Propranolol plasma monitoring in children submitted to surgery of tetralogy of Fallot by a micromethod using high performance liquid chromatography.
OBJECTIVE
To evaluate the analytical micromethod using liquid chromatography for the quantification of propranolol in children submitted to surgery of tetralogy of Fallot (TLF).


METHODS
Only 0.2 mL of plasma is required for the assay. Peaks eluted at 8.4 (Propranolol) and 17.5 min (verapamil, internal standard) from a C18 column, with a mobile phase 0.1 M acetate buffer, pH 5.0, and acetonitrile (60:40, v/v) at flow rate 0.7 mL/min, detected at 290 nm (excitation) and 358 nm (emission). Surgery was started 776 min of drug administration (8.7 mg, mean); seven blood samples were collected from six patients (4M/2F; 2.1 yrs;11.5 kg; 0.80 m; 18.9 kg/m(2)).


RESULTS
Confidence limits of the method showed high selectivity and recovery, sensitivity of 0.02ng/mL, good linearity (0.05-1000 ng/mL), precision of 8.6% and accuracy of 3.1%. The mean duration of surgery was 283.2 min, with the patients remaining under cardiopulmonary bypass (CPB) for 114 min. A declining curve of propranolol plasma concentration was obtained after the last dose in the night that preceded the day of surgery. Plasma concentration also was normalized with hematocrit due to the hemodilution caused by the CPB procedure. On the other hand a decrease on drug plasma concentration was obtained between periods, the beginning of surgery to the postoperative day 2 (7.09 ng/mL and 0.05 ng/mL, p<0.05 respectively) and from the end of CPB to the postoperative day 2 (2.79 ng/mL e 0.05 ng/mL, p<0.05).


CONCLUSIONS
Propranolol monitoring of plasma concentrations of children (TLF) normalized after the last preoperative dose revealed a decline from the beginning of surgery to the second postoperative day, suggesting that, once redistribution was restored, propranolol washout was complete.
Sanches
Cristina
C
School of Pharmaceutical Sciences, University of Sao Paulo Medical School, Sao Paulo, SP, Brazil.
Galas
Filomena R B G
FR
Silva
Anne G O de M
AG
Carmona
Maria Jose C
MJ
Auler
José Otavio
JO
Santos
Silvia Regina Cavani Jorge
SR
D002675:Child, Preschool; D002851:Chromatography, High Pressure Liquid; D016903:Drug Monitoring / Q000379:methods; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D008832:Microchemistry / Q000379:methods*; D019990:Perioperative Care; D011433:Propranolol / Q000097:blood* / Q000493:pharmacokinetics / Q000627:therapeutic use; D012015:Reference Standards; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013771:Tetralogy of Fallot / Q000097:blood / Q000601:surgery*; D014665:Vasodilator Agents / Q000097:blood* / Q000493:pharmacokinetics / Q000627:therapeutic use
D014665:Vasodilator Agents; D011433:Propranolol