RESUMO
PURPOSE: The aim was to prepare and evaluate unitary doses of propafenone (UDP) used in children with supraventricular tachycardia. METHODS: UDP were prepared from four brands of tablets at doses of propafenone, 11, 25 and 90 mg, used in the Cardiology Service of this Institute. The stability of doses was determined at 20±5°C and 40°C for up to day 30. Besides, a weight variation test was performed. Plasma levels of propafenone were determined at steady state in 3 children diagnosed with supraventricular tachycardia under treatment with UDP. Concentrations of drug in blood were measured using a high pressure liquid chromatography method, previously validated. RESULTS: The stability of UDP, showed no significant statistical differences (p > 0.05) between doses or brands up to day 30, at both temperatures. The coefficient of variation from the weight variation was less than 6%. The plasma levels of propafenone at steady state were: patient 1, 31.57 ng/ml; patient 2, 226.46 ng/ml; and patient 3, 221.29 ng/ml. CONCLUSIONS: The actual administered dose for the patients could vary up to 6%, and doses prepared from different brands of tablets remain stables for up to day 30 at both temperatures. UDP is a temporal, safe and alternative option when pediatrics formulation of this drug is lacking.
Assuntos
Antiarrítmicos/uso terapêutico , Propafenona/administração & dosagem , Taquicardia Supraventricular/tratamento farmacológico , Criança , Humanos , Projetos Piloto , Propafenona/sangueRESUMO
HPLC on chiral stationary phases has been used for the enantioselective assay of propafenone (PPF), 5-hydroxypropafenone (PPF-50H) and N-despropylpropafenone (PPF-NOR) enantiomers. The results obtained on Chiralpak AD column showed that it is useful for the resolution of PPF and of its main metabolites, although the peaks obtained for PPF-NOR were not symmetrical under the conditions investigated. This column and circular dichroism-based detection system were used to determine the absolute configuration of the eluates. Furthermore, the influence of the mobile phase composition on the resolution of PPF and of its main metabolites was investigated on cellulose derivatives (Chiralcel OD-H and Chiralcel OD-R) and protein (Chiral AGP and Ultron ES-OVM)-based chiral stationary phases. The enantiomers of PPF were resolved on all the columns, except for the Ultron ES-OVM. This column, the Chiralpak AD and the Chiralcel OD-H columns were suitable for the resolution of the PPF-50H enantiomers. The PPF-NOR enantiomers were resolved on the Chiralpak AD, Chiral AGP and Chiralcel OD-R columns.
Assuntos
Antiarrítmicos/sangue , Propafenona/sangue , Celulose/química , Cromatografia Líquida de Alta Pressão , Dicroísmo Circular , Humanos , Ovomucina/química , Polissacarídeos/química , Proteínas/química , EstereoisomerismoRESUMO
An enantioselective liquid chromatography method was developed for the simultaneous determination of propafenone (PPF) and 5-hydroxypropafenone (PPF-5OH) enantiomers in plasma. After liquid liquid extraction with dichloromethane, the enantiomers were resolved on a Chiralpak AD column using hexane-ethanol (88:12, v/v) plus 0.1% diethylamine as the mobile phase and monitored at 315 nm. Under these conditions the enantiomeric fractions of the drug and of its metabolite were analysed within 20 min. The extraction procedure resulted in absolute recoveries of 62.9 and 61.3% for (R)- and (S)-PPF, respectively, and of 57.6 and 56.5% for (R)- and (S)-PPF-5OH, respectively. This procedure was efficient in removing endogenous interferents as well the interference of an other PPF metabolite, N-despropylpropafenone (PPF-NOR). The calibration curves were linear over the concentration range 25-1250 ng/ml. Low values of the coefficients of variation were demonstrated for both within-day and between day assays. The method described in this paper allows the determination of PPF and PPF-5OH enantiomers at plasma levels as low as 25 ng/ml and can be used in clinical pharmacokinetic studies.
Assuntos
Antiarrítmicos/sangue , Propafenona/análogos & derivados , Amilose , Antiarrítmicos/farmacocinética , Calibragem , Cromatografia Líquida de Alta Pressão , Humanos , Cloreto de Metileno , Propafenona/sangue , Propafenona/farmacocinética , Reprodutibilidade dos Testes , Soluções , EstereoisomerismoRESUMO
We present a method for the enantioselective analysis of propafenone in human plasma for application in clinical pharmacokinetic studies. Propafenone enantiomers were resolved on a 10-microm Chiralcel OD-R column (250 x 4.6 mm I.D.) after solid-phase extraction using disposable solid-phase extraction tubes (RP-18). The mobile phase used for the resolution of propafenone enantiomers and the internal standard propranolol was 0.25 M sodium perchlorate (pH 4.0)-acetonitrile (60:40, v/v), at a flow-rate of 0.7 ml/min. The method showed a mean recovery of 99.9% for (S)-propafenone and 100.5% for (R)-propafenone, and the coefficients of variation obtained in the precision and accuracy study were below 10%. The proposed method presented quantitation limits of 25 ng/ml and was linear up to a concentration of 5000 ng/ml of each enantiomer.