Propafenone hydrochloride

Chamical Nama 2 -(2-Hydroxy-3-propylaminopropoxy)-3-phenylpropiophenone hydrochloride 

3-epoxypropoxy)-3-phenylpropiophenone — 24.B g of the sodium salt of 2 -hydroxy-3-phenylpropiophenone were mixed with 40 cm of 1-chloro-2,3-epoxypropane (epichlorohydrin) and the mixture heated on a boiling water bath while stirring, using a reflux condenser. The initially pasty-to-solid mixture liquefied after about 2 hours, sodium chloride separating out. Thereafter it was heated for a further 2 hours while stirring, using a reflux condenser. The mixture was then allowed to cool and subsequently freed, by filtration, from the sodium chloride formed. The filtrate was concentrated in vacuo, and the excess 1-chloro-2,3-epoxy-propane thus separated from the desired 2 -(2,3-epoxypropoxy)-3-phenylpropiophenone. The latter remained as a yellowish oil which solidified in the cold, but did not crystallize. Purification of the intermediate product, by distillation in vacuo, was not necessary, particularly as the substance only boiled at a temperature of 2B0°C/12 mm Hg and at the same time decomposed.  

Approximately 25 g (66.2% of theory) of a white crystalline substance were obtained. The melting point of the hydrochloride was 173°C to 174°C. 

Sachse, R. British Patent 1,307,455 February 21,1973 assigned to Helopharm W. Patrick Co. K.G. 

Trade Name Manufacturer Country Year Introduced 

2 -(2-hydroxy-3-propylaminopropoxy)-3-phenylpropiophenone hydrochloride - The above product was treated with 20 cm of n-propylamine and the mixture warmed on a water bath for approximately 4 hours, while stirring, using a reflux condenser. Thereafter, the excess n-propylamine was distilled off. On cooling, the residue solidified to give a viscous yellow mass. 20 cm of 1M aqueous hydrochloric acid were added to it, and the whole was boiled for 1 hour under reflux, while stirring. The mixture was then poured into a suitable vessel and allowed to crystallize at room temperature. The crude product was drained thoroughly by suction and subsequently crystallized from a mixture of acetone/methanol (80 20, v/v). 

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Propafenone. Propafenone hydrochloride, an arylketone, is stmcturaHy similar to the P-adrenoceptor blocking agents. It has been in use in the former West Germany since 1977 and was introduced in the United States in 1990. Its effects may result from a combination of weak calcium channel blocking, weak nonselective -adrenoceptor blocking, and sodium channel blocking activity. Propafenone is effective in treating supraventricular tachyarrhythmias, ventricular ectopic beats, and ventricular arrhythmias. It is the most frequendy prescribed medication for ventricular arrhythmias in Europe (32). 

Class I, Type 1C Antiarrhythmics flecainide acetate propafenone hydrochloride... 

Propafenone Hydrochloride Methanol, Acetone 30 M X 0.5.3 mm I D. fused Silica column with Helium 40-240 Rapidly FID None USP (24, p. 1414)... 

Arythmol (Propafenone hydrochloride). Abbott Laboratories Ltd. UK Summary of product clwacteristics, December 2001. 

Iron, iodine, vitamin A Propafenone hydrochloride and tocopheryl acetate Glucose solution... 

Propafenone, l- 2-[2-hydroxy-3-(propylamino)propoxy]phenyl -3-phenylpropan-l-one, is a conunonly used sodium and potassium channel blocker for the treatment of ventricular tachycardia and atrial fibrillation [15]. Propafenone hydrochloride is a class IC antiarrhy tmic agent that shows structural similarity and activity related to p-adrenoly tic agents. The drug is efficacious in suppressing supraventricular and ventricular rhythm disorders [15] (Figure 14.12). 

The TLC method was developed for the determination of the photodegradated propafenone hydrochloride [15]. 

Good separation of propafenone hydrochloride from the degradation products was obtained and the received values of retardation factors were as follows for propafenone hydrochloride Rp 0.64, and for the degradation products 0.43, 0.82, and 0.88. The elaborated method was validated using ICH guidelines. The linear calibration function was obtained with respect to the peak area in the concentration range of 0.1-3.2 j,g spor, respectively. The limits of detection and quantification were, respectively, 0.02 and 0.08 pg per band. 

The degradation of propafenone hydrochloride, reaching 38.5%, was observed because of exposure to UV irradiation. 

The identified photolytic degradation products of propafenone hydrochloride are benzoic acid/methyl ester (tn/z = 136.0 amu), 2H-l-benzopyran/3,4-dihydro-2-phenyl (tn/z = 210.1 amu), and l-(2-hydroxyphenyl)-3-phenyl-l-propanone( i/z = 226.1 amu). 

Pietras, R., Kowalczuk, D., Rutkowska, E., Komsta, L., and Gumieniczek, A. 2014. Validated stability-indicating HPTLC method for the determination of propafenone hydrochloride in tablets and the GC-MS identification of its degradation products, J. Liq. Chromatogr. Relat. TechnoL, 37 2942-2955. 

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