Monitoramento do propranolol em crianças submetidas a correção cirúrgica da Tetralogia de Fallot através de cromatografia líquida de alta eficiência: fluorescência

Abstract

The objective of the present study was to develop a simple and sensitive micromethod for the quantification of propranolol in plasma using HPLC-fluorescence for drug plasma concentration monitoring during the washout. Only 200mcL of biological sample was necessary. The retention times of the drug and its internal standard (verapamil) were 8.4 and 17.5 min, respectively, using a C18 reverse-phase column and a mobile phase consisting of 0.1 M acetate buffer, pH 5.0, and acetonitrile (60:40, v;/v), with detection at λex = 290 nm and λem = 358 nm in an isocratic elution system. Validation of this analytical method showed that it was highly sensitive, with a detection limit of 0.02 ng/ml, linearity in the range of 0.05 to 1000 ng/mL, and intraand inter-day precision of 4.7 and 8.6%, respectively. In addition, the method showed good accuracy and high selectivity. Analytical method validated showed high sensitivity for the quantification of propranolol; then this method was applied to quantify propranolol in plasma of children during the surgery for correction of tetralogy of Fallot including a followup at the first and second days of the intervention. The plasma propranolol concentrations, hematocrit normalized, after the last preoperative dose, expressed as medians, were: 7.09 ng/mL at the beginning of surgery, 2.69 ng/mL at the beginning of cardiopulmonary bypass (CPB), 1,14 ng/mL during CPB, 2,79 ng/mL after CPB, and 2.70 ng/mL at the end of surgery. Median of late postoperative propranolol concentrations were 0,63 ng/mL on postoperative day 1 and 0.03 ng/mL on day 2. A significant decline on the normalized propranolol concentration was observed between the beginning of surgery and the beginning of CPB. In addition, in spite of the prolonged mean residence time of 35.8 hours, the propranolol concentrations decreased significantly at the postoperative period on day 1 up to day 2, indicating that, once the redistribution is restored, the washout of drug was completed,.