…Liquid-liquid extraction procedure was used for the extraction of FA from the rat plasma. 16,17 The plasma samples were transferred into a series of 1.5 mL centrifugation tubes. A fixed amount of internal standard (fluvastatin) solution (25 µg/mL) was added to the plasma sample and vortexed.…”

Section: Uhplc Analysis Of Plasma Samplesmentioning

confidence: 99%

Development of self-nanoemulsifying drug delivery systems for the enhancement of solubility and oral bioavailability of fenofibrate, a poorly water-soluble drug

Kazi¹,

Alamri²,

Ahmad³

et al. 2016

IJN

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Background Self-nanoemulsifying drug delivery systems (SNEDDS) have become a popular formulation option as nanocarriers for poorly water-soluble drugs. The objective of this study was to investigate the factor that can influence the design of successful lipid formulation classification system (LFCS) Type III SNEDDS formulation and improve the oral bioavailability (BA) of fenofibrate. Materials and methods LFCS Type III SNEDDS were designed using various oils, water-soluble surfactants, and/or cosolvents (in considering the polarity of the lipids) for the model anticholesterol drug, fenofibrate. The developed SNEDDS were assessed visually and by measurement of the droplet size. Equilibrium solubility of fenofibrate in the SNEDDS was conducted to find out the maximum drug loading. Dynamic dispersion studies were carried out (1/100 dilution) in water to investigate how much drug stays in solution after aqueous dispersion of the formulation. The BA of SNEDDS formulation was evaluated in the rat. Results The results from the characterization and solubility studies showed that formulations containing mixed glycerides were highly efficient SNEDDS as they had higher solubility of the drug and produced nanosized droplets. The dispersion studies confirmed that SNEDDS (containing polar mixed glycerides) can retain >98% drug in solution for >24 hours in aqueous media. The in vivo pharmacokinetics parameters of SNEDDS formulation in comparison with pure drug showed significant increase in C max and AUC 0– t , ~78% and 67%, respectively. The oral BA of fenofibrate from SNEDDS in rats was ~1.7-fold enhanced as compared with the BA from pure drug. Conclusion Fenofibrate-loaded LFCS Type III SNEDDS formulations could be a potential oral pharmaceutical product for administering the poorly water-soluble drug, fenofibrate, with an enhanced oral BA.

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Comparisons of pharmacokinetics and NO‐releasing of nitrofibriate and fenofibrate after oral administration in rats

Yang

Cheng²,

Liu

et al. 2016

Biomedical Chromatography

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Nitrofibriate, a new compound of hypolipidemic, is modified based on fenofibrate. Both of them are used for prevention and treatment of cardiovascular diseases. In this study, an accurate and sensitive analytical method of reversed-phase high-performance liquid chromatography was developed to determine fenofibric acid, which is an active metabolite of both nitrofibriate and fenofibrate in rat plasma. This method was validated and successfully applied to pharmacokinetic study of nitrofibriate and fenofibrate after oral administration. The results suggested that the pharmacokinetic behavior of nitrofibriate followed a nonlinear process, while fenofibrate was linear, demonstrating that the two drugs were different in pharmacokinetic behaviors. Moreover, the effect of fenofibrate and nitrofibriate on releasing NO in rat serum was explored. This study showed that nitrofibriate, as a nitric oxide donor, could slowly release nitric oxide in vivo. This study provided a biopharmaceutical basis for further study of nitrofibriate.

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High-Performance Liquid Chromatographic Method for the Determination of Fenofibric Acid and Reduced Fenofibric Acid in Human Blood, Plasma and Urine

Cited by 13 publications

References 0 publications

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

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

Development of self-nanoemulsifying drug delivery systems for the enhancement of solubility and oral bioavailability of fenofibrate, a poorly water-soluble drug

Comparisons of pharmacokinetics and NO‐releasing of nitrofibriate and fenofibrate after oral administration in rats

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