High-performance liquid chromatographic separation and mass spectrometric identification of propafenone, 5-hydroxypropafenone and N-depropylpropafenone

Latini, Roberto; Sica, Anthony L.; Marchi, Stefano de; Chen, Z.M.; Gavinelli, Marco; Benfenati, Emilio

doi:10.1016/s0378-4347(00)81097-x

Cited by 12 publications

(6 citation statements)

References 4 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The other studies with active drugs (Marcolongo et al (1980), andWidmark (1982) Plasma concentrations of propafenone during chronic treatment with 300 mg three times daily, measured by high pressure liquid chromatography (Latini et al, 1988), ranged between 419 ng ml-'…”

mentioning

confidence: 99%

Propafenone in the treatment of chronic ventricular arrhythmias in a pregnant patient [letter]

Meniconi

Chiocchi

et al. 1988

Brit J Clinical Pharma

View full text Add to dashboard Cite

mentioning

confidence: 99%

Propafenone in the treatment of chronic ventricular arrhythmias in a pregnant patient [letter]

Meniconi

Chiocchi

et al. 1988

Brit J Clinical Pharma

View full text Add to dashboard Cite

“…A run time was set for 20 min to avoid a peak derived from serum contaminants at 19.3 min. The mobile phase containing 1‐pentanesulfonic acid as an ion–pair reagent provided a good resolution of propafenone and its metabolites without gradient elution or long run times required in the previous methods (Afshar & Rouini, ; Kates et al, ; Latini et al, ; Vozeh et al, ). The HPLC column was durable for routine analysis over 200 times.…”

Section: Resultsmentioning

confidence: 99%

“…The simultaneous determination of propafenone and its metabolites was carried out by HPLC (Afshar & Rouini, ; Kates, Yee, & Winkle, ; Latini et al, ; Vozeh, Haefeli, Ha, Vlcek, & Follath, ). These methods are inconvenient due to gradient elution, and long run times (>40 min).…”

Section: Introductionmentioning

confidence: 99%

Simultaneous determination of serum propafenone and its metabolites using high‐performance liquid chromatography

Shirayama

Doki

Sekiguchi

et al. 2017

Biomedical Chromatography

View full text Add to dashboard Cite

Propafenone, a class Ic antiarrhythmic agent, is metabolized to 5-hydroxypropafeone (5-OHP) and N-depropylpropafenone (NDPP). Simultaneous determination of serum propafenone and its metabolites was performed using HPLC equipped with a conventional octadecylsilyl silica column and ultraviolet detector. The wavelength was set at 250 nm. Propafenone and its metabolites in the serum were extracted using diethyl ether. The mobile phase solution, comprising 1-pentanesulfonic acid sodium salt (0.1 m), acetonitrile and acetic acid (280:185:2.5, v/v/v), was pumped at a flow rate of 1 mL/min. The recoveries of propafenone, 5-OHP and NDPP were greater than 85, 82 and 60%, respectively, with the coefficients of variation (CVs) less than 5.4, 1.9 and 2.9%, respectively. The calibration curves were linear for a concentration range of 12.5-1500 ng/mL for propafenone and 2-500 ng/mL for 5-OHP and NDPP (r > 0.999). CVs in the intraday assays were 1.0-3.8% for propafenone, 0.6-2.0% for 5-OHP and 0.6-1.7% for NDPP. CVs in interday assays were 1.3-7.7% for propafenone, 1.1-6.5% for 5-OHP and 5.4-8.0% for NDPP. The present HPLC method can be used to assess the disposition of propafenone and its metabolites for pharmacokinetic studies and therapeutic drug monitoring of propafenone.

show abstract

“…A small volume of serum is needed for sample preparation, and still the LOQ values (10 ng ml -1 ) are lower than the previously published methods, which were able to measure propafenone and its two metabolites. 19,20 The method also applies a simple and rapid sample treatment instead of rather laborious liquid-liquid or solid-phase extraction as part of the chromatographic procedure, yielding better recoveries, especially for N-despropylpropafenone, thereby saving time and expense for sample preparation. The method was found to be suitable to be currently used for pharmacokinetic studies in humans.…”

Section: Resultsmentioning

confidence: 99%

“…21 The major drawbacks of the mentioned methods are using complicated labor-and time-intensive sample-processing methods with several liquid-liquid extraction steps or solidphase extraction as sample preparation procedures, [19][20][21] long elution times, 19 poor sensitivity and recovery specially for N-despropylpropafenone. 20 This paper describes a rapid and specific HPLC method with UV detection for the simultaneous analysis of propafenone and its two major metabolites using direct protein precipitation. The developed method was successfully applied to assess the pharmacokinetics of propafenone and its two major metabolites following the oral administration of a single 300 mg dose of propafenone hydrochloride to three healthy male volunteers.…”

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.

View full text Add to dashboard Cite

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...

show abstract

High-performance liquid chromatographic separation and mass spectrometric identification of propafenone, 5-hydroxypropafenone and N-depropylpropafenone

Cited by 12 publications

References 4 publications

Propafenone in the treatment of chronic ventricular arrhythmias in a pregnant patient [letter]

Propafenone in the treatment of chronic ventricular arrhythmias in a pregnant patient [letter]

Simultaneous determination of serum propafenone and its metabolites using high‐performance liquid chromatography

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

Contact Info

Product

Resources

About