High-performance liquid chromatographic procedure for the quantitation of propafenone in serum and tissues

Kannan, R.; Tidwell, Don; Singh, Bramah N.

doi:10.1016/s0378-4347(00)86152-6

Cited by 9 publications

(2 citation statements)

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“…During the last 4 years or so, the development of new, highly accurate techniques (22,(24)(25)(26)(27) for determination of blood levels of propafenone and its metabolites at concentrations as low as 5 ng/ml has greatly enhanced our understanding of the pharmacokinetic behavior of propafenone. However, it must be mentioned that the present state of our knowledge is incomplete.…”

Section: Clinical Pharmacokineticsmentioning

confidence: 99%

Propafenone

Karagueuzian

Peter

Mandel

1985

Cardiovascular Drug Reviews

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Section: Clinical Pharmacokineticsmentioning

confidence: 99%

Propafenone

Karagueuzian

Peter

Mandel

1985

Cardiovascular Drug Reviews

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“…Several chromatographic methods have been reported for the determination of propafenone and 5-OH-propafenone in biological matrices, including highperformance liquid chromatography (HPLC) [8][9][10][11][12][13][14][15]18 and gas chromatography. 16,17 For HPLC assays, different modes of detection have been employed, including UV [8][9][10][11][12][13][14][15] and fluorescence with precolumn derivatization. 18 Most of these methods have only been validated for propafenone, itself, or propafenone and 5-OH-propafenone.…”

Section: Introductionmentioning

confidence: 99%

A Rapid HPLC Assay for the Simultaneous Determination of Propafenone and Its Major Metabolites in Human Serum

Afshar

Rouini

2004

ANAL. SCI.

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Propafenone is a potent antiarrhythmic drug, which is widely used in the treatment of ventricular and supraventricular arrhythmias. 1 It blocks the fast inward sodium current in all cardiac and other excitable tissues, like the central nervous system. Propafenone also has some β-blocking action, much less than that of propranolol, and a weak calcium-channelblocking effect. 2 Propafenone undergoes extensive first-pass metabolism by the liver to form several metabolites. The main metabolic pathway of propafenone is ring hydroxylation to 5-OH-propafenone, being primarily mediated by CYP2D6. This pathway is polymorphically expressed in humans and is under genetic control, co-segregating with a well-described debrisoquine oxidation polymorphism, 3 such that poor metabolizers can be distinguished from extensive metabolizers. 4 An additional route of propafenone metabolism is N-demethylation to N-despropylpropafenone, which is primarily mediated via CYP3A4 and CYP1A2.5 Five hydroxy-propafenone has been shown to exert pharmacologic activity comparable to that of the parent drug. 6Although N-despropylpropafenone exerted antiarrhythmic activity in animal experiments, 7 relatively little is known about its pharmacokinetics and pharmacodynamics in humans. The metabolic pathway of propafenone is illustrated in Fig. 1.The specific metabolism of propafenone, its potential drug-drug interactions and its widespread use have stimulated efforts to develop routine assays for this drug and its metabolites in human serum. Several chromatographic methods have been reported for the determination of propafenone and 5-OH-propafenone in biological matrices, including highperformance liquid chromatography (HPLC) [8][9][10][11][12][13][14][15]18 and gas chromatography. 16,17 For HPLC assays, different modes of detection have been employed, including UV 8-15 and fluorescence with precolumn derivatization. 18Most of these methods have only been validated for propafenone, itself, or propafenone and 5-OH-propafenone. The resolution of N-despropylpropafenone, which is probably co-eluted under reported procedures, was rarely investigated.Among the methods described so far, only a few allow for the determination of the serum or plasma concentrations of propafenone and its main metabolites in a single run. A rapid and specific HPLC method has been developed and validated for the simultaneous determination of propafenone, an antiarrhythmic agent, and its major metabolites in human serum. The sample preparation was a simple deproteinization with a mixture of ZnSO4 and methanol, yielding almost 100% recoveries of three compounds. Separation was developed on a reverse-phase tracer excel C18 column (25 × 0.46 cm i.d., 5 µm), using an acetonitrilephosphate buffer gradient at a flow rate of 1.7 ml min -1 , and UV detection of 210 nm. The calibration curves were linear (r 2 > 0.999) in the concentration range of 10 -750 ng ml -1 . The lower limit of quantification was 10 ng ml -1 for all of the compounds studied. The within and between day precisions in th...

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The Use of High Performance Liquid Chromatography in Human Toxicology

Osselton¹

1986

Analytical Methods in Human Toxicology

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High-performance liquid chromatographic procedure for the quantitation of propafenone in serum and tissues

Cited by 9 publications

References 2 publications

Propafenone

Propafenone

A Rapid HPLC Assay for the Simultaneous Determination of Propafenone and Its Major Metabolites in Human Serum

The Use of High Performance Liquid Chromatography in Human Toxicology

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